@article{09bec0c5d9da4739b89d679124cff5f2,
title = "Randomized phase III study of docetaxel versus docetaxel plus intercalated erlotinib in patients with relapsed non-squamous non-small cell lung carcinoma",
abstract = "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.",
keywords = "Non-small-cell lung cancer, Docetaxel, Erlotinib, CANCER PATIENTS, SCHEDULE, CHEMOTHERAPY, COMBINATION, PLASMA, EGFR",
author = "C.M.J. Steendam and R. Peric and {van Walree}, N.C. and M. Youssef and F.M.N.H. Schramel and P. Brocken and {van Putten}, J.W.G. and {van der Noort}, V. and G.D.M. Veerman and S.L.W. Koolen and H.J.M. Groen and A.M.C. Dingemans and R.H.J. Mathijssen and E.F. Smit and J.G.J.V. Aerts and {NVALT Study Group}",
note = "Funding Information: We thank all patients and their families, and all the colleagues at the participating centers for their contributions to the NVALT-18 trial. This work was supported by The Dutch Cancer Society (Grant number EMCR-2015-8059). The funding source had no involvement in the conduct of the research or the preparation of the article. CS reports advisory board honorarium from Boehringer Ingelheim, grants (to institution) from AstraZeneca, other (hospitality/symposium) from Roche and Lilly, outside the submitted work. SK reports personal fees from Roche, outside the submitted work. HG reports fees (to institution) from Lilly, other from Merck, Novartis, BMS, AbbVie, outside the submitted work. AD reports personal fees from Roche, Eli Lilly, Boehringer Ingelheim, Pfizer, BMS, Novartis, Takeda, Pharmamar, non-financial support from Abbvie, grants from BMS and Amgen, outside the submitted work. RM reports grants from Astellas, Bayer, Boehringer-Ingelheim, Cristal Therapeutics, Pamgene, Pfizer, Prostakan, Roche, grants and personal fees from Novartis and Servier, outside the submitted work. JA reports personal fees and non-financial support from MSD, personal fees from BMS, Boehringer Ingelheim, Amphera, Eli-Lilly, Takeda, Bayer, Roche and AstraZeneca, outside the submitted work. In addition, JA has a patent allogenic tumor cell lysate licensed to Amphera, a patent combination immunotherapy in cancer pending, and a patent biomarker for immunotherapy pending. All remaining authors have declared no conflicts of interest. Funding Information: CS reports advisory board honorarium from Boehringer Ingelheim, grants (to institution) from AstraZeneca, other (hospitality/symposium) from Roche and Lilly, outside the submitted work. SK reports personal fees from Roche, outside the submitted work. HG reports fees (to institution) from Lilly, other from Merck, Novartis, BMS, AbbVie, outside the submitted work. AD reports personal fees from Roche, Eli Lilly, Boehringer Ingelheim, Pfizer, BMS, Novartis, Takeda, Pharmamar, non-financial support from Abbvie, grants from BMS and Amgen, outside the submitted work. Funding Information: This work was supported by The Dutch Cancer Society (Grant number EMCR-2015-8059). The funding source had no involvement in the conduct of the research or the preparation of the article. Publisher Copyright: {\textcopyright} 2021 The Authors",
year = "2021",
month = oct,
day = "1",
doi = "10.1016/j.lungcan.2021.08.002",
language = "English",
volume = "160",
pages = "44--49",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
}