FIRST MAINTENACE THERAPY FOR ADVANCED LUNG CANCER APPROVED BY THE FDA

July 6, 2009 — The US Food and Drug Administration (FDA) has approved pemetrexed (Alimta, Eli Lily) for the maintenance therapy of advanced or metastatic nonsquamous non–small-cell lung cancer (NSCLC). Pemetrexed is the first drug indicated as a maintenance therapy in this setting.

"This drug represents a new approach in the treatment of advanced non–small-cell lung cancer," said Richard Pazdur, MD, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, in a press statement. "Typically, patients whose tumors respond to chemotherapy do not receive further treatment after four to six chemotherapy cycles. This study demonstrates an advantage in overall survival in certain patients who received Alimta for maintenance therapy."

In a phase 3 trial recently presented at the American Society of Clinical Oncology (ASCO) meeting, patients received either pemetrexed (n = 441) or placebo (n = 222), along with the best supportive care. Patients had advanced or metastatic (stage 3B or 4) NSCLC (both squamous and nonsquamous subtypes) that had not progressed after 4 cycles of initial platinum-based chemotherapy.

For all patients in the study, the pemetrexed treatment group had an overall survival of 13.4 months, compared with 10.6 months for the placebo group. However, for the nonsquamous subgroup, overall survival was 15.5 months for patients taking pemetrexed and 10.3 months for patients taking placebo. The difference was statistically significant (P = .002).

However, as reported by Medscape Oncology from ASCO, 2 lung-cancer experts attending the meeting questioned the appropriateness of using pemetrexed as a maintenance therapy. Neither was involved with this phase 3 trial.

"I don't think we have the answer as to when it is best to start pemetrexed. Should we start immediately after standard chemotherapy or later on? All you can say is that it improves survival in nonsquamous-cell patients. In my clinic, I will present maintenance therapy as an option," said Julie Brahmer, MD, from the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, in Baltimore, Maryland.

"I endorse the use of pemetrexed as a second-line therapy for advanced non–small-cell lung cancer, but I don't think that all patients need immediate maintenance therapy following first-line treatment," said Nasser H. Hanna, MD, from the department of medicine at Indiana University, in Indianapolis, adding that the trial design did not allow it to definitively establish pemetrexed as a maintenance therapy.

Dr. Hanna explained the phase 3 trial was not designed to indicate whether maintenance therapy was superior to using pemetrexed at time of disease progression.

"Only 19 patients who were on placebo received pemetrexed at time of disease progression because, in part, the drug was not available at all of the centers involved in the study. In short, we know the drug improves survival but not that maintenance therapy is the best way to use it," he said.

A form of chemotherapy, pemetrexed is a folate analog metabolic inhibitor, which means that it disrupts metabolic processes that depend on the B-vitamin folate, a necessary ingredient for cell replication.

In the phase 3 study presented at ASCO, severe adverse effects (grade 3 or 4) were more common in the pemetrexed than in the placebo group, including fatigue (5% vs 0.5%) and low white-blood-cell counts (2.9% vs 0%).

Other reported adverse events included nausea, loss of appetite, tingling or numbness in the hands and feet, and skin rash, according to the FDA statement.