Primary source: Journal of the National Cancer Institute

Source reference:

Hershman D, et al “Patterns of use and risks associated with erythropoiesis-stimulating agents among Medicare patients with cancer” J Natl Cancer Inst 2009; DOI: 10.1093/jnci/djp387.

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New recommendations on the use of chemotherapy to treat patients with stage 4 non-small cell lung cancer (NSCLC) were issued today by the American Society of Clinical Oncology (ASCO).

The evidence-based clinical practice guideline indicates a patient’s physical age should not determine the cancer treatment he/she is given. Instead, ASCO recommends oncologists take other factors into account including physiological age and performance status when determining appropriate treatment for stage 4 NSCLC patients.

The new guideline also makes specific recommendations for first-line treatment of NSCLC including:

- Cisplatin (Platinol) or carboplatin (Paraplatin) may be used for first-line chemotherapy in combination with a second drug, such as docetaxel (Alimta) or vinorelbine (Navelbine).

- Bevacizumab (Avastin) is recommended with carboplatin plus paclitaxel in particular circumstances.

- Physicians may consider adding cetuximab (Erbitux) to cisplatin plus vinorelbine in first-line therapy in patients with a tumor which tests positive for EGFR protein.

- Gefitinib (Iressa) may be used as first-line therapy in patients with a tumor which tests positive for an activating EGFR gene mutation.

Recommendations for second-line and third-line treatment include:

- For second-line treatment, the guideline recommends the use of a single drug, eitherdocetaxel, erlotinib, gefitinib or pemetrexed.

- For third-line treatment, the guideline recommends erlotinib if a patient’s performance status is 0 to 3 and he/she has not previously received erlotinib or gefitinib.

While patients with a tumor that tests positive for an EGFR mutation may receive certain drugs which target EGFR earlier in the course of their disease, the guideline does not recommend the routine use of molecular markers to choose treatment for patients with NSCLC because there is not enough evidence that doing so extends patients’ lives.

“The use of molecular markers in treating people with cancer is a rapidly developing field with interesting potential,” said Giuseppe Giaccone, MD, PhD, co-chair of the guideline expert panel and a physician and researcher with the National Cancer Institute. “ASCO is diligently monitoring clinical research involving the use of biomarkers to personalize the treatment of patients with NSCLC to ensure that its guidelines reflect all available high quality evidence.”

The updated guideline also highlights disparities in treating members of minority populations who are diagnosed with lung cancer. Research has shown that only 36 percent of African Americans with stage 4 NSCLC receive first-line chemotherapy. Reasons for these disparities include socio-economic status, access to health services, other existing medical conditions and ineffectual communication between health care providers and patients.

“Ethnic and racial minorities experience worse outcomes compared to whites in all stages of lung cancer, and these disparities are frequently due to communication barriers between doctors and their patients,” said Christopher G. Azzoli, MD, co-lead author of the guideline and physician at the Memorial Sloan-Kettering Cancer Center in New York City. “When patients receive uniform clinical care, these disparities are minimized.”

Lung cancer is the leading cause of cancer deaths for men and women in the United States, and it is estimated that 159,390 people will die from lung cancer (88,900 men and 70,490 women) in 2009. NSCLC is the most common type of lung cancer, and a stage 4 diagnosis means that the cancer has spread to the opposite lung, and/or to distant sites within the body by way of the bloodstream and is no longer operable. Once released in the blood, NSCLC can spread anywhere in the body, but has a tendency to spread to the brain, bones, liver, and adrenal glands.

ASCO published its first evidence-based clinical practice guideline on treating NSCLC in 1997 and published an update in 2003. In conjunction with the latest update published today, ASCO has developed clinical tools and resources for oncologists that summarize the findings and recommendations. These resources include Decision Aid Tools to help physicians and patients have a better dialogue on the potential benefits, risks, and prognosis of treating stage 4 non-small cell lung cancer with chemotherapy, as well as a slide presentation and a summary in the Journal of Oncology Practice.

The updated clinical practice guideline, decision aid tools, and other resources are available at http://www.asco.org/guidelines/nsclc. ASCO also has developed a corresponding patient guide available on ASCO’s patient web site, http://www.cancer.net.

This guideline is being published in the November 16 issue of the Journal of Clinical Oncology (JCO), the semi-monthly peer-reviewed journal of the American Society of Clinical Oncology (ASCO), the world’s leading professional society representing physicians who treat people with cancer.

Source
American Society of Clinical Oncology

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WASHINGTON — An FDA advisory panel voted against recommending approval for erlotinib (Tarceva) for advanced non-small-cell lung cancer (NSCLC) patients who are stable following chemotherapy.

Erlotinib is already approved to treat NSCLC as a second-line therapy if chemotherapy fails to stop the cancer from spreading.

Erlotinib’s manufacturer, OSI Pharmaceuticals, sought approval for patients whose disease remains stable following chemotherapy, but the Oncologic Drugs Advisory Committee voted 12 to 1 on Wednesday that erlotinib should not be approved as a first-line treatment.

The FDA does not have to follow the advice of its advisory committees, but it usually does.

In the company’s trial, researchers randomized 889 locally advanced or metastatic NSCLC patients to receive either erlotinib tablets or placebo following four cycles of chemotherapy.

The study found that erlotinib was superior to placebo for both primary endpoints: overall survival in all patients and overall survival in patients positive for epidermal growth factor receptor (EGFR) mutations, measured by immunohistochemistry (P=0.0001 for both).

However, the drug did not extend survival among EGFR negative patients and in those with squamous cells, raising the question of whether erlotinib should be approved as a maintenance therapy in those two groups, according to FDA documents released in advance of Wednesday’s hearing.

But the main issue, according to FDA, reviewers “concerns other available treatment options.”

Another drug, docetaxel (Taxotere), is also approved to treat NSCLC in the case of chemotherapy failure. Both erlotinib and docetaxel improve median survival by about three months compared with placebo, but erlotinib only improves survival by about one month when used as a first-line therapy, according to the FDA.

“This raises the question whether treatment with single agent erlotinib or docetaxel after progression are better options than treatment with erlotinib as maintenance,” the reviewers wrote.

Pemetrexed (Alimta) is the only drug approved for maintenance treatment of patients with locally advanced or metastatic NSCLC whose disease has not progressed after four cycles of chemotherapy.

But it is only approved for patients with nonsquamous cell cancer.

The European Medicines Agency has been formally notified by AstraZeneca of its decision to withdraw its application for a centralised marketing authorisation for the medicine Zactima (vandetinib), 100 mg film-coated tablets.

Zactima was expected to be used in combination with chemotherapy, for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received prior anticancer therapy.

The application for the marketing authorisation for Zactima was submitted to the Agency on 30 June 2009. At the time of the withdrawal, it was under review by the Agency’s Committee for Medicinal Products for Human Use (CHMP).

In its official letter, the company stated that the withdrawal of the application was based on the preliminary comments from the Rapporteur and Co-Rapporteur, which indicate that at this point in time the Committee would be unlikely to conclude on a favourable benefit-risk balance for the product in the treatment of NSCLC in combination with chemotherapy.

More information about Zactima and the state of the scientific assessment at the time of withdrawal will be made available in a question-and-answer document. This document, together with the withdrawal letter from the company, will be published on the Agency’s website after the next CHMP meeting of 16-19 November 2009.

Notes

1. Withdrawal of an application does not prejudice the possibility of a company making a new application at a later stage.

Source
EMEA

Cancer patients treated with the widely used drug bevacizumab (Avastin) in combination with chemotherapy are at greater risk of life-thereatening gastrointestinal (GI) perforations. This is the conclusion of Shenhong Wu, M.D., Ph.D., Principal Investigator, and colleagues at Stony Brook University Medical Center, in a study published online and in the June print issue of The Lancet Oncology.

Bevacizumab is an angiogenesis inhibitor that slows down the growth of tumors by cutting off their blood supply. The agent has been shown to be effective in treating many forms of cancer, including colorectal cancer, renal cell cancer, non-small cell lung cancer and breast cancer. There has been concern about the use of bevacizumab and GI perforations, which are dangerous holes that develop in the stomach, small intestine or large bowel. The U.S. Food and Drug Administration has issued a black-box warning to discontinue bevacizumab in patients with GI perforations. However, a link between the use of bevacizumab in cancer patients and GI perforations had not been established until the SBUMC study results.

“Our study establishes a significant association between the use of bevacizumab in cancer patients and the risk for GI perforations, one in which the risk of GI perforations was double that in those taking the medication compared to those taking a control medication,” says Dr. Wu, Assistant Professor of Medicine in the Division of Hematology/Oncology. “We hope the study results will help to identify a subset of patients receiving bevacizumab at high risk of bevacizumab-associated perforation.”

In “Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis,” Dr. Wu and colleagues completed a systematic review and meta-analysis of 17 randomized controlled trials involving 12,294 patients with various types of solid tumors to assess the role of bevacizumab in GI perforation. The overall incidence of GI perforation among patients receiving bevacizumab was 0.9%. Of those patients with a GI perforation, the mortality rate was extremely high at 21.7 percent.

The study results revealed that risk varied with bevacizumab dose and tumor type. The higher the dose of the agent, the greater the risk for GI perforation. Patients taking 2.5 mg/kg per week of bevacizumab were 61 percent more likely to have a perforation. Patients receiving the highest dose (5 mg/kg per week) had a 167 percent higher risk. The highest risks for GI perforation were found in patients with advanced colorectal cancer and renal cell cancer. The lowest risk was in patients with pancreatic cancer.

The authors believe that because bevacizumab is extensively used in routine cancer treatment and the risk for GI perforation is significant in patients, it is increasingly important to recognize symptoms indicating perforation and intervene to reduce morbidity and mortality. In addition, they recommend further studies to “investigate risk reduction, and the possible use of bevacizumab in selected patients who have recovered from GI perforation.”

Dr. Wu’s co-authors at SBUMC include Sanjaykumar Hapani, M.D., and David Chu, M.D. The study was funded in part by the Stony Brook University Research Foundation.

Source: Stony Brook University Medical Center

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