erbitux

FDA Approves Cetuximab for Late-Stage Head and Neck Cancer

Source: The Oncology Report

The Food and Drug Administration on Nov. 7 approved cetuximab as an initial treatment of late-stage head and neck cancer in combination with chemotherapy.

Cetuximab, marketed as Erbitux by Bristol-Myers Squibb, is an epidermal growth factor receptor (EGFR) antagonist, administered as an intravenous infusion. Previously, it was approved in combination with radiation therapy for the initial treatment of locally or regionally advanced squamous cell carcinoma. It was also approved for use alone in patients with recurrent locoregional disease or metastatic disease whose disease has progressed following platinum-based chemotherapy.

The newly approved indication is for the treatment of these recurrent or metastatic patients as an initial therapy in combination with platinum-based therapy with 5-fluorouracil (5-FU), a BMS spokesperson said. (At press time, the company had not yet issued a statement on the approval.)

Erbitux was initially approved in 2004 to treat EGFR-positive late-stage colon cancer after patients stopped responding to chemotherapy and was approved in 2006 for the treatment of head and neck cancer. The newly approved indication is for “recurrent locoregional disease or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based therapy with 5-FU,” according to the revised label, posted on the FDA Web site.

The two previously approved indications for head and neck cancer were for “locally or regionally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy,” and for “recurrent or metastatic squamous cell carcinoma of the head and neck progressing after platinum-based therapy.

“Erbitux’s ability to extend the lives of patients with head and neck cancers is an important tool for oncologists who often rely on a multitreatment approach for patients,” Dr. Richard Pazdur, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research said in the statement. “Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible,” he added.

The approval was based on a multicenter study of 442 patients who had metastatic or recurrent head and neck cancer, which was inoperable or widespread, and of those who had not been treated with chemotherapy. The study was conducted outside of the United States and used a version of cetuximab that is not approved in the United States, the statement said.

The median overall survival among patients who were treated with cetuximab and chemotherapy (cisplatin or carboplatin and 5-fluorouracil) combination was 10.1 months, compared with 7.4 months among those who received chemotherapy alone cisplatin or carboplatin and 5-fluorouracil, the FDA statement said.

The most common adverse events reported by patients in the cetuximab plus chemotherapy arm were rash; pruritus; nail changes; headache; diarrhea; and respiratory, skin, and mouth infections, according to the FDA.

Other adverse effects that have been associated with cetuximab include low serum levels of magnesium, potassium, and calcium; and potentially fatal infusion reactions and myocardial infarctions. Sun exposure should be limited during treatment.

Cetuximab available in the United States provides about 22% greater exposure than the European Union–approved cetuximab that was used in this study, but this pharmacokinetic data along with the results of this study “and other clinical trial data establish the efficacy of Erbitux at the recommended dose,” according to the revised prescribing information posted on the FDA Web site.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2011|Oral Cancer News|

US FDA approval for expanded use of Erbitux

Source: www.pharmabiz.com
Author: staff

The US Food and Drug Administration (FDA) has approved Erbitux (cetuximab), in combination with platinum-based chemotherapy with 5-fluorouracil (CT), for the first-line treatment of recurrent locoregional or metastatic squamous cell carcinoma of the head and neck (SCCHN).

The approval, which is based on data from the landmark EXTREME (ErbituX in first-line Treatment of REcurrent or MEtastatic head & neck cancer) trial, makes Erbitux plus CT the first treatment regimen approved in 30 years with extended overall survival in patients with recurrent locoregional or metastatic SCCHN.

Erbitux (cetuximab) is a monoclonal antibody (IgG1 Mab) designed to inhibit the function of a molecular structure expressed on the surface of normal and tumour cells called the epidermal growth factor receptor (EGFR, HER1, c-ErbB-1). In vitro assays and in vivo animal studies have shown that binding of ERBITU Erbitux GFR blocks phosphorylation and activation of receptor-associated kinases, resulting in induction of apoptosis (cell death), inhibition of cell growth, and decreased matrix metalloproteinase and vascular endothelial growth factor production. In vitro, Erbitux can mediate antibody-dependent cellular cytotoxicity (ADCC) against certain human tumor types. In vitro assays and in vivo animal studies have shown that Erbitux inhibits the growth and survival of tumour cells that express the EGFR. No anti-tumour effects of Erbitux were observed in human tumour xenografts lacking EGFR expression.

EXTREME, which was previously published in the New England Journal of Medicine, was a phase III open label, randomized, multi-centre, controlled trial. This study was conducted outside the US by Merck KGaA, Darmstadt, Germany, and used European Union (EU)-approved cetuximab. Erbitux provides approximately 22% higher exposure relative to the EU-approved cetuximab used in the EXTREME trial; these pharmacokinetic data, together with the results of the EXTREME trial and other clinical trial data establish the efficacy of Erbitux at the recommended dose. EXTREME showed that cetuximab plus CT in the first-line treatment of recurrent locoregional or metastatic SCCHN resulted in superior efficacy across clinically meaningful endpoints, including overall survival, progression-free survival, and objective response rate compared to CT. Cetuximab plus CT significantly extended patients’ median overall survival by 36% compared to patients who received CT alone (10.1 months vs. 7.4 months, respectively) [HR: 0.80; 95% CI: 0.64-0.98; p=0.034]. Cetuximab plus CT also significantly increased median progression-free survival by 67% (5.5 vs. 3.3 months, respectively) [HR: 0.57; 95% CI: 0.46-0.72; p<0.0001] compared to CT alone. A significant improvement in objective response rate was also demonstrated (36% vs. 20%, odds ratio, 2.33 [95% CI: 1.50-3.60]; p=0.0001).

Serious infusion reactions occurred with the administration of Erbitux in approximately 3 per cent of patients in clinical trials, with fatal outcome reported in less than 1 in 1000. Healthcare providers should immediately interrupt and permanently discontinue Erbitux infusion for serious infusion reactions. Cardiopulmonary arrest and/or sudden death occurred in 2 per cent of patients with squamous cell carcinoma of the head and neck treated in a clinical trial with Erbitux and radiation therapy and in 3 per cent of patients with squamous cell carcinoma of the head and neck treated with EU-approved cetuximab in combination with platinum-based therapy with 5-fluorouracil (5-FU) in the EXTREME trial. Healthcare providers should closely monitor serum electrolytes, including serum magnesium, potassium, and calcium, during and after Erbitux administration.

Bristol-Myers Squibb and Lilly are committed to supporting patient access to ERBITUX and have put in place a number of programmes to help patients and providers. Destination Access, which is a Reimbursement Support Program, helps patient access by providing benefits investigation support, prior authorization assistance, appeals assistance and patient assistance.

November, 2011|Oral Cancer News|

FDA Approves Cetuximab for Metastatic Head and Neck Cancer

Source: MedScape News Today

The US Food and Drug Administration (FDA) has approved cetuximab (Erbitux, Bristol-Myers Squibb ) for use in combination with chemotherapy for the treatment of metastatic head and neck cancer.

Data show that when combined with cisplatin-based chemotherapy, cetuximab improved overall survival, compared with chemotherapy alone. According to the researchers, this is the first time in 3 decades — since cisplatin was first used in head and neck cancer — that any regimen has improved on its success. The improved survival that was seen after cetuximab was added to the regimen (at a median of 2.7 months) is “therefore notable.”

Cetuximab was approved in the United States in 2004 for the treatment of epidermal growth-factor receptor–positive late-stage colon cancer in patients who no longer responded to chemotherapy. In 2006, it was approved for use in combination with radiation therapy for the treatment of locally or regionally advanced squamous cell carcinoma of the head and neck. This latest approval expands on that to cover metastatic head and neck cancer.

The ability of cetuximab “to extend the lives of patients with head and neck cancer is an important tool for oncologists, who often rely on a multitreatment approach for patients,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, in a statement.” Given the aggressive nature of head and neck cancers that cannot be treated with surgery and radiation, it is important that patients have as many treatment options available as possible.”

EXTREME Trial

The safety and effectiveness of cetuximab for this indication is based on the results of a multicenter clinical study — the Erbitux in First-Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) trial. The results of this study were first reported at the 2007 meeting of the American Society of Clinical Oncology. At the time, experts in the field predicted that they would change clinical practice. The results were subsequently published in 2008 (N Engl J Med. 2008;359:1116-1127).

Cetuximab was granted approval by the European Commission in November 2008 for the treatment of first-line recurrent and/or metastatic head and neck cancer on the basis of the EXTREME study.

The trial involved 442 patients with untreated recurrent or metastatic squamous cell carcinoma of the head and neck; approximately 60% of the cohort had not received any previous chemotherapy. All patients received chemotherapy with a platinum agent (cisplatin or carboplatin, chosen by the investigator) plus infusional 5-fluorouracil. Half of the patients were randomized to also receive cetuximab.

On average, patients who received cetuximab plus chemotherapy survived longer than those who received chemotherapy alone (10.1 vs 7.4 months; hazard ratio [HR] for death, 0.80; P = .04).

The addition of cetuximab also significantly improved median progression-free survival (3.3 vs 5.6 months; HR for progression, 0.54; P < .001) and increased the response rate (20% vs 36%; P < .001).

“I think these data support the notion that we have a new standard treatment for patients with recurrent and/or metastatic head and neck cancer,” lead researcher Jan Vermorken, MD, PhD, professor of oncology at Antwerp University Hospital, in Ghent, Belgium, told Medscape Medical News when the study was published. “I would recommend that every patient with recurrent head and neck cancer who is not a candidate for radiation or surgery now receive platinum-based chemotherapy plus cetuximab, if their condition allows them to tolerate this.”

Higher Risk Adverse Events

The most commonly reported adverse events in patients who received cetuximab included rash, pruritus, nail changes, headache, diarrhea, and respiratory, skin, and mouth infections. The addition of cetuximab also increased the rate of sepsis, which occurred in 9 patients treated with chemotherapy plus cetuximab but in only 1 patient treated with chemotherapy alone (P = .02).

Cetuximab has also been known to cause low serum magnesium, potassium, and calcium; in this study, the incidence of hypomagnesemia also increased (11 patients treated with chemotherapy plus cetuximab and 3 treated with chemotherapy alone; P = .05). Other adverse events, such as neutropenia, were reported at similar rates in both groups, and the authors note that these adverse effects are consistent with the adverse-effect profile of cetuximab.

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

November, 2011|Oral Cancer News|

Cancer drug resistance strategy uncovered

Source: Cancer Research UK
Author: Staff

 

Friday 9 September 2011-

US scientists have identified a way in which cancer cells can become resistant to the cancer drug cetuximab (Erbitux), and suggest that treatments that are already available might be able to overcome this resistance.

Researchers from the Dana-Farber Cancer Institute in Boston, US, have been studying why some patients only experience short-term benefits with cetuximab, or none at all.

Cetuximab is an antibody that interferes with cancer cell growth. It can be given in combination with chemotherapy to patients with bowel cancer or head and neck cancer.

Until now, scientists didn’t know why some cancers failed to respond to the drug, or initially responded but then became resistant.

The new study, published in Science Translational Medicine, found that in some of the drug-resistant cells, a protein known as ErbB2 (also known as HER2/neu) was sending ‘grow’ signals.

These were bypassing the ‘stop growing’ signals caused by the drug.

Pasi Janne, the study’s co-senior author, said: “ErbB2 activates a critical signalling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab’s function.

“Because ErbB2 isn’t affected by cetuximab, this is an easy way for cancers to become resistant to the drug.”

The researchers suggest that combining cetuximab with already available ErbB2 inhibitors such as trastuzumab (Herceptin) could produce an effective therapy to tackle cancers that previously showed resistance to cetuximab.

Henry Scowcroft, science information manager at Cancer Research UK, said: “Unfortunately, patients’s tumours can become resistant to treatment, and understanding why this happens is a major challenge in cancer research.

“This new study is a great example of how researchers are uncovering the molecular tricks cancer cells use to evade treatment, and finding out how to stop them doing so.

“Research like this gives us tremendous optimism that we’re on the cusp of a real revolution in cancer, although there’s a lot more work to do to make this a reality.”

Copyright Press Association 2011

September, 2011|Oral Cancer News|

Strategy to conquer cancer drug resistance uncovered

Source: info.cancerresearchuk.org
Author: staff

US scientists have identified a way in which cancer cells can become resistant to the cancer drug cetuximab (Erbitux), and suggest that treatments that are already available might be able to overcome this resistance. Researchers from the Dana-Farber Cancer Institute in Boston, US, have been studying why some patients only experience short-term benefits with cetuximab, or none at all.

Cetuximab is an antibody that interferes with cancer cell growth. It can be given in combination with chemotherapy to patients with bowel cancer or head and neck cancer. Until now, scientists didn’t know why some cancers failed to respond to the drug, or initially responded but then became resistant.

The new study, published in Science Translational Medicine, found that in some of the drug-resistant cells, a protein known as ErbB2 (also known as HER2/neu) was sending ‘grow’ signals. These were bypassing the ‘stop growing’ signals caused by the drug.

Pasi Janne, the study’s co-senior author, said: “ErbB2 activates a critical signalling pathway that is not normally blocked by cetuximab, and in this way subverts cetuximab’s function.

“Because ErbB2 isn’t affected by cetuximab, this is an easy way for cancers to become resistant to the drug.”

The researchers suggest that combining cetuximab with already available ErbB2 inhibitors such as trastuzumab (Herceptin) could produce an effective therapy to tackle cancers that previously showed resistance to cetuximab.

Henry Scowcroft, science information manager at Cancer Research UK, said: “Unfortunately, patients’s tumours can become resistant to treatment, and understanding why this happens is a major challenge in cancer research.

“This new study is a great example of how researchers are uncovering the molecular tricks cancer cells use to evade treatment, and finding out how to stop them doing so.

“Research like this gives us tremendous optimism that we’re on the cusp of a real revolution in cancer, although there’s a lot more work to do to make this a reality.”

Reference:
Yonesaka, K. et al. (2011). Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab Science Translational Medicine, 3 (99), 99-99 DOI:10.1126/scitranslmed.3002442

September, 2011|Oral Cancer News|

Hypersensitivity Reactions to Erbitux Caused by Tick Bites.

Source: Gastroenterology & Endoscopy News

Hypersensitivity reactions to cetuximab (Erbitux, ImClone Systems/Bristol-Myers Squibb), a monoclonal antibody approved for use in colorectal cancer, are not caused by the drug itself but by preexisting immunoglobulin E (IgE) antibodies that may result from tick bites, researchers have found.

Cetuximab, like other monoclonal antibodies, is generally associated with a low rate of severe anaphylactic reactions (3%), but reports of such reactions to cetuximab have recently increased in southeastern states, including Tennessee and North Carolina. Researchers found IgE antibodies in pretreatment samples of 68% of patients allergic to cetuximab that were specific for galactose-α-1,3-galactose, an oligosaccharide present on the Fab portion of the cetuximab heavy chain.

The authors noted that rates of anaphylactic reaction may be lower with other monoclonal antibodies because cetuximab is produced in the mouse cell line SP2/0, which expresses this oligosaccharide, whereas most other monoclonal antibodies are produced in a Chinese hamster ovary cell line that does not express this molecule.

Theories to explain the increased hypersensitivity of patients in the Southeast initially centered on exposure to worms, such as roundworms or tapeworms. However, researchers now believe the true culprit may be ticks, whose bites have resulted in the development of this type of IgE antibody.

Pretreatment samples were obtained from 76 people treated with cetuximab at centers mainly in Tennessee, Arkansas and North Carolina; the control group included 72 people in Tennessee, 49 patients with cancer in northern California and 341 women in Boston. Of the patients on cetuximab, 25 had an allergic reaction to the drug, and IgE antibodies were found in pretreatment samples from 17 (68%) of them, whereas IgE antibodies were found in the pretreatment sample of only 1 (2%) of the 51 people on cetuximab who did not have an allergic reaction (P<0.001).

The authors believe it may be possible to test patients to determine whether they would be at greater risk for anaphylaxis with cetuximab. The ImmunoCAP assay used in the study to detect IgE antibodies has a sensitivity of 68% and a specificity of 98% for any hypersensitivity reaction; for especially severe reactions, its sensitivity was 92% and its specificity was 90%. However, the assay is in development and not currently available commercially.

—Based on Chung CH et al (N Engl J Med 2008;358:1109-1117)

This news story was resourced by the Oral Cancer Foundation, and vetted for appropriateness and accuracy.

HPV and EGFR are hottest topics in head and neck cancer

Source: www.medscape.com
Author: Zosia Chustecka

The hottest topic in head and neck cancers is the role of human papillomavirus (HPV) in the disease, although there is also a lot interest in treatment with EGRF inhibitors, especially the second-generation products, according to an expert here at the European Society for Therapeutic Radiology and Oncology 11th Biennial Conference.

HPV has only been associated with head and neck cancer in the last few years, but it is now clear that patients who are positive for the virus have a better prognosis, said Cai Grau, MD, DMSC, professor of oncology at Aarhus University Hospital, Denmark. He chaired a session during which both hot topics were discussed.

“These patients have a better prognosis, irrespective of treatment, and their risk of a second cancer is virtually zero,” added session participant Lisa Licitra, MD, medical oncologist at the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan, Italy.

However, there is a difference between patients in the United States and those in Europe with regard to risk, she told meeting attendees.

For American patterns, Dr. Licitra cited the analysis published last year in the New England Journal of Medicine (2010;363:24-35), which reported a risk model for death from oropharyngeal squamous cell carcinoma on the basis of HPV status, pack-years of tobacco smoking, and tumor and nodal stage. In this 266-patient cohort, 43% were low risk, 30% were intermediate risk, and 27% were high risk.

Dr. Licitra reported that when she performed the same analysis on a cohort of 120 patients at her institution, the percentages were different — among the Italian patients, 22% were low risk, 38% were intermediate risk, and 40% were high risk.

“There were more high-risk and fewer low-risk patients,” she pointed out, and speculated in an interview that this might be because of higher rates of smoking in Italy.

These differences in risk estimates might account for differences in outcomes between European and American patients in international trials of head and neck cancer, Dr. Licitra said. For instance, this was seen in a trial by Bonner et al (N Engl J Med. 2006:354;567-578), which showed that the EGRF inhibitor cetuximab (Erbitux) added to radiotherapy was an effective option in head and neck cancer.

The European patients in the Bonner trial fared worse than the American patients, and there has been a lot of speculation as to why, she noted in an interview. There were suggestions that radiotherapy improved outcomes in the United States, for example. But the new data reported by Dr. Licitra suggest another potential explanation: the European patients might have had worse outcomes because more were negative for HPV and at higher risk for recurrence. “We now appreciate that the patient population is different,” she explained.

However, she emphasized that this is speculation; the participants of the Bonner trial were not tested for HPV status.

Going forward, clinical trials of patients with head and neck cancer are now stratifying for HPV status, Dr. Licitra and Dr. Grau both noted.

Less Intense Therapy?

One of the issues being explored is whether the management should be different for head and neck cancer patients who are positive for HPV. There is a suggestion that, because of their better prognosis, these patients could undergo less intense therapy.

However, so far “the scientific evidence for this is not strong,” Kevin Harrington, FRCP, FRCR PhD, senior lecturer at the Institute of Cancer Research, and honorary consultant oncologist at the Royal Marsden Hospital, London, United Kingdom, told meeting attendees.

Standard treatment for head and neck cancer is chemoradiation, which is supported by level 1a evidence from controlled randomized clinical trials, he noted. The gold standard is single-agent cisplatin with radiotherapy.

There are data that show that HPV-positive patients have a significantly better outcome than HPV-negative patients, deriving about 35% greater benefit, he said. “But it is difficult to suggest abandoning chemoradiation,” he said. There might be a case for replacing cisplatin with a less toxic chemotherapeutic and/or deescalating the radiation dose, he added.

EGFR inhibitors such as cetuximab offer another therapy option. Clinical trials so far have added cetuximab to radiotherapy (as the Bonner trial did) and added cetuximab to chemoradiotherapy. This option is attractive because these drugs are oral and less toxic than chemotherapy such as cisplatin. As a result, there has been a separate trend within head and neck cancer to assess tumors for EGRF-receptor expression.

Initially, there was hope that the patients with HPV-positive tumors, who have a better prognosis, would be the patients who would respond best to treatment with EGRF inhibitors, and thus avoid chemotherapy, Dr. Grau explained.

However, there appears to be little interaction between HPV and EGFR inhibitors, Dr. Harrington said. “We were looking to see if HPV and EGFR are talking to one another,” he said, but “there is no evidence in the medical literature that they are interacting at a molecular or mechanistic level.”

The data do not support the notion that patients who have HPV-positive tumors are good candidates for treatment with EGFR inhibitors, he said.

Currently, chemoradiation with single-agent cisplatin remains the gold standard treatment for head and neck cancer. This is the treatment against which all new options will be measured, Dr. Harrington noted.

An ongoing trial (NCT00820248) is the first head-to-head trial to test the standard treatment of cisplatin with radiotherapy against a newer option — radiotherapy combined with the second-generation EGRF inhibitor panitumumab, he said.

Note:
1. Zosia Chustecka is the News Editor for Medscape Oncology.

ASCO: Non-platinum regimen works in head, neck cancer

Source: www.medpagetoday.com
Author: Michael Smith, North American Correspondent, MedPage Today

A novel non-platinum-based regimen was efficacious in recurrent or metastatic squamous cell head and neck cancer, researchers said. The combination of pemetrexed (Alimta) and bevacizumab (Avastin) yielded a response rate of 30% in a small single-arm trial, according to Athanassios Argiris, MD, of the University of Pittsburgh, and colleagues.

The combination also increased the length of time before patients progressed, and increased median overall survival, Argiris and colleagues reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here.

Patients with recurrent or metastatic disease typically have a poor prognosis, the researchers said, with median survival between six and nine months with standard chemotherapy. But, in other research, adding the monoclonal antibody cetuximab (Erbitux) to platinum-based chemotherapy increased survival, they said.

Bevacizumab is a monoclonal antibody that targets the vascular epithelial growth factor (VEGF), which is expressed in squamous cell head and neck cancer; high levels of VEGF correlate with poor outcome, they noted.

The researchers hypothesized that the antibody might enhance the activity of pemetrexed, which is a multi-targeted antifolate indicated for malignant pleural mesothelioma and non-small cell lung cancer.

To test the idea, they analyzed results of treating 37 patients given 500 mg/m2 of pemetrexed and 15 mg/kg of bevacizumab intravenously every 21 days until disease progression. Patients were also given folic acid and vitamin B12.

The primary endpoint of the study was time to progression, they said, but the researchers also isolated DNA from 28 patients to see if genetic variations played a role in survival.

Analysis showed:

  • Two patients had a complete response and 11 had a partial response, for a response rate of 30%. As well, 21 patients had stable disease for a disease control rate of 86%.
  • The median time to progression was 4.9 months.
  • Median overall survival was 11.5 months.
  • Bleeding events of grade two or greater occurred in six patients, including four that were grade three and two that were fatal.

The researchers said that it is difficult to know whether the bleeding was associated with the drugs or was part of the natural history of the disease.

The DNA analysis showed that a single nucleotide polymorphism (SNP) in the gene for methylenetetrahydrofolate reductase was associated with significantly worse overall survival, although no other tested variants had significant associations.

Patients with two copies of the A variant in the MTHFR A1298C polymorphism had a median overall survival of 4.2 months, compared with 32.8 months for those with other variants. The difference was significant at P=0.006, the researchers said.

The “data are favorable” compared with other non-platinum regimens, according to Ranee Mehra, MD, of Fox Chase Cancer Center in Philadelphia, who was not involved in the research but who discussed it in an oral session. But she noted that the impact of second-line therapy on overall survival remains unclear, especially since some patients may have gone on to platinum-based regimens, which might have affected their outcomes.

That said, she added, “bevacizumab is a novel agent in squamous cell head and neck cancer that has a favorable response rate.”

Larger – and randomized — trials are needed to define the extent of any benefit, she said, adding that one such trial – Eastern Cooperative Oncology Group 13056 – is currently underway.

Source:
1. Journal of Clinical Oncology
2. Argiris A et al. “Pemetrexed (P) and bevacizumab (B) in patients (pts) with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): Final results and correlation with TS, MTHFR, and VEGF gene polymorphisms.” J Clin Oncol 28:7s, 2010 (suppl; abstr 5533)

ASCO: Antibody improves head and neck cancer results

Source: www.medpagetoday.com
Author: Michael Smith, North American Correspondent, MedPage Today

A novel antibody improved outcomes for patients with advanced and inoperable squamous cell carcinoma of the head and neck, researchers reported.

Combined with radiation or chemoradiation, the substance — a fully humanized monoclonal antibody dubbed nimotuzumab — significantly outperformed either modality alone in an open-label randomized trial, according to K. Govind Babu, MD, of Kidwai Memorial Institute of Oncology in Bangalore, India, and colleagues.

At the same time, there was little serious toxicity — such as debilitating skin rash — attributed to the compound, the researchers reported in a poster discussion session at the annual meeting of the American Society of Clinical Oncology here.

It’s the first randomized study of the drug to show clinical benefit without the toxicities associated with similar antibodies, the researchers said.

In general, neither radiation nor chemotherapy provides a good outcome for patients with inoperable stage III or IVa squamous cell carcinoma of the head and neck. However, substances such as cetuximab (Erbitux) that target the epidermal growth factor receptor (EGFR) — overexpressed in such tumors — have improved outcomes.

Nimotuzumab, like cetuximab, targets EGFR, but is highly selective for tumor tissues, limiting toxicity, the researchers said.

The study enrolled 92 patients, and 76 were evaluable for efficacy. They were treated with radiation or chemoradiation (with cisplatin), with or without nimotuzumab. The substance was given by intravenous infusion of 200 milligrams over a 60-minute period, once a week for six weeks.

In group A — radiation with or without the antibody — the locoregional response rate was 37% with radiation alone, but was 76% when nimotuzumab was added, the researchers reported. In the other group, chemoradiation and nimotuzumab led to a 100% locoregional response, compared with 70% for chemo alone, they said.

At four years of follow-up, they reported:

  • The overall survival rate was 47% for patients getting the antibody and chemoradiation, compared with 21% for chemoradiation alone, a difference that was significant at P=0.01.
  • The comparable rates in the radiation group were 34% for the combination and 13% for radiation alone, which were not significantly different.
  • Median overall survival was not reached for chemoradiation and nimotuzumab, but was 21.9 months for chemoradiation alone. The comparable figures for radiation were 14.3 months versus 12.7 months.
  • Adding nimotuzumab to chemoradiation resulted in a 65% reduction in risk of death; the hazard ratio was 0.35, which was significant at P=0.01.

The study was small, but it provides a “signal of benefit” that needs to be confirmed in larger randomized trials, according to Ranee Mehra, MD, of Fox Chase Cancer Center in Philadelphia, who was not involved in the research but who discussed it in an oral session.

She noted that the arms of the trial were imbalanced in terms of the cancer site, with a higher percentage of cancer of the oropharynx in the nimotuzumab arms.

Mehra said the results in the radiation arm don’t parallel historical data with cetuximab. In trials with that substance, the median overall survival with radiation was 29 months, and when cetuximab was added it reached 49 months.

The differences have several possible explanations, she said, including varying patient characteristics, a lower radiation dose in the nimotuzumab trial, and the effect of human papillomavirus infection, which was not recorded in this study but which plays a role in outcomes.

Source:

1. Journal of Clinical Oncology
2. Babu KG et al. “An open-label, randomized, study of h-R3mAb (nimotuzumab) in patients with advanced (stage III or IVa) squamous cell carcinoma of head and neck (SCCHN): Four-year survival results from a phase IIb study.” J Clin Oncol 28:7s, 2010 (suppl; abstr 5530)

Presence of rash associated with improved survival in patients receiving adjuvant Erbitux® for locally advanced head and neck cancer

Source: professional.cancerconsultants.com
Author: staff

A multicenter randomized trial has shown that patients with locoregionally advanced head and neck cancer receiving adjuvant Erbitux® (cetuximab) and radiotherapy who develop a rash have a better survival than patients receiving this therapy who don’t develop a rash. The details of this five-year follow-up of a Phase III randomized study were published early online in the Lancet Oncology on November 7, 2009.[1]

Standard treatment for head and neck cancer is largely determined by the stage and by the specific locations within the head or neck area where the cancer has spread. The patient’s overall medical condition is also a deciding factor. Treatment typically consists of radiation therapy, chemotherapy with surgery, or surgery alone.

Erbitux is a monoclonal antibody that binds to the epithelial growth factory receptor (EGFR) and inhibits the receptor’s effects on cellular replication. Erbitux is currently FDA-approved for treatment of head and neck cancer. Researchers involved in an international study have previously reported that the addition of Erbitux to radiation therapy improves survival over radiation therapy alone in the treatment of head and neck cancer. The results of this randomized trial with a 54-month follow-up were published in the February 9, 2006, issue of the New England Journal of Medicine. This trial included 424 patients; approximately half were treated with Erbitux plus high-dose radiation therapy, and the other half received high-dose radiation therapy alone. This study now has a follow-up of more than five years.

The Following table summarizes some of the findings of this trial.

Table 1: Effect of the Addition of Erbitux to Radiotherapy in Head and Neck Cancer

table

Rash and reactions at the site of infusions were the most common side effects experienced by patients treated with Erbitux. Patients receiving Erbitux who experience a rash had 51% improvement in overall survival compared with patients receiving Erbitux without a rash.

The researchers concluded that the addition of cetuximab to radiation therapy is well tolerated and improves overall survival compared with radiation therapy alone in the treatment of patients with head and neck cancer.

Comments: This study with a longer follow-up demonstrates the lasting effect of adding Erbitux to radiotherapy for treatment of head and neck cancer. The association of rash with an increased response is of major interest.

Reference:
[1] Bonner JA, Harari PM, Giralt J, et al. Radiotherapy plus cetuximab for locoregionally advanced head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between cetuximab-induced rash and survival. Lancet Oncology [early online publication]. November 7, 2009.

November, 2009|Oral Cancer News|