Olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (C-PATROL): Analysis by BRCA mutation status from a real-world study

BackgroundMaintenance monotherapy with the poly (ADP-ribose) polymerase inhibitor (PARPi) olaparib has demonstrated significant improvements in median progression-free survival (PFS) compared with placebo in patients with platinum-sensitive relapsed ovarian cancer (PSROC) who are in response to platinum-based chemotherapy (PBC). Patients with a BRCA mutation seem to have the greatest likelihood of benefiting from PARPi treatment. We investigated within the C-PATROL study the effect of the BRCA1 vs BRCA2 mutation on clinical outcomes.MethodsThe prospective German non-interventional study C-PATROL (NCT02503436) captured routine clinical data of patients with BRCA1/2-mutated PSROC treated with PBC and receiving olaparib maintenance monotherapy according to label. This predefined subgroup analysis compares patients according to BRCA1 and BRCA2 mutation status. Data were analyzed by descriptive statistics.ResultsBetween 10/2015 and 10/2019, 277 patients were enrolled. Within the ITT set (study selection criteria fulfilled; N=267), 66% vs 31% vs 3% had a mutation in BRCA1, BRCA2, or both, respectively. In the BRCA1 vs BRCA2 subgroup, median age was 59 vs 65.5 years; 93% vs 94% had an ECOG performance status of ≤ 1; and 31% vs 35% had ≥ 2 relapses. Median follow-up was 22 (range: 0–79) vs 37 months (0–80) and median olaparib treatment duration was 13 (0–80) vs 19 months (0–81). Median progression-free survival (PFS) was 12.8 (95% CI 10.7–15.7) vs 28.8 months (15.2–45.0). Median overall survival (OS) was 30.0 (26.5–36.2) vs 72.3 months (53.4–not reached). Adverse events (AEs) were consistent with the known tolerability profile of olaparib. Serious AEs were reported in 53 (29%) vs 18 (22%) patients. The most frequently reported AE grade ≥ 3 was anemia (17% vs 10%). Olaparib was discontinued due to AEs in 11% of patients (BRCA1 and BRCA2).ConclusionsData observed in this real-word study are comparable to existing studies and supports efficacy and tolerability of olaparib maintenance therapy after PBC in patients with BRCAm PSROC1-4. Potential prognostic differences according to BRCA1 and BRCA2 mutation status may require further attention.Clinical trial identificationNCT02503436.Editorial acknowledgementMedical writing assistance provided by Dr. Yvonne Holighaus, Alcedis GmbH, Giessen, also funded by AstraZeneca.Legal entity responsible for the studyThis study is funded by AstraZeneca and is part of an alliance between AstraZeneca and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.FundingAstraZeneca.DisclosureJ. Sehouli: Financial Interests, Personal, Advisory Board: Roche, GSK, AstraZeneca, MSD, Tesaro, ImmunoGen, Tubulis, Novocure, Incyte; Financial Interests, Personal, Invited Speaker: Eisei; Financial Interests, Institutional, Funding: Roche, GSK, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Novocure; Non-Financial Interests, Institutional, Proprietary Information: ENGOT/NOGGO; Non-Financial Interests, Leadership Role, Council Member: ESGO; Non-Financial Interests, Leadership Role: North-Eastern German Society of Gynecological Oncology (NOGGO), Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO), Pab-Arabian Research Society of Gynecological Oncology (PARSGO). F. Hilpert: Financial Interests, Personal, Advisory Board: MSD, ImmunoGen; Financial Interests, Personal, Invited Speaker: MSD, GSK, AstraZeneca, Novartis. M.K. Welslau: Financial Interests, Advisory Board: Amgen, Bristol Myers Squibb, Celgene, Gilead, Hexal, Janssen, Lilly, Medac, Novartis, Roche, Sanofi; Financial Interests, Other, Honoraria: Amgen, Astellas, AstraZeneca, Celgen, Gilead, Hexal, Janssen, Lilly, Novartis, Roche, Sanofi. J.P. Grabowski: Financial Interests, Advisory Board: AstraZeneca, GSK, MSD, Esteve; Financial Interests, Speaker’s Bureau: AstraZeneca, MSD, GSK, Eisai, Esteve; Financial Interests, Research Funding: AstraZeneca, GSK, MSD, Esteve; Financial Interests, Invited Speaker: AstraZeneca, GSK, MSD, Eisai, Esteve; Financial Interests, Other, Travel Expenses: AstraZeneca, GSK, Eisai; Financial Interests, Other, Travel expenses: MSD. A. Schneeweiss: Financial Interests, Research Grant: Celgene, Roche, AbbVie; Financial Interests, Other, Travel expenses: Celgene, Roche, AstraZeneca; Financial Interests, Other, Honoraria: Roche, Celgene, Pfizer, AstraZeneca, Novartis, MSD, Tesaro, Lilly, Seagen, Gilead, GSK, Bayer, Amgen, Pierre Fabre; Financial Interests, Other, Travel Expenses: Pfizer. A.D. Hartkopf: Financial Interests, Advisory Board: Roche, Novartis, MSD, AstraZeneca, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline, Pfizer; Financial Interests, Other, Honoraria: Roche, Novartis, Lilly, MSD, AstraZeneca, Seagen, GSK, ExactScience, Riemser, Teva, Onkowissen, Gilead, Menarini Stemline; Financial Interests, Other, Travel expenses: Roche, Novartis, Lilly, AstraZeneca, GSK, ExactScience, Gilead, Menarini Stemline, Pfizer, Daichii Sankyo. S. Becker: Financial Interests, Invited Speaker: Roche, Novartis, AstraZeneca, MSD, Pfizer. D. Bauerschlag: Financial Interests, Advisory Board: AstraZeneca, Eisai, MSD, Roche, Novartis; Financial Interests, Speaker’s Bureau: AstraZeneca; Financial Interests, Other, Honoraria: AstraZeneca, Eisai, MSD, Roche, Novartis; Financial Interests, Other, travel, accommodations, expenses: AstraZeneca, Eisai, MSD, Roche, Novartis. P.A. Fasching: Financial Interests, Personal, Advisory Board: Roche, Novartis, Pfizer, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Hexal, Lilly, Pierre Fabre, Seagen, Agendia, Sanofi Aventis, Medac, Menarini, Veracyte; Financial Interests, Personal, Invited Speaker: Novartis, Daiichi Sankyo, Eisai, Merck, Sharp & Dohme, AstraZeneca, Lilly, Seagen, Gilead, Mylan; Financial Interests, Personal, Other, Medical Writing Support: Roche; Financial Interests, Institutional, Local PI: BionTech, Cepheid; Non-Financial Interests, Member: ASCO, Arbeitsgemeinschaft für Gynäkologische Onkologie e.V., Translational Research in Oncology, Deutsche Gesellschaft für Senologie e.v.. R.M. Glowik: Financial Interests, Full or part-time Employment: AstraZeneca. F. Marmé: Financial Interests, Personal, Invited Speaker: AstraZeneca, GSK/Tesaro, Clovis, Pfizer, Lilly; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD, Novartis, Roche, Gilead/Immunomedics, Eisai, PharmaMar, GenomicHealth, Myriad, Seagen; Financial Interests, Institutional, Invited Speaker: Seagen, Daiichi Sankyo, GSK, AstraZeneca, Stemline Menarini; Financial Interests, Institutional, Advisory Board: Roche, Immunicom; Financial Interests, Institutional, Local PI: Roche, Novartis, Eisai, MSD, Vaccibody, GSK; Financial Interests, Institutional, Coordinating PI: AstraZeneca, Roche, Gilead/Immunomedics, German Breast Group, AGO Research GmbH; Financial Interests, Institutional, Funding: AstraZeneca, Lilly, Seagen. All other authors have declared no conflicts of interest.