Pemetrexed maintenance therapy prolonged PFS in advanced NSCLC

Issue: July 10, 2011

2011 ASCO Annual Meeting

CHICAGO — Continuation maintenance therapy with pemetrexed improved PFS in patients with advanced nonsquamous non-small cell lung cancer who also received the chemotherapy drug during their initial treatment regimen, according to study results presented here.

The PARAMOUNT trial is the first to demonstrate the concept of continuation maintenance therapy in patients with nonsquamous NSCLC.

“Pemetrexed has shown to be an effective maintenance treatment in patients who have not received induction treatments,” said lead author Luis, Paz-Ares, MD, PhD, chair of oncology at Seville University Hospital in Seville, Spain. “In this trial, we explored maintenance treatment with pemexetred in patients already treated with pemexetred in the induction phase.”

The double blind, placebo-controlled phase 3 trial included 939 patients who received standard first-line induction therapy of four cycles of 500 mg/m² pemetrexed (Almita, Lilly) and 75 mg/m² cisplatin on the first day of a 21-day cycle. Median patient age was 61 years, and all patients received vitamin B₁₂, folic acid and dexamethasone. Of 539 patients who did not progress on the regimen, 359 received maintenance pemetrexed (500 mg/m² on day 1 of a 21-day cycle) and 180 received placebo and best supportive care. The primary endpoint was PFS.

Continuation maintenance therapy resulted in a significant 38% reduction in the risk of disease progression (HR=0.62; P=0.00025.).

“The hazard ratio of .62 means that patients treated with pemetrexed had a decrease in the risk of progression of 38% in the whole period of the study. The magnitude of the benefit is clinically significant and may support its use in this clinical context.”

Median PFS was 4.1 months in the pemetrexed group and 2.8 months in the placebo group. The disease control rate was 71.8% in the pemetrexed group compared with 59.6% for those receiving placebo.

The most severe grade 3/4 adverse events in the pemetrexed group were fatigue (4.2%), anemia (4.5%) and neutropenia (3.6%). – by Carey Cowles

For more information:

Paz-Ares LG. #CRA7510. Presented at: 2011 ASCO Annual Meeting; Chicago; June 3-7, 2011.

Disclosure: Dr. Paz-Ares has served in a consultant or advisory role for Lilly.

This trial gives the medical oncologist a very important piece of information. A couple of years ago, it was shown that giving pemetrexed with cisplatin as initial therapy for stage IV NSCLC led to a survival improvement over a comparator, gemcitabine, and that was the basis for its use a standard therapy. Approximately 2 years ago another clinical trial was done, where pemetrexed was given not as initial therapy, but as second therapy. There it showed that patients improved their time free of cancer.

One missing piece of information is what do you do about those patients who started pemetrexed, who are doing well on pemetrexed — should you continue it? Would you get the same magnitude of benefit if you switched to something else? Or should you switch to something else? This trial answer that. It’s very important as an example of how you can achieve an incremental benefit in our patients by the optimal use of drugs that are already available. We can improve the lives of these patients in their time free of cancer by extending the time that pemetrexed is given, while we continue to look for other cures.

- Mark G. Kris, MD,
Memorial Sloan-Kettering Cancer Center, New York, NY

Disclosure: Dr. Kris has served in a consultant or advisory role with GlaxoSmithKline, Merck, and Sanofi-Aventis.

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