RCT of first-line TKI versus intercalated TKI with chemotherapy for EGFR mutated NSCLC

IntroductionPrevious studies have shown interference between EGFR TKI and chemotherapy in the cell cycle, thus reducing efficacy. In this RCT we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR mutated NSCLC.Materials and methodsTreatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy (E). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR) and toxicity.ResultsBetween April 2014 to September 2016 twenty-two patients were randomized equally into both arms, the study was stopped due to slow accrual. Median follow up was 64 months. Median PFS was 13.7 months (95%CI 5.2–18.8) for CPE and 10.3 months (95%CI 7.1–15.5, HR 0.62 (95%CI 0.25–1.57)) for E, when compensating for number of days receiving erlotinib, PFS of CPE arm was superior (HR 0.24 (95% CI 0.07–0.83; p=0.02)). ORR was 64% for CPE versus 55% for E. Median OS was 31.7 months (95%CI 21.8–61.9) for CPE compared to 17.2 months (95%CI 11.5–45.5) for E (HR 0.58 (95%CI 0.22–1.41)). Patients treated with CPE had higher rates of treatment related fatigue, anorexia, weight loss and renal toxicity.ConclusionIntercalating erlotinib with cisplatin/pemetrexed provides a longer PFS compared to erlotinib alone in EGFR mutated NSCLC at the expense of more toxicity.