1. Combination of gefitinib and olaparib versus gefitinib alone in EGFR mutant non-small-cell lung cancer (NSCLC): A multicenter, randomized phase II study (GOAL)
- Author
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Margarita Majem, Bartomeu Massuti, Joaquim Bosch-Barrera, Ana Drozdowskyj, Pilar Lianes, Delvys Rodriguez-Abreu, Miguel Angel Molina-Vila, M. Guirado, David Vicente, Sergio Vazquez-Estevez, A. Insa, Niki Karachaliou, Manuel Domine, Rafael Rosell, Rosario García-Campelo, Reyes Bernabe Caro, Oscar Arrieta, María Ángeles Sala, Ana Verdu, Ana Laura Ortega Granados, and Noemi Reguart
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,EGFR ,non-small cell lung cancer (NSCLC) ,Phases of clinical research ,Disease-Free Survival ,Piperazines ,Olaparib ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Gefitinib ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Epidermal growth factor receptor ,Lung cancer ,Mexico ,Protein Kinase Inhibitors ,neoplasms ,Performance status ,biology ,business.industry ,medicine.disease ,respiratory tract diseases ,ErbB Receptors ,030104 developmental biology ,Tolerability ,chemistry ,Spain ,030220 oncology & carcinogenesis ,Mutation ,Quinazolines ,biology.protein ,Phthalazines ,business ,Non-small-cell lung cancer ,Goals ,medicine.drug - Abstract
Objectives Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) varies in patients with non-small-cell lung cancer (NSCLC) driven byEGFR mutations, suggesting that other genetic alterations may influence oncogene addiction. Low BRCA1 mRNA levels correlate with longer PFS in erlotinib-treated EGFR-mutant NSCLC patients. Since the poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, may attenuate and/or prevent BRCA1 expression, the addition of olaparib to gefitinib could improve outcome in EGFR-mutant advanced NSCLC. Materials and methods GOAL was a multicenter, randomized phase IB/II study performed in two countries, Spain and Mexico. Eligible patients were 18 years or older, treatment-naive, pathologically confirmed stage IV NSCLC, with centrally confirmed EGFR mutations and measurable disease. Patients were randomly allocated (1:1) to receive gefitinib 250 mg daily or gefitinib 250 mg daily plus olaparib 200 mg three times daily in 28-day cycles. The primary endpoint was PFS. Secondary endpoints included overall survival (OS), response rate, safety and tolerability. Results Between September 2013, and July 2016, 182 patients underwent randomization, 91 received gefitinib and 91 received gefitinib plus olaparib. There were no differences in gender, age, smoking status, performance status, presence of bone and brain metastases or type ofEGFR mutation. Median PFS was 10.9 months (95 % CI 9.3–13.3) in the gefitinib arm and 12.8 months (95 % CI 9.1–14.7) in the gefitinib plus olaparib arm (HR 1.38, 95 % CI 1.00–1.92; p = 0.124). The most common adverse events were anemia, 78 % in gefitinib plus olaparib group, 38 % in gefitinib arm, diarrhea, 65 % and 60 %, and fatigue, 40 % and 32 %, respectively. Conclusions The gefitinib plus olaparib combination did not provide significant benefit over gefitinib alone. The combination’s safety profile showed an increase in hematological and gastrointestinal toxicity, compared to gefitinib alone, however, no relevant adverse events were noted.
- Published
- 2020