ORLANDO-Results from an international phase III trial in advanced non-small-cell lung cancer could change the standard of care, according to the lead investigator.
ORLANDO-Results from an international phase III trial in advanced non-small-cell lung cancer could change the standard of care, according to the lead investigator. Chandra Belani, MD, predicted that the findings could lead to a new treatment paradigm, but another expert said he remains unconvinced of the benefits of immediate vs delayed pemetrexed.
Dr. Belani reported at ASCO 2009 that maintenance therapy with pemetrexed (Alimta) significantly improved overall survival in NSCLC. “This is the first randomized double-blind placebo-controlled study to show the benefit of pemetrexed in the maintenance setting after initial therapy,” Dr. Belani said at a press conference. He is the deputy director of the Penn State Cancer Institute in Hershey.
The randomized, double-blind study included 441 patients treated with pemetrexed 500 mg/m2 every 3 weeks plus best supportive care and 222 patients treated with placebo plus best supportive care.
All study patients had advanced or metastatic (stage IIIB or IV) NSCLC that had not progressed after four cycles of platinum-based chemotherapy. Pemetrexed was continued until disease progression (abstract CRA8000).
Overall survival was 13.4 months for the pemetrexed maintenance group, compared with 10.6 months for the placebo group, representing a 21% reduction in risk (P = .012). Median progression-free survival was four and two months, respectively, for a 40% reduction in risk with pemetrexed (P < .00001). The percentage of patients obtaining clinical benefit was 51.7% and 33.3%, respectively (P < .001).
The researchers did note that the benefit was limited to nonsquamous histology. In patients with nonsquamous histology, overall survival was 15.5 months with pemetrexed vs 10.3 months with placebo, for a 30% reduction in risk (P = .002). The difference in patients with squamous histology was not significant, 9.9 months vs 10.8 months.
Maintenance pemetrexed was “fairly well tolerated,” Dr. Belani said. Only 5% of patients required dose reductions. Pemetrexed-treated patients had more grade 3 and 4 neutropenia (3% vs 0%) and fatigue (5% vs 1%).
Expert not persuaded
Commenting on the study to Oncology News International, Lawrence Einhorn, MD, said that the pemetrexed data did not persuade him and that he does not advocate maintenance chemotherapy in NSCLC. “The way to answer that question is by randomizing patients to immediate vs delayed pemetrexed,” said Dr. Einhorn who is the Lance Armstrong Foundation Professor of Oncology at Indiana University in Indianapolis.
“We know that pemetrexed helps patients live longer. It improved survival in this study, but this may not have been due to giving immediate pemetrexed, but because of the study design, in which 81% of the patients were unable to receive the drug in some countries and only 19% crossed over,” he explained. “In my own practice, there are not 81% of patients who progress and do not get it at all.”
Dr. Einhorn also mentioned that the cost of adding pemetrexed could be considerable. “Is it right to give patients therapy that is expensive when it has not been proven that you can’t get the same survival benefit by delaying treatment?” he asked. n