<p>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<sup>2</sup> intravenously on day 1 every 21 days (control), or docetaxel 75 mg/m<sup>2</sup> 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 &lt; 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.</p>

doi.org/10.1016/j.lungcan.2021.08.002, hdl.handle.net/1765/136628
Lung Cancer
Erasmus MC: University Medical Center Rotterdam

C.M.J. (Christi) Steendam, R (Robert) Peric, Nico C. van Walree, Magdolen Youssef, Franz M.N.H. Schramel, P Brocken, … J.G.J.V. (Joachim) Aerts. (2021). Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma. Lung Cancer, 160, 44–49. doi:10.1016/j.lungcan.2021.08.002