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Pemetrexed maintenance therapy improved OS in NSCLC
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Patients with non–small cell lung cancer who received pemetrexed maintenance therapy experienced significantly longer OS than those who received placebo, according to results of the phase 3 PARAMOUNT study.
The trial included 939 patients with advanced nonsquamous NSCLC who received four cycles of an induction therapy of pemetrexed (Alimta, Eli Lilly) and cisplatin.
The 539 patients with no disease progression and ECOG performance status 0 or 1 were eligible for the maintenance treatment.
Researchers randomly assigned 359 patients to maintenance therapy with pemetrexed (500 mg/m2 on the first day of each 21-day cycle). The other 180 patients received placebo.
The mean number cycles for the treatment group was 7.9 (range, 1-44) and 5 for the placebo group (range, 1-38).
At mean follow-up of 24.3 months, researchers determined pemetrexed was associated with a 22% reduction in risk for death (HR=0.78; 95% CI, 0.64-0.96). Median OS was 13.9 months in the pemetrexed arm vs. 11 months in the placebo arm.
Among patients in the pemetrexed arm, OS did not differ between the 234 patients with complete response to induction therapy (HR=0.81; 95% CI, 0.59-1.11) or the 285 patients with stable response to induction therapy (HR=0.76; 95% CI, 0.57-1.01).
Rates of drug-related grade 3/4 anemia, fatigue and neutropenia were significantly higher in the pemetrexed arm; hwoever, no new safety findings emerged, according to researchers.
“Pemetrexed continuation maintenance therapy is well tolerated and offers superior OS compared with placebo, further demonstrating that it is an efficacious treatment strategy for patients with advanced nonsquamous NSCLC and good performance status who did not progress during pemetrexed-cisplatin induction therapy,” the researchers concluded.
Perspective
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Eric H. Bernicker, MD
The best maintenance approach for patients with metastatic NSCLC remains an active research question, but the important final results of the PARAMOUNT study by Paz-Ares and colleagues help clarify a number of issues.
In the study, more than 900 patients with advanced nonsquamous NSCLC with good performance status and nonprogression after induction therapy with pemetrexed-cisplatin were randomly assigned to continuation maintenance with pemetrexed or placebo. Overall, the therapy was well tolerated and the active arm saw a significant improvement in both PFS and OS.
Median OS was 13.9 months in the pemetrexed group versus 11 months with placebo; 32% of patients in the treatment arm were alive at 2 years vs. 21% of those assigned to placebo.
Yet many questions remain. Is the best strategy to utilize continuation maintenance by keeping the patient on an agent used in induction, or should a different agent be brought in, as switch maintenance prescribes? Should the maintenance arm be a single drug (pemetrexed or bevacizumab [Avastin, Genentech]) or a combination, such as what was looked at in the AVAPERL trial?
While we all await the results of ECOG 5508, which is looking at bevacizumab vs. pemetrexed vs. both in maintenance, that study utilizes a different induction chemotherapy backbone with paclitaxel. In the meantime, what should clinicians recommend to their patients?
I think that, in patients with nonsquamous NSCLC and a good performance status after four cycles of induction chemotherapy, there is little doubt that maintenance therapy with pemetrexed with or without bevacizumab is well tolerated and prolongs meaningful survival and should be offered. It will be left to further trials to better understand the relationship of maintenance therapy to the particular induction backbone and to hopefully discover biomarkers that identify patients who are likely to benefit — or not benefit — from therapy.
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