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

C.M.J. Steendam, R. Peric, N.C. van Walree, M. Youssef, F.M.N.H. Schramel, P. Brocken, J.W.G. van Putten, V. van der Noort, G.D.M. Veerman, S.L.W. Koolen, H.J.M. Groen, A.M.C. Dingemans, R.H.J. Mathijssen, E.F. Smit, J.G.J.V. Aerts*, NVALT Study Group

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Web of Science)


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.
Original languageEnglish
Pages (from-to)44-49
Number of pages6
JournalLung Cancer
Publication statusPublished - 1 Oct 2021


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

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