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Abstract

Perol et al. performed a randomized Phase III trial for patients with advanced non-smallcell lung cancer (NSCLC) in which two maintenance strategies were investigated: continuation maintenance with gemcitabine or switch maintenance with erlotinib. A total of 464 NSCLC patients who did not progress after four cycles of induction chemotherapy with cisplatin plus gemcitabine were randomly assigned to observation, gemcitabine or erlotinib study arms until disease progression, unacceptable toxicity or death. On disease progression, patients in all three arms received pemetrexed as the predefined second-line therapy. A significant improvement in progression-free survival, the primary end point of the trial, with gemcitabine (3.8 vs 1.9 months; hazard ratio [HR]: 0.56; 95% CI: 0.44–0.72; p < 0.001) and erlotinib (2.9 vs 1.9 months; HR: 0.69; 95% CI: 0.54–0.88; p < 0.003) versus observation alone was observed. This benefit was consistent across all clinical subgroups. Progression-free survival improvement did not translate into a significant overall survival (OS) advantage in both gemcitabine versus observation (median OS: 12.1 vs 10.8 months; HR: 0.89; 95% CI: 0.69–1.15; p = 0.3867) and erlotinib versus observation (median OS: 11.4 vs 10.8 months; HR: 0.87; 95% CI: 0.68–1.13; p = 0.3043). The exploratory subgroup analysis suggested that patients who received second-line pemetrexed or with a performance status of 0 appeared to derive greater benefit in both maintenance arms, while the response to induction chemotherapy may affect the OS benefit as a result of gemcitabine maintenance. Maintenance gemcitabine and erlotinib were well tolerated, with no unexpected adverse events. This is the first study simultaneously exploring both continuous and switch maintenance therapy. This trial confirms that the maintenance strategy significantly improves duration of disease control in patients with advanced NSCLC. The lack of an OS benefit could be related to the standardization of second-line treatment with pemetrexed, which was also administered in all histology subgroups (~35% of patients in the three arms were affected by squamous or unknown NSCLC) because the study was designed and conducted before the labeling restriction of pemetrexed to nonsquamous NSCLC. Ongoing Phase III randomized trials exploring the two maintenance approaches might further help in defining the most appropriate strategy to employ in this setting.