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

Autor: Robert Peric, Vincent van der Noort, Harry J.M. Groen, Anne-Marie C. Dingemans, Nico van Walree, Franz M.N.H. Schramel, Christi M.J. Steendam, Pepijn Brocken, Stijn L.W. Koolen, G.D. Marijn Veerman, John W. G. van Putten, Ron H.J. Mathijssen, Egbert F. Smit, Joachim G.J.V. Aerts, Magdolen Youssef
Přispěvatelé: Pulmonary Medicine, Medical Oncology, Pharmacy, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Pulmonary and Respiratory Medicine
Erlotinib Hydrochloride/therapeutic use
Cancer Research
medicine.medical_specialty
Lung Neoplasms
Combination therapy
Carcinoma
Non-Small-Cell Lung/drug therapy
Quinazolines/therapeutic use
Taxoids/therapeutic use
EGFR
Non-Small-Cell Lung/drug therapy
Docetaxel
Gastroenterology
Disease-Free Survival
Erlotinib Hydrochloride
SDG 3 - Good Health and Well-being
Internal medicine
Carcinoma
Non-Small-Cell Lung
Antineoplastic Combined Chemotherapy Protocols
medicine
Carcinoma
Humans
Progression-free survival
Epidermal growth factor receptor
CANCER PATIENTS
Lung Neoplasms/drug therapy
COMBINATION
neoplasms
SCHEDULE
Docetaxel/therapeutic use
biology
PLASMA
business.industry
Antineoplastic Combined Chemotherapy Protocols/adverse effects
Hazard ratio
CHEMOTHERAPY
medicine.disease
Oncology
Erlotinib
Toxicity
biology.protein
Quinazolines
Taxoids
business
Non-small-cell lung cancer
medicine.drug
Zdroj: Lung Cancer, 160, 44-49. Elsevier Ireland Ltd
Lung Cancer, 160, 44-49. ELSEVIER IRELAND LTD
ISSN: 1872-8332
0169-5002
DOI: 10.1016/j.lungcan.2021.08.002
Popis: 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.
Databáze: OpenAIRE
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