Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma

Steendam, C.M.J.; Peric, R.; Walree, N.C. van; Youssef, M.; Schramel, F.M.N.H.; Brocken, P.; ... ; NVALT Study Grp (2021)

Article / Letter to editor

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/m(2) intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m(2) intravenously on day 1 plus erlotinib 150 mg/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). Corresponding median 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 with combination 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, and strongly discourages further exploration of this combination in clinical practice.

• Non-small-cell lung cancer
• Docetaxel
• Erlotinib

• All authors: Steendam, C.M.J.; Peric, R.; Walree, N.C. van; Youssef, M.; Schramel, F.M.N.H.; Brocken, P.; Putten, J.W.G. van; Noort, V. van der; Veerman, G.D.M.; Koolen, S.L.W.; Groen, H.J.M.; Dingemans, A.M.C.; Mathijssen, R.H.J.; Smit, E.F.; Aerts, J.G.J.V.; NVALT Study Grp
• Date: 2021-10-01
• Journal: Lung Cancer
• Volume: 160
• Pages: 44 - 49
• DOI: doi:10.1016/j.lungcan.2021.08.002
• Link: http://www.lungcancerjournal.info/article/S016950022100489X/pdf