PROCLAIM Trial: Safety Benefit with Pemetrexed Regimen in NSQ NSCLC

PROCLAIM Trial: Safety Benefit with Pemetrexed Regimen in NSQ NSCLC

Dr. Suresh Senan
In patients with advanced nonsquamous non–small cell lung cancer (NSQ NSCLC), a chemotherapy regimen including pemetrexed had a better safety profile than one including etoposide, according to the final results of the phase III PROCLAIM trial (Abstract 7506). The pemetrexed arm did not, however, demonstrate improved overall survival (OS) compared with the control arm, said Suresh Senan, PhD, MRCP, FRCR, of VU University Medical Center, the Netherlands, who presented the results during the Lung Cancer Oral Abstract Session on Saturday, May 30.

Pemetrexed is a multitargeted antifolate with selective activity in NSQ NSCLC. The international, multicenter, randomized PROCLAIM study evaluated the safety and efficacy of two chemoradiotherapy regimens in previously untreated patients with stage IIIA or IIIB NSQ NSCLC. Patients were randomly assigned to concurrent pemetrexed/cisplatin and thoracic radiation therapy (TRT), followed by consolidation pemetrexed, or to etoposide/cisplatin and TRT followed by investigator’s choice among three consolidation chemotherapy regimens.

The primary endpoint was OS, and secondary endpoints included progression-free survival (PFS), objective response rate (ORR; complete response plus partial response), and incidence of adverse events. The trial was powered as a superiority study. Enrollment of 600 patients was planned, for a minimum of 355 deaths with 80% power to detect a hazard ratio (HR) of 0.74 with a two-sided a level of 0.05.

An independent data-monitoring committee evaluated safety data, and a futility analysis was conducted after 165 deaths. The study was stopped after the futility analysis in August 2012, with 598 of the planned 600 patients enrolled.

A total of 555 patients were treated: 283 in the pemetrexed arm and 272 in the etoposide arm. Consolidation was completed in 229 patients in the pemetrexed arm and 202 in the etoposide arm. Baseline characteristics were balanced between arms.

Median OS was 26.8 months in the pemetrexed arm and 25.0 months in the etoposide arm (HR 0.98, 95% CI [0.79, 1.20]; p = 0.831). Median PFS was 11.4 months in the pemetrexed arm and 9.8 months in the etoposide arm (HR 0.86, 95% CI [0.71, 1.04]; p = 0.130). ORR for the pemetrexed arm was 35.9% compared with 33.0% for the etoposide arm (p = 0.458). Disease control rate for the pemetrexed arm was 80.7% compared with 70.7% for the etoposide arm.

The pemetrexed arm had a signifi-cantly lower incidence of grade 3/4 adverse events deemed to be related to the study treatment (64.0%) compared with the etoposide arm (76.8%; p = 0.001). There were lower incidences of neutropenia and granulocytopenia in the pemetrexed arm (24.4%) compared with the etoposide arm (44.5%; p < 0.001).

The study authors concluded that pemetrexed/cisplatin combined with TRT followed by pemetrexed consolidation is a feasible regimen with an acceptable safety profile.

Discussant Mark A. Socinski, MD, of the University of Pittsburgh Medical Center, acknowledged the acceptable toxicity profile of the pemetrexed regimen, with fewer grade 3-5 adverse events compared with the control arm. However, Dr. Socinski questioned whether routine use of the pemetrexed regimen could be justified, with increased costs but no benefit in survival outcomes. “Given the number of cycles and the acquisition costs, there is clearly a major difference in the ‘financial toxicity’ of the regimens.”  

Watch the session: Visit the ASCO Virtual Meeting website.