FROM THE JOURNAL OF CLINICAL ONCOLOGY

A combination of the antifolate agent pemetrexed plus cisplatin with thoracic radiation followed by consolidation with pemetrexed was no better than standard etoposide-cisplatin chemoradiotherapy and platinum doublet consolidation in patients with unresectable stage III nonsquamous, non–small cell lung cancer, results of a randomized clinical trial indicate.

In the PROCLAIM trial, results of which were reported at the American Society of Clinical Oncology’s 2015 annual meeting, there was no significant difference in overall survival between patients randomized to receive pemetrexed-cisplatin or etoposide-cisplatin, leading to early discontinuation of the trial because it had met the prespecified definition of futility, reported Dr. Suresh Senan from the Vrije University Medical Center in Amsterdam and colleagues.

They noted, however, that pemetrexed-cisplatin was less toxic than the current platinum doublet standard.

“A significantly lower incidence of drug-related grade 3 to 4 [adverse events], including neutropenia, was observed during the overall study period for pemetrexed-cisplatin. Grade 3 to 4 neutropenia and febrile neutropenia were also lower for pemetrexed-cisplatin during concurrent therapy. The PROCLAIM trial showed that pemetrexed-cisplatin has an acceptable safety profile, in a scenario in which concurrent chemoradiation remains the standard of care,” the investigators reported in the Journal of Clinical Oncology.

Investigators in the multicenter international trial chose to compare pemetrexed in combination with cisplatin because the antifolate has selective activity against nonsquamous NSCLC and is known to be a radiosensitizer. Additionally, maintenance pemetrexed has been shown in at least two randomized trials to offer a survival advantage following first-line therapy, they noted (J Clin Onc. 2016 Jan 25. doi: 10.1200/JCO.2015.64.8824 ).

In the PROCLAIM trial, patients with stage IIIA or IIIB unresectable nonsquamous NSCLC were randomly assigned to receive either pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks for three cycles with concurrent thoracic radiation at doses of 60 to 66 Gy, followed by pemetrexed consolidation every 3 weeks for four cycles, or to standard therapy with etoposide 50 mg/m2 and cisplatin 50 mg/m2 intravenously every 4 weeks for two cycles with concurrent thoracic radiation at the same doses, followed by two cycles of consolidation with platinum-based doublet chemotherapy.

The trial was designed as a superiority study, with planned enrollment of about 600 patients, with 80% power to detect a hazard ratio of 0.74 for the experimental arm. The trial was stopped early for futility after an interim analysis was performed. At that time, 173 of 552 randomized patients had died.

Median overall survival was 26.8 months for the pemetrexed group vs. 25 months for the standard therapy group (HR, 0.98; P = .831).

tor@frontlinemedcom.com

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