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.