By Joanna Lyford, Senior medwireNews Reporter
Combination therapy with pemetrexed and erlotinib significantly improves progression-free survival (PFS) as compared with either drug alone in patients with advanced non-squamous non-small-cell lung cancer (NSCLC), a phase II study has found.
The trial, which was restricted to never-smoking patients who had failed first-line therapy, found that tolerability of the combination regimen was “clinically manageable,” albeit with greater frequency of adverse effects than that seen with monotherapy.
The results are likely to have limited impact on current clinical practice, however, as both pemetrexed and epidermal growth factor receptor (EGFR) inhibitors are increasingly being used as first-line therapy, rather than being saved for second-line.
Jung Shin Lee (University of Ulsan, Seoul, Republic of Korea) and colleagues conducted a multicenter, randomized, open-label study to compare three treatments for NSCLC: erlotinib 150 mg daily; pemetrexed 500 mg/m2 on day 1 of a 21-day cycle; or pemetrexed 500 mg/m2 on day 1 plus erlotinib 150 mg daily on days 2–14.
The study participants were a clinically selected population of never-smokers with non-squamous NSCLC who had failed one prior chemotherapy regimen and had an Eastern Cooperative Oncology Group Performance Status (PS) of 2 or less.
A total of 240 patients were enrolled; 35% were male, 55% were of East Asian ethnicity, and 93% had a PS of 0 or 1.
The trial’s primary efficacy endpoint, PFS, was 7.4 months with pemetrexed–erlotinib versus 3.8 months with erlotinib and 4.4 months with pemetrexed. This translated into a statistically significant difference favoring pemetrexed–erlotinib over both erlotinib (hazard ratio [HR]=0.57) and pemetrexed (HR=0.58).
There was no significant difference between the two single-agent regimens (HR=0.99).
With regard to secondary outcomes, overall survival (OS) did not differ among the groups. Importantly, however, the benefit of combination therapy over the single drugs was seen consistently across subgroups stratified by age, race, gender, PS, and genotype.
The frequency of drug-related grade 3/4 toxicity was significantly greater with pemetrexed–erlotinib (60.0%) than with either pemetrexed (28.9%) or erlotinib (12.0%); the most common events with combination therapy were neutropenia, anemia, rash, and diarrhea.
Writing in the European Journal of Cancer, Lee and co-authors say that their results support further evaluation of the pemetrexed–erlotinib combination as first-line therapy in EGFR-mutant NSCLC, “with the aim of prolonging PFS and OS by overcoming or delaying resistance to EGFR [tyrosine kinase inhibitors].”
“Some of these studies are currently ongoing,” they add.
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