The FDA expanded the labeling of pemetrexed (Alimta, Eli Lilly and Company) to include the results of an additional trial evaluating its safety and efficacy for the initial treatment of patients with locally advanced or metastatic, nonsquamous, non‒small cell lung cancer followed by pemetrexed maintenance in patients with disease that has not progressed after 4 cycles of platinum and pemetrexed as first-line chemotherapy. The approval for expanded labeling was granted on October 17, 2012.
The expanded labeling describes the results of a multicenter, randomized (2:1), double-blind, placebo-controlled trial that evaluated pemetrexed maintenance in patients with stage IIIB/IV nonsquamous, non‒small cell lung cancer whose initial treatment was 4 cycles of pemetrexed plus cisplatin. There were 539 patients randomized to receive 500 mg/m2 pemetrexed intravenously on day 1 of each 21-day cycle (359 patients) or matching placebo (180 patients). All patients had an ECOG performance status of 0 or 1 and had completed 4 cycles of pemetrexed plus cisplatin with a best response of stable disease, partial response, or complete response.
Investigator-assessed progression-free survival (PFS) was significantly improved in patients randomized to receive pemetrexed maintenance, compared with those who received placebo. Median PFS was 4.1 months for patients in the pemetrexed arm and 2.8 months for patients receiving placebo. Overall survival, a secondary end point, also was significantly improved for patients receiving pemetrexed maintenance, with median survival time of 13.9 months, compared with 11.0 months for patients receiving placebo.
Neutropenia, anemia, fatigue, nausea, vomiting, stomatitis, and edema were the most common (>5%) adverse events for patients in the pemetrexed arm. Anemia and neutropenia were the most common severe adverse reactions. Approximately 25% of patients receiving pemetrexed maintenance had treatment reduced or delayed because of toxicity.