Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma
Mené sur 45 patients atteints d'un carcinome du poumon non à petites cellules non épidermoïde récidivant, cet essai de phase III évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout de l'erlotinib au docétaxel
Background : Earlier preclinical and phase II research showed enhanced effect of docetaxel plus intercalated erlotinib. The NVALT-18 phase III study was designed to compare docetaxel with docetaxel plus intercalated erlotinib in relapsed metastasized non-squamous (NSQ)non-small cell lung cancer (NSCLC). Methods : Patients with relapsed Epidermal Growth Factor Receptor (EGFR) wild type (WT) NSQ-NSCLC were randomized 1:1 to docetaxel 75 mg/m2 intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m2 intravenously on day 1 plus erlotinib 150mg/day orally on day 2-16 every 21 days(experimental arm). Progression free survival (PFS) was the primary endpoint, secondary objectives were duration of response, overall survival (OS) and toxicity. Results : Between October 2016 and April 2018 a total of 45 patients were randomized and received treatment in the control (N =23) or experimental arm (N =22), the study was stopped due to slow accrual. Median PFS was 4.0 months (95% CI:1.5-7.1) versus 1.9 months (95% CI 1.4-3.5), p=0.01 respectively; adjusted hazard ratio (HR) 2.51 (95% CI: 1.16-5.43). Correspondingmedian OS was 10.6 months (95% CI: 7.0-8.6) versus 4.7 months (95% CI: 3.2-8.6), p=0.004, with an adjusted HR of 3.67 (95% CI: 1.46-9.27). Toxicity was higher withcombination therapy, with toxicity ≥ CTCAE grade 3 in N =6 (26%) in the control arm and N =17 (77%) in the experimental arm (p<0.001), mainly consisting of gastrointestinal symptoms and leukopenia. Conclusions : Our study shows detrimental effects of docetaxel plus intercalated erlotinib, and8 strongly discourages further exploration of this combination in clinical practice.