Rosario Garcia-Campelo1, Oscar Arrieta2, Bartomeu Massuti3, Delvys Rodriguez-Abreu4, Ana Laura Ortega Granados5, Margarita Majem6, David Vicente7, Pilar Lianes8, Joaquim Bosch-Barrera9, Amelia Insa10, Manuel Dómine11, Noemí Reguart12, María Guirado13, María Ángeles Sala14, Sergio Vázquez-Estevez15, Reyes Bernabé Caro16, Ana Drozdowskyj17, Ana Verdú18, Niki Karachaliou19, Miguel Angel Molina-Vila19, Rafael Rosell20. 1. University Hospital A Coruña (XXIAC-SERGAS), A Coruña, Spain. 2. Instituto Nacional de Cancerología, Mexico City, Mexico. 3. Alicante University Hospital, Alicante, Spain. 4. Hospital Universitario Insular De Gran Canaria, Las Palmas, Spain. 5. Complejo Hospitalario de Jaén, Jaén, Spain. 6. Hospital de la Santa Creu i Sant Pau, Barcelona, Spain. 7. Hospital Universitario Virgen Macarena, Seville, Spain. 8. Hospital de Mataró, Mataró, Spain. 9. Catalan Institute of Oncology (ICO) and Girona Biomedical Research Institute (IDIBGi), Girona, Spain. 10. Hospital Clínico Universitario de Valencia, Valencia, Spain. 11. Hospital Universitario Fundación Jimenez Diaz, Madrid, Spain. 12. Hospital Clínic Barcelona, Barcelona, Spain; Translational Genomics and Targeted Therapeutics in Solid Tumors, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. 13. Hospital General de Elche, Elche, Alicante, Spain. 14. Hospital Universitario de Basurto, Bilbao, Spain. 15. Hospital Universitario Lucus Augusti, Lugo, Spain. 16. Hospital Virgen Del Rocio, Sevilla, Spain. 17. Germans Trias i Pujol Research Institute and Hospital (IGTP), Badalona, Spain. 18. Spanish Lung Cancer Group Office, Barcelona, Spain. 19. Laboratory of Oncology/Pangaea Oncology, Quiron Dexeus University Hospital, Barcelona, Spain. 20. Germans Trias i Pujol Research Institute and Hospital (IGTP), Badalona, Spain. Electronic address: rrosell@iconcologia.net.
Abstract
OBJECTIVES:Progression-free survival (PFS) and response rate to epidermal growth factor receptor (EGFR) tyrosinekinase 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-naïve, 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 receivedgefitinib 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.
RCT Entities:
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 NSCLCpatients. 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-naïve, 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.
Authors: Antao Chang; Liang Liu; Justin M Ashby; Dan Wu; Yanan Chen; Stacey S O'Neill; Shan Huang; Juan Wang; Guanwen Wang; Dongmei Cheng; Xiaoming Tan; W J Petty; Boris C Pasche; Rong Xiang; Wei Zhang; Peiqing Sun Journal: Cancer Res Date: 2021-04-14 Impact factor: 12.701
Authors: Niki Karachaliou; Oscar Arrieta; Ana Giménez-Capitán; Erika Aldeguer; Ana Drozdowskyj; Imane Chaib; Noemí Reguart; Rosario Garcia-Campelo; Jing-Hua Chen; Miguel Angel Molina-Vila; Rafael Rosell Journal: JTO Clin Res Rep Date: 2020-10-23