erbitux

Erbitux recognized by ASCO as a 2009 major cancer advance as first SCCHN treatment to improve survival in 30 years

Source: www.vwd.de
Author: press release

The American Society of Clinical Oncology (ASCO) has once again recognized Erbitux® (cetuximab) as one of the major clinical cancer advances of 2009. This year Erbitux was selected by ASCO for providing the first significant increase in survival for 30 years in the treatment of patients with first-line recurrent and/or metastatic squamous cell carcinoma of the head and neck(SCCHN).1

ASCO Clinical Advances Report1
The ASCO report, ‘Clinical Cancer Advances 2009: Major Research Advances in Cancer Treatment, Prevention and Screening’, published this week in the Journal of Clinical Oncology, is an independent assessment of the most significant clinical cancer research studies of the past year.

Erbitux was singled out for the pivotal first-line SCCHN study, the first randomized trial in 30 years to identify a regimen that increases survival for patients with recurrent and/or metastatic SCCHN. The report commented that, “The ability to improve overall survival with chemotherapy has proven elusive over the last 30 years in several randomized trials comparing different chemotherapy regimens in this setting. Thus, the results of this trial are particularly noteworthy and are changing clinical practice.”

This is the second consecutive year that Erbitux has featured in the ASCO ‘Advances’ list.3 In 2008 it was recognized for extending survival in the first-line treatment of NSCLC and for the role of KRAS tumor status in predicting whether patients with newly diagnosed metastatic colorectal cancer will respond to Erbitux.2

“Merck Serono is honored that Erbitux is recognized by ASCO two years in a row, and across three different disease areas – colorectal cancer, lung cancer and now head and neck cancer, as a major clinical advance,” commented Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “This latest acknowledgement from ASCO is a tribute to the role Erbitux now plays as a gold standard therapy in first-line recurrent and/or metastatic SCCHN”.

The study demonstrated that SCCHN patients treated with Erbitux plus chemotherapy experienced the following improvements, compared to chemotherapy alone:3
– Median overall survival (OS) increased by nearly 3 months (10.1 vs. 7.4 months; p=0.04), equating to a 20% reduction in the risk of death (Hazard Ratio [HR] 0.80) during the study period
– 46% increase in median progression-free survival (5.6 vs. 3.3 months; p <0.001)
– Almost doubling of response rate (36% vs. 20%; p<0.001)
– Based on the EXTREME study, the ESMO Guidelines Working Group earlier this year recommended Erbitux as the only treatment with a grade of recommendation ‘A’ and level of evidence ’I’^4

Long-Term Survival Results in Locally Advanced SCCHN
Also this week, the 5-year survival data from the Bonner trial for Erbitux in locally advanced (LA) SCCHN were published in the Lancet Oncology. The Phase III Bonner trial formed the basis for the initial Erbitux LA SCCHN license, granted in Europe in 2006. This new long-term analysis provides further support for the combination of Erbitux and radiotherapy in the treatment of LA SCCHN, demonstrating:^5
– Almost half of patients receiving Erbitux plus radiotherapy are still alive at 5 years – in contrast to only one third of patients receiving  radiotherapy alone (45.6% vs. 36.4%; p=0.018)
– Adding Erbitux to radiotherapy leads to a sustained survival benefit (OS
49.0 vs. 29.3 months; HR 0.725; p=0.018)
– The development of prominent skin rash is associated with an additional survival benefit leading to a reduction in the risk of death of 51%

Head and Neck Cancer
Head and neck cancer includes cancers of the tongue, mouth, salivary glands, pharynx, larynx, sinuses and other sites located in the head and neck area. It is estimated that there are around 143,000 new cases of head and neck cancer and more than 68,000 deaths due to the disease in Europe each year.^6 About 90% of head and neck cancers are of the squamous cell variety^7 and nearly all express the epidermal growth factor receptor which is critical for tumor growth.8 About 40% of patients with head and neck cancer have recurrent and/or metastatic SCCHN.9 At least 75% of all head and neck cancers are attributed to two major risk factors, smoking and alcohol consumption.10

References
1 . Petrelli NJ, et al. J Clin Oncol 2009;ePub ahead of print November 6, 2009.
2 . Winer E, et al. J Clin Oncol 2009;27(5):812-26.
3 . Vermorken JB, et al. N Engl J Med 2008;359:1116-27.
4 . Licitra L, & Felip E. Ann Oncol 2009;20(Suppl 4):iv121–iv122.
5 . Bonner J, et al. Lancet Oncol 2009;ePub ahead of print November 7, 2009.
6 . GLOBOCAN 2002 (www-dep.iarc.fr), accessed November 2009.
7 . Vermorken J. Ann Oncol 2005;16(Suppl 2):ii258-ii264.
8 . Grandis JR & Tweardy DJ. Cancer Res 1993;53(15):3579-84.
9 . Lefebvre J-L. Ann Oncol 2005;16(Suppl 6):vi7-vi12.
10 . Hashibe M, et al. J Natl Inst 2007;99:777-89

November, 2009|Oral Cancer News|

Report highlights cancer advances

Source: www.medpagetoday.com
Author: Charles Bankhead, Staff Writer, MedPage Today

As the war on cancer enters its fifth decade, 51 studies stood out as examples of progress that occurred in the past year, as determined by the American Society of Clinical Oncology (ASCO) and reported in “Clinical Cancer Advances 2009.”

Reflecting input from specialists throughout the field, the ASCO annual report highlights research developments for nine types of cancer, as well as cancer disparities, quality of life and quality of care, and cancer prevention and screening.

“As this report demonstrates — and as history shows — investment in clinical cancer research pays off,” ASCO president Douglas Blayney, MD, of the University of Michigan in Ann Arbor, said in a statement included in the report.

“Since 1990, cancer mortality rates have declined by 15%. Today, two-thirds of patients survive at least five years after diagnosis, compared to just half of patients 40 years ago.”

“Thanks to basic research advances, we are entering an era of personalized cancer medicine, in which treatment is tailored to the unique genetics of the individual,” Blayney added.

The entire report appears online in the Journal of Clinical Oncology, but here is a summary of developments related to some of the most common cancers.

In an attempt to provide context and a diversity of viewpoints, MedPage Today, in collaboration with ABC News, solicited comments from cancer specialists who were not involved in developing the ASCO publication. As appropriate, their views are included with the review of cancer research highlights.

Head and Neck Cancers
Adding the targeted agent cetuximab (Erbitux) to chemotherapy significantly improved progression-free survival and overall survival in patients with untreated recurrent or metastatic head and neck cancer. Noting failure of several previous trials to demonstrate a survival advantage with chemotherapy, ASCO cancer specialists said the findings should change clinical practice.

Another targeted agent, gefitinib (Iressa), did not improve survival compared with methotrexate in patients with recurrent squamous-cell carcinoma of the head and neck.

The practice of “re-irradiation” following chemoradiation therapy reduced the risk of local recurrence but did not improve survival in patients with adverse-feature head and neck cancer. Additional radiation reduced the risk of recurrence by 50%, but patients did not live any longer than those who received conventional chemoradiation followed by active surveillance. Moreover, re-irradiation led to a fourfold increase in the incidence of grade 3-4 toxicity.

Breast Cancer
Results of a large, randomized clinical trial settled a longstanding debate about the superiority of a standard three-drug chemotherapy regimen versus monotherapy with capecitabine (Xeloda) for breast cancer in women 65 and older. Women randomized to the single agent had a twofold increase in the risk of relapse and death compared with women who received cyclophosphamide, methotrexate/fluorouracil, and doxorubicin. Three-year relapse-free survival was 68% with monotherapy and 85% with the combination. Overall survival was 86% with monotherapy versus 91% with the combination.

Stefan Gluck, MD, of the University of Miami, had a different take on the study results. Acknowledging the better survival in the capecitabine arm, Gluck took issue with the trial’s clinical significance. “This is not major research. It did not change practice, did not change outcome, did not change toxicity, and did not change cost.”

On the other hand, Hyman Muss, MD, of the University of North Carolina in Chapel Hill, cited the trial results as an example of clinical research that has influenced his clinical practice in the past year.

Two studies provided evidence that the investigational class of agents known as poly(ADP-ribose) polymerase (PARP) inhibitors has efficacy in so-called triple-negative breast cancer. The agents block cancer cells’ ability to repair DNA damage, including damage inflicted by chemotherapy.

Seconding the ASCO specialists’ view, Gluck said the investigation of PARP inhibitors is a major accomplishment in the field of breast cancer.

Michael J. Fisch, MD, of the University of Texas M.D. Anderson Cancer Center in Houston, agreed, calling PARP inhibitors “a new category of treatment for a very difficult-to-treat subset” of breast cancer patients.

Gastrointestinal Cancers
A large Phase III clinical trial of patients with HER2-positive gastric cancer had a significant reduction in the risk of death when treated with trastuzumab (Herceptin) plus standard chemotherapy compared with chemotherapy alone. Treatment with trastuzumab did not increase the risk of symptomatic congestive heart failure.

British investigators reported data from a trial that established the first standard of care for biliary tract cancer. The combination of gemcitabine (Gemzar) and cisplatin significantly improved progression-free survival and overall survival compared with gemcitabine alone.

Adding the targeted agent bevacizumab (Avastin) to standard chemotherapy did not reduce the risk of recurrence in early-stage colon cancer. The three-year disease-free survival was 77.4% with the investigational therapy and 75.5% with standard chemotherapy.

M.D. Anderson’s Fisch said oncologists had mixed reactions to the bevacizumab findings.

“On one hand, oncologists always want to see positive findings about new therapies, but some oncologists also noted that the overall healthcare expense associated with a positive finding on this particular study may have created some real dilemmas,” he said.

Genitourinary Cancers
Men with early-stage prostate cancer had about a 29% reduction in the risk of metastasis and 28% improvement in survival when they received adjuvant radiation therapy following radical prostatectomy. ASCO cancer specialists called the trial a “practice-changing study.”

Two different drugs received FDA approval for treatment of renal-cell carcinoma. Everolimus (Afinitor), an inhibitor of mammalian target of rapamycin (mTOR) demonstrated activity in patients whose cancer had not responded to prior targeted therapy.

Bevacizumab was approved for use in combination with interferon to treat metastatic renal cell carcinoma. Two different trials showed almost a doubling of progression-free survival with the bevacizumab combination compared with interferon alone, although overall survival improved only modestly.

Gynecologic Cancers
Quarterly measurement of CA125 following treatment for ovarian cancer did not reduce the risk of recurrence. The findings from a European study showed that patients did not benefit from early treatment for relapse or recurrence based on CA125 results.

Data from a large multicenter clinical trial demonstrated the efficacy of the human papillomavirus vaccine in older women. The vaccine protected women ages 24 to 45 from HPV infection and both benign and malignant disease of the cervix and genitalia in more than 90% of cases. ASCO specialists said the results show that older women who have not been infected by HPV may derive the same benefits observed in girls and younger women.

Lung Cancer
Maintenance therapy with pemetrexed (Alimta) significantly improved survival in patients with stage IIIB or IV nonsquamous, nonsmall-cell lung cancer (NSCLC). The trial was the first to demonstrate a survival benefit with maintenance chemotherapy, which should now be considered the standard of care for patients with advanced NSCLC, ASCO cancer specialists concluded.

EGFR mutations predicted response to treatment with gefitinib (Iressa) in Asian patients who were nonsmokers or light smokers. Patients with the mutations had a significant slowing of progression when treated with the targeted agent.

M.D. Anderson’s Fisch cited the mutation study as an example of advances that will “likely guide the best choice of treatment.”

Melanoma
A vaccine that boosts the immune system’s response to cancer doubled the response rate of melanoma when added to interleukin-2 (IL-2). Response rates were 9.7% with IL-2 alone and 22.1% with IL-2 and the vaccine.

Central Nervous System Cancers

FDA approval of bevacizumab provided the first new drug for glioblastoma in a decade. Two different trials demonstrated improved progression-free survival and overall survival in patients with advanced glioblastoma treated with bevacizumab.

A monoclonal antibody that stimulates the immune system reduced the risk of recurrence and improved survival in patients with high-risk neuroblastoma. Known as ch14.18, the immunotherapy was associated with a two-year overall survival of 86% compared with 75% with standard therapy and relapse-free survival of 66% compared with 46%.

Hematologic Malignancies
A patient-specific therapeutic vaccine improved disease-free survival in patients with previously untreated follicular lymphoma. Patients randomized to the vaccine had a disease-free survival of 44.2 months compared with 30.6 months for patients who received a control vaccine.

A targeted agent that homes in on an enzyme involved in inflammation and immune response demonstrated activity against several types of blood cancers in a Phase I clinical trial. Fostamatinib, which inhibits the enzyme Syk kinase, achieved measurable responses in 5% of patients with chronic lymphocytic leukemia, 21% of patients with diffuse large-cell lymphoma, 11% of patients with mantle-cell lymphoma, and 10% of patients with follicular lymphoma.

Cancer Prevention and Screening
Two large randomized clinical trials showed that routine screening for prostate cancer with PSA tests had little or no effect on prostate cancer mortality. ASCO cancer specialists said the message from the trials is that routine PSA testing detects a large number of clinically insignificant cancers and can lead to unnecessary treatment.

The University of North Carolina’s Muss said the PSA studies and the trial that evaluated CA125 as a guide to therapy both should have a practice-changing impact on oncology.

The ASCO report also reviews the organization’s major recommendations for the past year, emphasizing ASCO’s support for increased funding for cancer research and removal of regulatory barriers to research, implementation of quality-of-care measures for cancer care, and elimination of barriers to access to high-quality cancer care.

Focusing on policy issues, Roy Jones, MD, of M.D. Anderson, cited a need for insurance coverage that addresses the impact of new technology on the cost of healthcare. He suggested a two-tiered system of coverage comprising a basic insurance plan for “proven cost-effective care” and supplemental policies that “willing purchasers would pay for the privilege of unproven high-tech.”

“Since the current healthcare reform proposals fail to address the major cost driver, they are all unlikely to reduce costs,” said Jones. “On that pessimistic note, we might be able to consider this or similar plans the ‘go round.'”

Note:
1. This article was developed in collaboration with ABC News.
2. Primary source: Journal of Clinical Oncology
3. Source reference: Petrelli N, Winer EP, eds “Clinical cancer advances 2009. Major research advances in cancer treatment prevention, and sceening” J Clin Oncol Epub.

November, 2009|Oral Cancer News|

At our throats

Source: www.forbes.com
Author: Matthew Herper

Oncologist Maura Gillison was looking for patients with tonsil cancer for a clinical study several years ago. The first enlisted was a malpractice lawyer, followed by a doctor, then a scientist. She joked to a colleague that all she needed was a rear admiral. In walked a member of the military brass. All were in their 30s, 40s and 50s.

People in their prime didn’t used to get throat tumors. Head-and-neck cancer, as doctors call it, was a disease of older problem drinkers who also chain-smoked (more men than women). Years of exposure to scotch and Lucky Strikes would damage the DNA of cells lining the throat, leading to cancer.

But Gillison, 44, a professor at Ohio State University, was among the first researchers to make a startling realization: The old cigarettes-and-alcohol form of the disease was being eclipsed by a new form, caused by the same human papilloma virus (HPV) that causes cervical cancer. The tumors grow in the tonsils or in the tissue that remains after tonsillectomy. The only good news is that the prognosis for these patients is better than for the old disease.

Gillison and researchers at the National Cancer Institute estimate that 4,000 people, 75% of them men, develop this new form of throat cancer annually. That’s only a tenth of head-and-neck cases, but it’s half as many people as get cervical cancer in the U.S. More worrisome, Gillison’s work shows HPV tonsil cancer is increasing at a rate of 5% a year, unusual growth for a cancer diagnosis, even though throat infection with the HPV strain that causes it is exceedingly rare. Any spread of the virus could make the number of cases increase dramatically. “I’m very worried,” says Otis Brawley, chief medical officer of the American Cancer Society. Skeptics say the association is not proven, and that too much of the work comes from just Gillison.

Both Gillison and Brawley think a solution may exist: Vaccinate all boys, starting as early as age 9, with Merck’s HPV vaccine, Gardasil, now heavily promoted for cervical cancer. Gardasil, however, is already the source of all sorts of controversy. Antivaccine groups oppose it because of its high costs ($360 for three shots) and alleged side effects; the FDA says the vaccine is safe. GlaxoSmithkline is developing its own HPV vaccine.

Gillison spent three years trying to draw Merck’s attention to HPV tonsil cancer. Finally, she is working with Merck to design a study to see if Gardasil can affect HPV infection in the throat. Merck admits studying the problem is “challenging” but says the potential is big.

Interested in cancer-causing viruses, Gillison started work on the HPV problem in 1996 when she was finishing her Ph.D. and oncology training at Johns Hopkins University. She signed up with a group studying HPV and cervical cancer. But she switched to studying throat cancer patients after finding a few research papers reporting cases in which tumors had the DNA of the HPV virus inside them.

She was shocked to find a substantial number of throat tumors had the HPV type. She also noticed something dramatic when she organized HPV patients by the year they were born. Starting with patients born in 1935, there had been an increase in the number of cases every single year.

Researchers realized that a big change in sexual behavior in the 1950s and 1960s–mainly, that people had more sexual partners–had allowed a virus that had been rare to spread throughout the population. Some researchers say gay men and women seem underrepresented, possibly because they catch the virus elsewhere in the body and develop immunity.

What appears to happen is that one strain of the HPV virus, which is transmitted largely through oral sex, but also by French kissing or even just sharing a water glass, suppresses two anticancer genes.

HPV tonsil cancer is not as lethal as traditional throat cancers, but the treatment is still brutal. Martin Duffy, a 69-year-old Boston economist and consultant who doesn’t smoke and has run 40 Boston marathons, dropped 30 pounds to 120 pounds while being treated with Erbitux and radiation. He was diagnosed with tonsil cancer in February and is slowly recovering.

The death rate in head-and-neck cancer has been dropping, but doctors are still discouraged: It turns out the less threatening virus was responsible for many of those cancers. James Rocco, a head-and-neck surgeon at the Massachusetts Eye & Ear Infirmary, says, “We’re probably doing no better than we were 30 years ago.”

October, 2009|Oral Cancer News|

Erbitux® may improve treatment of squamous cell carcinoma of the esophagus

Source: professional.cancerconsultants.com
Author: staff

Researchers from Germany have reported that Erbitux® (cetuximab) improves response rate, time to disease progression, and overall survival of patients with metastatic squamous cell carcinoma receiving Platinol® (cisplatin) and 5-FU. The details of this study appeared in the October 2009 issue of Annals of Oncology.[1]

Esophageal cancer is relatively common and is very deadly. It 1998 there were approximately 12,300 new cases of esophageal cancer diagnosed in the United States and nearly 12,000 esophageal cancer deaths, making esophageal cancer one of the most deadly of all cancers. Most cancers of the upper two-thirds of the esophagus arise from squamous cells. Cancers of the lower esophagus most often arise from columnar epithelium and are adenocarcinomas. In the recent past, squamous cell cancers made up more than 80% of all esophageal cancers. Over the past two decades, there has been a dramatic increase in the incidence of adenocarcinomas, which now account for one-third to one-half of all esophageal cancers. However, squamous cell carcinoma of the esophagus remains a major problem and is difficult to treat when metastatic. Usual treatment for metastatic squamous cell carcinoma of the esophagus includes a platinum compound and 5-FU.

Erbitux is a chimeric monoclonal antibody that binds to the outer domain of the epidermal growth factor receptor (EGFR). It is currently approved, in combination with radiation therapy, for the treatment of locally or regionally advanced head and neck cancer, or as a single agent in the treatment of advanced, EGFR-expressing head and neck cancer that has failed prior platinum-based therapies. Early studies have suggested activity for Erbitux for treating squamous cell carcinoma of the esophagus.

The current study randomly allocated 62 patients with metastatic squamous cell carcinoma of the esophagus to treatment with Platinol and 5-FU with or without Erbitux. Toxicity of Erbitux included skin rash and diarrhea. The overall response rate of patients receiving Erbitux was 19% compared with 13% for the chemotherapy-alone group. Disease-control rate was 75% for patients receiving Erbitux and 57% for patients receiving chemotherapy alone. The median progression-free survival was 5.9 months for patients receiving Erbitux and 3.6 months for patients receiving chemotherapy alone. Median survival was 9.5 months for patients receiving Erbitux and 5.5 months for patients receiving chemotherapy alone. No KRAS mutations were identified in 37 specimens.

Comments: Erbitux appears to be active for the treatment of squamous cell carcinoma of the esophagus.

Reference:
[1] Lorenzen S, Schuster T, Porschen R, et al. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgeminschaft Internistische Onkologie. Annals of Oncology. 2009; 20:1667-1673.

October, 2009|Oral Cancer News|

Lilly Erbitux cancer drug not worth price, U.S. scientists say

Source: www.bloomberg.com
Author: Lisa Rapaport

Eli Lilly & Co.’s tumor-fighter Erbitux doesn’t prolong lung cancer patients’ lives enough to justify its $80,000 cost, U.S. scientists said in commentary published today.

Erbitux added to other cancer drugs extends survival about 1.2 months more than chemotherapy alone, making the price too high for a “marginal benefit,” commentary in the Journal of the National Cancer Institute said. Erbitux, which Lilly markets with Bristol-Myers Squibb Co., generated $1.3 billion last year as treatment approved for other malignancies.

The high price of some of the newest cancer medicines are coming under scrutiny as part of an effort by lawmakers and health officials to rein in overall medical costs. President Barack Obama has set aside $1.1 billion in the U.S. economic stimulus bill to study the comparative effectiveness of treatments for cancer and other diseases.

“We must avoid the temptation to tell a patient that a new drug is available if there is little evidence that it will work better than established drugs that could be offered at a miniscule fraction of the cost,” wrote the commentators, Tito Fojo with the National Cancer Institute and Christine Grady at the National Institutes of Health.

Lilly, of Indianapolis, and marketing partner Bristol- Myers, of New York, withdrew an application to extend the Erbitux’s use to lung tumors in February after the Food and Drug Administration questioned differences in American and European versions of the treatment.

$10,000 a Month

The authors projected that Erbitux costs $80,000 based on a typical course of treatment for lung tumors, 18 weeks. If all 550,000 U.S. patients who die of cancer each year took 12 months of Erbitux, the total cost would be $440 billion, 100 times the annual budget of the National Cancer Institute, the authors said.

Bristol-Myers estimated Erbitux’s cost to be lower, at about $10,000 a month, according to company spokesman Brian Henry. The drug is approved to treat head, neck and colon cancer. A Lilly spokeswoman referred questions to Bristol-Myers.

“Erbitux isn’t indicated for all cancer patients, nor would all cancer patients for which Erbitux is indicated necessarily receive the medicine for one year,” Henry said in an e-mailed statement.

Lilly gained Erbitux in its $6.5 billion purchase of ImClone Systems Inc. last year. German drugmaker Merck KGaA markets Erbitux outside the U.S.

Cancer medicines are the best-selling and fastest-growing group of drugs in the U.S., and sales will surge 12 to 15 percent each year to top $75 billion by 2012, according to IMS Health Inc., a pharmaceutical industry research company in Norwalk, Connecticut.

About 220,000 people will be diagnosed with lung cancer in the U.S. this year, and 160,000 will die, according to the National Cancer Institute.

September, 2009|Oral Cancer News|

Initial COIN study results presented at European Oncology Congress

Source: Drugs.com
Author: Staff

• Results inconsistent with data from all Erbitux pivotal studies
• Further analyses planned by the Medical Research Council that conducted the independent COIN study

Berlin/Darmstadt, Germany, September 23, 2009 – The Medical Research Council (MRC), a UK-based, publicly-funded organization dedicated to improving human health, today presented the initial results of the independent Phase III COINa study, which did not meet its primary endpoint of overall survival (OS).1 These findings were presented today at the joint 15th Congress of the European Cancer Organisation (ECCO) and 34th Congress of the European Society for Medical Oncology (ESMO) in Berlin, Germany.

The COIN study was designed to evaluate whether the addition of Erbitux® (cetuximab) to one of two oxaliplatin-based chemotherapy regimens significantly improved outcomes in previously untreated metastatic colorectal cancer (mCRC) patients with KRAS wild-type tumors. The median OS was not statistically significant at 17.0 months in the Erbitux treatment arm compared to 17.9 months for the chemotherapy-alone group (hazard ratio [HR] 1.038; p=0.68).1
“Imbalances in the chemotherapy administered between the different study arms were reported previously in the interim safety analysis,” explained Dr. Wolfgang Wein, Executive Vice President, Oncology, Merck Serono, a division of Merck KGaA, Darmstadt, Germany. “Further analysis of the dose intensity and 2nd-line treatment, and other factors, such as the advanced disease of patients in the study, are ongoing to determine why the COIN results are not aligned with existing evidence from the other randomized, 1st-line studies, including the significant increase in overall survival achieved with the CRYSTAL study.”
Results from the pivotal Phase III CRYSTALb trial also presented earlier today demonstrated that the addition of Erbitux to the standard 1st-line FOLFIRI chemotherapy regimen significantly improved OS in patients with KRAS wild-type tumors (23.5 vs. 20.0 months, HR 0.796, p=0.0094).2 In addition, results from the Phase II OPUSc study, which investigated the benefit of adding Erbitux to the FOLFOX regimen in KRAS wild-type patients, demonstrated:

• Significant improvement in progression-free survival (8.3 vs. 7.2 months, HR 0.567, p=0.0064)

• Significant improvement of response rate (57,3% vs. 34,0%, p=0.0027)

• OS was 22.8 vs. 18.5 months (HR 0.855, p=0.3854).3

a COIN: A Phase III trial comparing either COntinuous chemotherapy plus cetuximab or INtermittent chemotherapy with standard continuous palliative combination chemotherapy with oxaliplatin and a fluoropyrimidine in first line treatment of metastatic colorectal cancer
b CRYSTAL: Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer
c OPUS: OxaliPlatin and cetUximab in firSt-line treatment of mCRC

References
1. Maughan TS, et al. ECCO/ESMO Congress 2009. Abstract No: 6LBA. Updated information presented at meeting.
2. Van Cutsem E, et al. ECCO/ESMO Congress 2009. Abstract No: 6077. Updated information presented at meeting.
3. Bokemeyer C, et al. ECCO/ESMO Congress 2009. Abstract No: 6079. Updated information presented at meeting.

For more information on Erbitux in colorectal, head & neck and non-small cell lungcancer, please visit: www.globalcancernews.com.

About Erbitux
Erbitux® is a first-in-class and highly active IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR). As a monoclonal antibody, the mode of action of Erbitux is distinct from standard non-selective chemotherapy treatments in that it specifically targets and binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal-transduction pathway, which results in reducing both the invasion of normal tissues by tumor cells and the spread of tumors to new sites. It is also believed to inhibit the ability of tumor cells to repair the damage caused by chemotherapy and radiotherapy and to inhibit the formation of new blood vessels inside tumors, which appears to lead to an overall suppression of tumor growth.

The most commonly reported side effect with Erbitux is an acne-like skin rash that seems to be correlated with a good response to therapy. In approximately 5% of patients, hypersensitivity reactions may occur during treatment with Erbitux; about half of these reactions are severe.

Erbitux has already obtained market authorization in 77 countries. It has been approved for the treatment of colorectal cancer in 77 countries and for the treatment of squamous cell carcinoma of the head and neck (SCCHN) in 72 countries:

• December 2003 (Switzerland), February 2004 (USA), June 2004 (EU) and followed by other countries: for use in combination with irinotecan in patients with EGFR-expressing mCRC (metastatic colorectal cancer) who have failed prior irinotecan therapy. In addition, Erbitux is also approved for single-agent use in further countries.
• April 2006 (EU) and followed by other countries: for use in combination with radiotherapy for the treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). In further countries, Erbitux is also approved as monotherapy in patients with recurrent and/or metastatic SCCHN who failed prior chemotherapy.
• July 2008 (EU): license was updated for the treatment of patients with epidermal growth factor receptor (EGFR) expressing, KRAS wild-type mCRC in combination with chemotherapy and as a single agent in patients who have failed oxaliplatin-and irinotecan-based therapy and who are intolerant to irinotecan.
• July 2008 (Japan): for use in combination with irinotecan in patients with EGFR-expressing mCRC who have failed prior irinotecan therapy
• In November 2008 (EU): license was updated for the use in combination with platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN

Merck licensed the right to market Erbitux outside the US and Canada from ImClone Systems, a wholly-owned subsidiary of Eli Lilly and Company, in 1998. In Japan, ImClone Systems, Bristol-Myers Squibb Company and Merck jointly develop and commercialize Erbitux. Merck has an ongoing commitment to the advancement of oncology treatment and is currently investigating novel therapies in highly targeted areas, such as the use of Erbitux in colorectal cancer, squamous cell carcinoma of the head and neck and non-small cell lung cancer. Merck has also acquired the rights for the cancer treatment UFT® (tegafur-uracil) – an oral chemotherapy administered with folinic acid (FA) for the first-line treatment of metastatic colorectal cancer.

Merck is also investigating among other cancer treatments the use of Stimuvax® (formerly referred to as BLP25 Liposome Vaccine) in the treatment of non-small cell lung cancer. The vaccine was granted fast-track status in September 2004 by the FDA. Merck obtained the exclusive worldwide licensing rights from Oncothyreon Inc., Seattle, Washington, USA.
In addition, Merck is developing cilengitide, which is the first in a new class of investigational anti-cancer therapies called integrin inhibitors to reach Phase III of development; it is currently being investigated for the treatment of glioblastoma, SCCHN and NSCLC. Integrin inhibitors are thought to work by targeting the tumor and its vasculature.

Merck is a global pharmaceutical and chemical company with total revenues of € 7.6 billion in 2008, a history that began in 1668, and a future shaped by approximately 33,000 employees in 60 countries. Its success is characterized by innovations from entrepreneurial employees. Merck’s operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.

September, 2009|Oral Cancer News|

U.S. scientists say Lilly Erbitux cancer drug not worth price

Source: Bloomberg
Author: Lisa Rapaport


Eli Lilly & Co.’s tumor-fighter Erbitux doesn’t prolong lung cancer patients’ lives enough to justify its $80,000 cost, U.S. scientists said in commentary published today.

Erbitux added to other cancer drugs extends survival about 1.2 months more than chemotherapy alone, making the price too high for a “marginal benefit,” commentary in the Journal of the National Cancer Institute said. Erbitux, which Lilly markets with Bristol-Myers Squibb Co., generated $1.3 billion last year as treatment approved for other malignancies.

The high price of some of the newest cancer medicines are coming under scrutiny as part of an effort by lawmakers and health officials to rein in overall medical costs. President Barack Obama has set aside $1.1 billion in the U.S. economic stimulus bill to study the comparative effectiveness of treatments for cancer and other diseases.

“We must avoid the temptation to tell a patient that a new drug is available if there is little evidence that it will work better than established drugs that could be offered at a miniscule fraction of the cost,” wrote the commentators, Tito Fojo with the National Cancer Institute and Christine Grady at the National Institutes of Health.

Lilly, of Indianapolis, and marketing partner Bristol- Myers, of New York, withdrew an application to extend the Erbitux’s use to lung tumors in February after the Food and Drug Administration questioned differences in American and European versions of the treatment.

$10,000 a Month

The authors projected that Erbitux costs $80,000 based on a typical course of treatment for lung tumors, 18 weeks. If all 550,000 U.S. patients who die of cancer each year took 12 months of Erbitux, the total cost would be $440 billion, 100 times the annual budget of the National Cancer Institute, the authors said.

Bristol-Myers estimated Erbitux’s cost to be lower, at about $10,000 a month, according to company spokesman Brian Henry. The drug is approved to treat head, neck and colon cancer. A Lilly spokeswoman referred questions to Bristol-Myers.

“Erbitux isn’t indicated for all cancer patients, nor would all cancer patients for which Erbitux is indicated necessarily receive the medicine for one year,” Henry said in an e-mailed statement.

Lilly gained Erbitux in its $6.5 billion purchase of ImClone Systems Inc. last year. German drugmaker Merck KGaA markets Erbitux outside the U.S.

Cancer medicines are the best-selling and fastest-growing group of drugs in the U.S., and sales will surge 12 to 15 percent each year to top $75 billion by 2012, according to IMS Health Inc., a pharmaceutical industry research company in Norwalk, Connecticut.

About 220,000 people will be diagnosed with lung cancer in the U.S. this year, and 160,000 will die, according to the National Cancer Institute.

To contact the reporter on this story: Lisa Rapaport in New York atLrapaport1@bloomberg.net

June, 2009|Oral Cancer News|

Use of Erbitux in head and neck cancer rejected by NICE

Source: Pharmafocus.com

Author: Staff

Erbitux has failed to win NICE approval for the treatment of head and neck cancer, due to doubts over its cost and clinical effectiveness compared to existing treatments.

It was rejected under NICE’s new scheme to make more end-of-life drugs available by extending the threshold at which they are considered cost-effective, making it an extra heavy blow for manufacturer Merck Serono.

Chief executive Andrew Dillon defended NICE’s decision, saying the alternative of approving the medicine for the health service was unviable.

He added: “This would mean the NHS making significant funds available for a very expensive treatment which may or may not benefit individual patients. Those funds would not then be available for treating other conditions with greater and more certain benefits for other patients.”

Erbitux is a monoclonal antibody and one of a new class of cancer drugs which target genetic mutations that allow cancer cells to multiply, and are designed to bypass many of the unpleasant side-effects associated with traditional chemotherapy.

Licensed also in colorectal cancer, in 2008 the drug made global sales of nearly $1.6 million in 2008, and is expected to reach sales of $3.4 million by 2014.

In the latest appraisal, Erbitux was rejected as a treatment of recurrent and/or metastatic squamous cell cancer of the head and neck and NICE recommended against its use in combination with platinum-based chemotherapy in patients with this cancer.

The appraisal committee were uncertain over the clinical effectiveness of the drug and the cost of the treatment when compared to those currently available.

In the cost-effectiveness analysis submitted by Merck Serono, treatment with Erbitux and chemotherapy compared with chemotherapy alone would result in the cost of an extra QALY – the equivalent price of providing one additional year of healthy life – at £121,367.

With this extra cost the predicted gain in overall survival of patient prescribed Erbitux would only be just over two months.

The appraisal board also took into account the supplementary advice provided by NICE when appraising treatments at the end of life, noting that Erbitux was used for a small population with a short life-expectancy, and therefore the threshold at which the drug is considered cost-effective should be extended.

But it concluded the treatment still did not offer sufficiently greater benefits to these patients compared to existing treatments.

The decision is a blow for Merck Serono, which has come to expect much from the ascendant oncology drug, now ranked fifth in the world’s top cancer treatments.

The company received more positive news from NICE recently, when it approved Erbitux in another indication, making it a first-line therapy for many patients with a certain type of metastatic colorectal cancer.

June, 2009|Oral Cancer News|

Monoclonal Antibody Drugs for Cancer Treatment

Source: www.newswise.com
Author: staff

The strategy of using monoclonal antibodies for cancer treatment was first described in the late 1970s with the promise that they could be developed into therapies that were highly specific to cancer cells, killing them with few or no side effects. For several types of cancer, monoclonal antibodies have already offered this advantage to patients. For other cancer types, they have provided an additional therapeutic weapon, but with smaller benefits and sometimes new side effects.

“The first efforts for monoclonal antibody cancer therapy were to find antibodies that would home in on tumors and bind to proteins on the surface of cancer cells,” explained physician-scientist David A. Scheinberg. “We looked for unique proteins that were specific only to cancer cells. The idea was that the antibody would be used to stimulate an immune response in the body, which would kill the cancer cell.” Dr. Scheinberg, who is Chair of Memorial Sloan-Kettering’s Experimental Therapeutics Center and the Molecular Pharmacology and Chemistry Program within the Sloan-Kettering Institute, developed an antibody called M195, which targets a protein on leukemia cells, when working as a research fellow in collaboration with Memorial Sloan-Kettering immunologist Lloyd Old in the 1980s.

This approach further evolved when researchers realized they could use the antibody as a carrier to deliver a radioactive isotope or a toxic drug directly to the cancer cell, where it would kill the cell while sparing nearby healthy tissue.

Antibodies are proteins that help the immune system to identify foreign substances by binding to them and marking them as foreign. Monoclonal antibodies are manufactured using a type of cell called a hybridoma. The hybridoma — which is engineered in the laboratory by fusing an antibody-producing immune cell called a B cell to a tumor cell — multiplies to produce a continuous supply of a specific antibody. Early monoclonal antibodies were made exclusively from mouse cells, but because the immune system can recognize these antibodies as foreign, leading to unwanted reactions, most monoclonal antibodies used today are either chimeric, consisting of both mouse and human parts, or fully human.

Improving Survival for Lymphoma
The first monoclonal antibody approved for cancer was rituximab (Rituxan®) in 1997. It was initially developed by Ronald Levy at the Stanford School of Medicine to treat follicular lymphoma, the most common type of indolent (slow-growing) non-Hodgkin’s lymphoma. “When rituximab was developed, everyone working in the field thought it was going to be a marginal drug that would benefit a small number of patients with relapsed and refractory disease,” remembered Andrew D. Zelenetz, Chief of Memorial Sloan-Kettering’s Lymphoma Service. “But it turned out we were all wrong. For patients with follicular lymphoma, a combination of rituximab with chemotherapy has resulted in improved disease control and prolonged survival. In patients with diffuse large B cell lymphoma, the most common lymphoma subtype worldwide, the addition of rituximab to the standard chemotherapy protocol known as CHOP increased the cure rate by about 15 percent.”

Rituximab, which binds to the protein CD20 on the surface of B cells, has three different mechanisms of action. Its primary way of killing cancer cells is by eliciting an immune response, drawing what are known as effector cells (various types of killer white blood cells) to the tumor and activating them. This process is called antibody-dependent cell-mediated cytotoxicity (ADCC). Another mechanism is directly causing the cells to undergo apoptosis (programmed cell death). The third mechanism is by activation of what are called complement proteins. These proteins form a membrane-attack complex and poke holes in the membranes of cells, killing them.

Because CD20 is present on the surface of normal B cells as well as leukemia cells, normal B cells are killed as well. “We make 10 million B cells a day, and most of them die anyway,” Dr. Zelenetz said. “So when we target B cells and knock them out, they are easily replaced. It’s possible that long-term use of rituximab could lead to an increased risk of some types of infections, but it’s something we really haven’t seen as a frequent problem.”

Two other drugs for lymphoma make use of antibodies as carriers for radioactive isotopes. Ibritumomab tiuxetan (Zevalin®), developed by a small pharmaceutical company, contains an antibody similar to rituximab linked to yttrium-90, a radioisotope that emits a cell-blasting beta particle. Tositumomab (Bexxar®), developed by Mark Kaminski and Richard Wahl, then at the University of Michigan, is an antibody that carries the beta-emitting isotope iodine-131. Both antibodies also target CD20.

Less Toxic Treatments for Leukemia
Another tactic for using antibodies as delivery devices is attaching them to a cytotoxic agent, such as a chemotherapy drug. Gemtuzumab (Mylotarg®), a drug that is used to treat acute myelogenous leukemia (AML), consists of an antibody connected to calicheamicin, a highly toxic antibiotic. Gemtuzumab, developed at the Fred Hutchinson Cancer Research Center, targets CD33, a protein found on the surface of leukemia cells.

“The average age for AML patients is 68,” said Joseph G. Jurcic, Acting Chief of Memorial Sloan-Kettering’s Leukemia Service. “Most of these patients cannot tolerate intensive treatments such as bone marrow transplantation, and their prognosis is usually poor. For them, a drug like gemtuzumab allows them to avoid the side effects of standard chemotherapy given systemically throughout the entire body.” Gemtuzumab allows about 15 percent of patients to achieve a complete remission when it is given to patients who have had only one relapse.

Lintuzumab is another monoclonal antibody that targets CD33. It is the humanized version of M195, the antibody initially developed by Dr. Scheinberg. It is currently being evaluated in a number of late-stage clinical trials for AML as well as for myelodysplastic syndromes, a group of diseases that frequently lead to AML and other types of leukemia.

Drs. Scheinberg and Jurcic are also taking their research with lintuzumab to the next level, using it to deliver a next-generation cancer treatment, dubbed a nanogenerator, to cancer cells. The nanogenerator consists of a single radioactive atom contained inside a molecular cage. The atom, actinium-225, decays by giving off high-energy alpha particles, which kill cancer cells. When actinium decays, it produces a series of daughter atoms, each of which gives off its own alpha particle, increasing the chances that the cancer cell will be destroyed. The technology was first demonstrated by Dr. Scheinberg in mice in 2001, and Dr. Jurcic is currently testing the drug in leukemia patients. Further studies starting early next year at several centers nationwide, including Memorial Sloan-Kettering, will combine the drug with standard chemotherapy.

Alemtuzumab (Campath®) is an antibody drug approved for another type of leukemia, called B cell chronic lymphocytic leukemia (CLL). Alemtuzumab, based on an antibody developed by British immunologist Herman Waldmann, targets the CD52 protein, which is found on the surface of these tumor cells as well as T cells. Because it destroys both B and T cells, alemtuzumab has activity in a variety of lymphoid malignancies, although it is specifically approved for treatment of CLL.

Experimental Treatments for Neuroblastoma
Another monoclonal antibody developed at Memorial Sloan-Kettering is called 3F8. 3F8 is used to treat neuroblastoma, a rare pediatric cancer of the nervous system that affects about 750 children in the United States every year. It has been used at the Center for 20 years to treat metastatic neuroblastoma. “Two decades ago the advanced form of the disease had almost no long-term survivors,” according to Nai-Kong V. Cheung, an Memorial Sloan-Kettering pediatric oncologist who developed the antibody. “But since the antibody treatment has become part of the standard of care at Memorial Hospital, long-term survival is about 60 percent.”

The antibody is given after induction chemotherapy (initial chemotherapy given to induce a remission), in combination with a drug called GM-CSF (granulocyte/macrophage colony-stimulating factor), which boosts the production of white blood cells. Most neuroblastoma patients also undergo surgery to remove their primary tumor and radiation therapy. The main side effect of 3F8 is intense pain at the time the antibody is given, but the pain is short-lived and does not have long-term effects. Currently 3F8 is available only to patients at Memorial Sloan-Kettering, but it has recently been licensed to a company that will begin evaluating it in randomized studies at other centers around the country.

3F8 targets a sugar lipid called GD2, which is abundant on the surface of neuroblastoma cells. It kills neuroblastoma cells using the same three mechanisms that rituximab uses to kill B cells: by inducing cell death directly, by activating complement proteins, and through ADCC. “With ADCC, the antibody is like a middleman,” Dr. Cheung explained. “It brings the tumor cells and the white blood cells together. The white blood cells act as professional killers, destroying the tumor.”

Memorial Sloan-Kettering investigators are looking at new approaches to make 3F8 more effective for the 40 percent of patients who don’t respond. “We believe patients who don’t respond have a different genetic makeup from those who do,” Dr. Cheung said. One current line of research is giving patients donor white blood cells (a type called natural killer cells) in combination with 3F8, “to try to bypass that genetic disadvantage in certain patients,” he explained.

For patients whose neuroblastoma spreads to the brain, one of the sites of metastasis when the disease relapses, 3F8 and another antibody called 8H9 can also be armed with radioactive iodine. Because antibodies are large molecules that are unable to cross the blood-brain barrier, the treatment is injected directly into the cerebrospinal fluid. This experimental treatment has been given to only a handful of pediatric patients so far — some with brain metastases and some with primary brain tumors — but preliminary results look very promising, and about three-quarters of neuroblastoma patients who received the treatment are doing well up to five years later.

“Brain metastases are not a trivial issue in cancer,” Dr. Cheung said. “More than 20 percent of metastatic cancers, including adult cancers such as breast cancer, have the tendency to spread to the brain. We think this form of ‘liquid radiation,’ which delivers radioisotopes directly to the tumor, can minimize side effects seen with external-beam radiation and can eventually be developed for treating a range of pediatric and adult cancers that attack the brain.”

Blocking the Growth of Solid Tumors
One of the most well-known monoclonal antibody drugs is cetuximab (Erbitux®). First known as C225 and developed at the University of California, San Diego, by former Chair of Memorial Sloan-Kettering’s Department of Medicine John Mendelsohn, before he arrived at the Center, the antibody prevents activation of a growth-signaling pathway that is found in many solid tumors, including colorectal cancer, lung cancer, and cancers of the head and neck.

Cetuximab binds to epidermal growth factor receptor (EGFR), a protein that is present on the surface of both tumor cells and normal cells, especially skin cells. When cetuximab binds, it may act by preventing EGFR from activating signaling molecules that would normally tell the cell to grow and divide. In cancer cells, this can block growth and shrink the tumor. However, when the antibody binds to skin cells, it can cause severe rashes.

Cetuximab is used in combination with chemotherapy to treat colorectal and head and neck cancers, and studies show that it improves overall survival by about six weeks in colorectal cancer and three months in head and neck cancers.

Panitumumab (Vectibix®), developed by Amgen, is another monoclonal antibody that targets EGFR and is approved for the treatment of colorectal cancer. Panitumumab is used as a single agent, and although it improves progression-free survival (the time it takes for the cancer to get worse), it has not been shown to improve overall survival.

Another strategy for treating solid tumors is by inhibiting angiogenesis, the flow of blood supply to tumors that allows them to grow. The monoclonal antibody bevacizumab (Avastin®) works by blocking a protein called vascular endothelial growth factor (VEGF). When the VEGF protein is blocked, existing blood vessels on tumors are destroyed and the growth of additional blood vessels is prevented. Bevacizumab, developed by Genentech scientist Napoleone Ferrara, is also is used in combination with chemotherapy and is approved for the treatment of colorectal, lung, and breast cancers. However, for most patients with advanced disease the improvement in survival times is small.

“Overall, the majority of monoclonal antibodies developed for solid tumors have been relatively disappointing compared to our early hopes and expectations,” said Memorial Sloan-Kettering medical oncologist Leonard Saltz, who led some of the large trials for cetuximab. “They are useful, but our original hope was that these drugs would be able to replace chemotherapy, rather than be combined with chemotherapy. Patients still have the side effects of the original chemotherapy treatment, and in some cases extra side effects from the antibodies. In addition, these drugs are very expensive, and most of them have only modest benefits.”

Targeting Signaling Pathways in Breast Cancer
A solid tumor for which monoclonal antibodies have shown a more meaningful benefit, at least for a subset of patients, is breast cancer. About 20 percent of breast cancers have high levels of a protein called human epidermal growth factor receptor-2 (HER2). Tumor growth in HER2-positive tumors is caused by signaling from the excess of HER2 protein: HER2 binds to other proteins in the HER family and sends signals telling cancer cells to grow and to not undergo programmed cell death.

“HER2 is a good target for anticancer agents because HER2-positive cancers tend to be more aggressive,” said Clifford A. Hudis, Chief of Memorial Sloan-Kettering’s Breast Cancer Medicine Service. “When these tumors come back after surgery, they usually come back early.”

Trastuzumab (Herceptin®) was developed to stop HER2 signaling. “We still don’t know exactly how trastuzumab works,” Dr. Hudis explained. “In part, it may be making changes to the receptor on the cell’s surface. It may be turning on an immune reaction via ADCC. It may also activate a process called endocytosis, where it binds to the receptor and then the whole complex is swallowed up by the cell, and it may inhibit a protein called p95.”

Trastuzumab, jointly developed by Genentech and Dennis Slamon of the University of California, Los Angeles, usually is given in combination with chemotherapy, and for women with late-stage disease it has been shown to improve average survival about 25 percent compared with chemotherapy alone. For women with earlier-stage disease, it can be given as an adjuvant (additional) treatment after surgery. For those patients, the drug can provide a substantial benefit, killing microscopic metastatic disease that is not clinically apparent, improving the rate of cure by 50 percent compared with chemotherapy alone.

One problem with trastuzumab, as with other targeted therapies, is that many patients eventually develop resistance to the treatment. An approved drug for such patients is the small-molecule drug lapatinib (Tykerb®), which blocks HER2 signaling via a different mechanism. In addition, there are several experimental therapies in clinical trials at the Center that help get around that resistance. One is a drug called T-DM1, which consists of trastuzumab linked to a cytotoxic chemotherapy agent. Another monoclonal antibody in studies around the world is pertuzumab, which binds to the HER2 receptor in a different location than trastuzumab does. There is also a family of new small-molecule drugs, called heat shock protein 90 inhibitors, developed in part in the laboratory of Memorial Sloan-Kettering investigator Neal Rosen, that can help amplify the trastuzumab effect even in patients for whom the antibody seems to have stopped working.

For patients with HER2-normal (meaning not HER2-positive) breast cancer who have experienced relapse or recurrence after other treatments, bevacizumab can be given in combination with chemotherapy drugs. “Bevacizumab is currently being evaluated as an adjuvant treatment for patients with an earlier stage of disease,” Dr. Hudis said, “but it is too early to know if patients will benefit from it.”

Researchers agree that while the use of monoclonal antibodies has yet to be fully optimized and has not reached its full potential, the antibodies can still clearly benefit a large number of patients and teach investigators more about the biology of cancer.

April, 2009|Oral Cancer News|

Update FDA seeks more Erbitux data on head and neck cancer

Source: www.reuters.com
Author: Ransdell Pierson

U.S. regulators have declined to approve use of Erbitux as a first-line treatment for head and neck cancer until a new U.S. animal study is conducted showing how the medicine is absorbed by the body, drugmakers Eli Lilly and Bristol-Myers Squibb said on Monday.

Lilly and Bristol-Myers had asked the U.S. Food and Drug Administration to approve first-line use of Erbitux based on favorable head and neck cancer data from overseas studies conducted by German drugmaker Merck KGaA.

Merck sells Erbitux outside the United States. Lilly separately makes Erbitux and sells it in the United States in partnership with Bristol-Myers.

The FDA wants an additional study to ascertain that both batches of Erbitux have the same pharmacokinetic profile, meaning the drug is absorbed in the bloodstream in similar fashion and amounts, said Lilly spokeswoman Judy Kay Moore.

“They want an additional preclinical trial to study comparability” of Erbitux batches, Moore said.

Lilly and Bristol-Myers recently withdrew their U.S. application to market Erbitux for advanced non-small cell lung cancer because of the same need to confirm comparability of batches made in different plants.

“Essentially we will do one animal study and that will answer the pharmacokinetic comparability questions related to first-line treatment for both head and neck and lung cancer,” Moore said.

Lilly hopes to refile the lung cancer marketing application in the second half of 2009, Moore said.

She said the company does not need to refile its application for first-line treatment of head and neck cancer because it is a “standing application.” Moore declined to speculate when the FDA would receive the requested new data and render its decision on use of Erbitux for that condition.

Erbitux is already approved in the United States to treat advanced head and neck cancer, in combination with radiation, and as a stand-alone treatment for patients with recurrent or metastatic head and neck cancer that have failed to benefit from standard treatment. Its biggest use, however, is as a treatment for colorectal cancer.

March, 2009|Oral Cancer News|