FDA Expands Labeling of Pemetrexed
Wednesday, October 17, 2012
The U.S. Food and Drug Administration expanded labeling to include the results of an additional trial evaluating the safety and efficacy of pemetrexed (ALIMTA®, Eli Lilly and Company) for the initial treatment of patients with locally advanced or metastatic, non-squamous, non-small cell lung cancer followed by pemetrexed maintenance in patients whose disease has not progressed after four cycles of platinum and pemetrexed as first-line chemotherapy.
Pemetrexed is currently approved, in combination with cisplatin therapy, for the initial treatment of patients with locally advanced or metastatic non-squamous, non-small cell lung cancer and for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. Pemetrexed is not indicated for the treatment of patients with squamous cell lung cancer.
The additional trial now described in product labeling is a multi-center, randomized (2:1), double-blind, placebo-controlled trial evaluating pemetrexed maintenance in patients with Stage IIIB/IV non-squamous non-small cell lung cancer whose initial treatment was four cycles of pemetrexed plus cisplatin.
Patients with ECOG performance status 0 or 1 who completed 4 cycles of pemetrexed plus cisplatin with a best response of either stable disease, partial response or complete response were randomized to receive either pemetrexed 500 mg/ m2 intravenously on day 1 of each 21-day cycle or matching placebo until disease progression. Patients in both study arms also received folic acid and vitamin B12 supplementation for the duration of maintenance treatment and dexamethasone prior to, on the day of, and the day following pemetrexed administration. The primary efficacy outcome was investigator-assessed progression-free survival (PFS).
A total of 539 patients were randomized; 359 patients to pemetrexed and 180 to placebo. Fifty-eight per cent of patients were male, 78% were smokers/former smokers, 87% had adenocarcinoma histology, 68% had ECOG performance status of 1, and 91% had stage IV disease.
A significant improvement in investigator-assessed PFS was observed in patients randomized to receive pemetrexed maintenance compared to those receiving placebo [HR 0.62 (95% CI: 0.49 to 0.79); p < 0.0001]. The median PFS was 4.1 and 2.8 months for patients receiving pemetrexed and placebo, respectively. A significant improvement in overall survival, a key secondary endpoint, was also observed for patients randomized to pemetrexed maintenance compared to those on the placebo arm [HR 0.78 (95% CI: 0.64 to 0.96) p=0.02)]. The median survival times were 13.9 and 11.0 months for patients receiving pemetrexed and placebo, respectively.
Patients received a median of 4 cycles of maintenance in both arms. Treatment was reduced or delayed in approximately 25% of patients in the pemetrexed arm due to toxicity. The most common (>5%) adverse reactions in patients receiving pemetrexed maintenance in this trial were neutropenia, anemia, fatigue, nausea, vomiting, stomatitis and edema. The most common severe adverse reactions were anemia and neutropenia; 13% of patients received red blood cell transfusions, 12% erythropoiesis-stimulating agents, 6% granulocyte colony-stimulating factors, and 1.5% platelet transfusions.
Full prescribing information is available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021462s039lbl.pdf
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).