No Survival Benefit of Pemetrexed/Cisplatin Chemoradiation vs Standard Treatment in Nonresectable Stage III NSCLC


Key Points

  • No survival benefit was observed with pemetrexed/cisplatin chemoradiation and pemetrexed consolidation vs standard treatment in patients with nonresectable stage III non–small cell lung cancer.
  • Overall survival was 76% vs 77% at 1 year, 52% vs 52% at 2 years, and 40% vs 37% at 3 years, respectively.

As reported by Senan et al in the Journal of Clinical Oncology, the phase III PROCLAIM trial showed no significant improvement in overall survival for chemoradiation with pemetrexed (Alimta)/cisplatin vs etoposide/cisplatin followed by consolidation pemetrexed vs a platinum-based doublet in patients with nonresectable stage III non–small cell lung cancer (NSCLC).

Study Details

In the open-label trial, 589 patients from 125 sites in 21 countries were randomly assigned to receive pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 every 3 weeks for three cycles plus concurrent thoracic radiation therapy at 60 to 66 Gy followed by pemetrexed consolidation every 3 weeks for four cycles (n = 301) or standard therapy with etoposide at 50 mg/m2 and cisplatin at 50 mg/m2 every 4 weeks for two cycles plus concurrent radiotherapy at 60 to 66 Gy followed by two cycles of consolidation platinum-based doublet chemotherapy (n = 297). Study consolidation therapy was received by 297 and 272 patients, respectively. The primary endpoint was overall survival; the study had 80% power to detect a hazard ratio (HR) of 0.74 with a type 1 error of .05.

Patients in the pemetrexed and standard therapy groups had a median age of 60 and 59 years, 59% and 60% were male, 72% and 69% were white and 18% and 23% were East Asian, and 54% and 51% had stage IIIB disease, respectively.

Overall Survival

Enrollment was stopped early due to futility. Median overall survival was 26.8 months in the pemetrexed group vs 25.0 months in the standard therapy group (HR = 0.98, P = .831). Overall survival was 76% vs 77% at 1 year, 52% vs 52% at 2 years, and 40% vs 37% at 3 years. Median progression-free survival was 11.4 vs 9.8 months (HR = 0.86, P = .130).

Adverse Events

Patients in the pemetrexed group had a lower incidence of drug-related grade 3 or 4 adverse events (64% vs 77%, P = .001), including neutropenia (24% vs 45%, P < .001). Pneumonitis of any grade was more common in the pemetrexed group (17% vs 11%, P  = .37; grade 2 in 11% vs 6%, P = .021).

The investigators concluded: “Pemetrexed-cisplatin combined with [thoracic radiation therapy] followed by consolidation pemetrexed was not superior to standard chemoradiotherapy for stage III unresectable nonsquamous non–small-cell lung cancer.”

The study was supported by Eli Lilly.

Suresh Senan, MRCP, PhD, of Vrije Universiteit Medical Center Amsterdam, is the corresponding author of the Journal of Clinical Oncology article.

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