Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.

person Nicoletta Colombo University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy info_outline Nicoletta Colombo, Kathleen N. Moore, Giovanni Scambia, Ana Oaknin, Michael Friedlander, Alla Sergeevna Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Susana N. Banerjee, Amit M. Oza, Antonio González-Martín, Carol Aghajanian, William Hampton Bradley, Jae-Weon Kim, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro

Authors person Nicoletta Colombo University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy info_outline Nicoletta Colombo, Kathleen N. Moore, Giovanni Scambia, Ana Oaknin, Michael Friedlander, Alla Sergeevna Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Susana N. Banerjee, Amit M. Oza, Antonio González-Martín, Carol Aghajanian, William Hampton Bradley, Jae-Weon Kim, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro Organizations University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy, Stephenson Cancer Center at the University of Oklahoma, Oklahoma City, OK, Fondazione Policlinico Universitario A. Gemelli IRCCS Università Cattolica, Rome, Italy, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, University of New South Wales Clinical School, Prince of Wales Hospital, Randwick, Australia, St Petersburg City Oncology Dispensary, St Petersburg, Russia, Institut Bergonié, Comprehensive Cancer Centre, Bordeaux, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, Bordeaux, France, Gustave-Roussy Cancer Campus, Villejuif, and Groupe d’Investigateurs Nationaux pour l’Etude des Cancers Ovariens, France, The Netherlands Cancer Institute, Amsterdam, Netherlands, Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom, The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, United Kingdom, Princess Margaret Cancer Centre, Toronto, ON, Canada, MD Anderson Cancer Center, Madrid, Spain, Memorial Sloan Kettering Cancer Center, New York, NY, Froedtert and the Medical College of Wisconsin, Milwaukee, WI, Seoul National University, Seoul, South Korea, AstraZeneca, Gaithersburg, MD, AstraZeneca, Cambridge, United Kingdom, Women & Infants Hospital, Providence, RI Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: In SOLO1 (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit vs placebo in newly diagnosed pts with advanced OC, a BRCAm and clinical complete or partial response to platinum therapy (HR 0.30; 95% CI 0.23–0.41) and was well tolerated (Moore et al. NEJM 2018). We analysed the most common AEs and hematologic AEs in SOLO1. Methods: Pts received olaparib tablets 300 mg twice daily or placebo until progression unless they had no evidence of disease at 2 years, in which case treatment stopped. AEs were graded using CTCAE v4.0. Results: Of 391 pts randomized, 390 (olaparib, 260; placebo, 130) were treated and included in the safety analysis. Median treatment duration was approximately 25 months for olaparib vs 14 for placebo. Median time to first onset of the most common AEs (nausea, vomiting, fatigue/asthenia, anemia) and neutropenia and thrombocytopenia was < 3 months; the first event lasted a median of < 2 months, apart from fatigue/asthenia, which lasted a median of < 4 months (Table). AEs were usually managed with supportive therapy and/or dose modification; few pts discontinued. Conclusions: AEs in newly diagnosed pts with advanced OC treated with olaparib usually occurred early and were manageable, with few discontinuations. Clinical trial information: NCT01844986 Nausea Vomiting Fatigue/ asthenia Anemia* Neutro- penia* Thrombo- cytopenia* O P O P O P O P O P O P Pts with AE, n (%) 201 (77) 49 (38) 104 (40) 19 (15) 165 (63) 54 (42) 101 (39) 13 (10) 60 (23) 15 (12) 29 (11) 5 (4) Median time to first event, months 0.13 0.69 1.46 1.94 0.72 1.54 1.94 1.81 1.77 0.49 2.83 7.39 Median duration of first event, † months 1.41 0.43 0.07 0.03 3.48 2.30 1.87 1.64 0.76 0.49 0.95 0.49 Supportive therapy, n (%) 117 (45) 15 (12) 28 (11) 3 (2) 11 (4) 0 72 (28) 4 (3) 11 (4) 2 (2) 2 (1) 1 (1) Dose interruption, n (%) 35 (13) 0 25 (10) 3 (2) 20 (8) 1 (1) 58 (22) 1 (1) 30 (12) 5 (4) 6 (2) 0 Dose reduction, n (%) 10 (4) 0 0 0 15 (6) 1 (1) 44 (17) 1 (1) 10 (4) 1 (1) 4 (2) 0 Discontinuation, n (%) 6 (2) 1 (1) 2 (1) 0 6 (2) 1 (1) 6 (2) 0 1 ( < 1) 0 1 ( < 1) 0 Grade 3–4 AE, n (%) 2 (1) 0 1 ( < 1) 1 (1) 10 (4) 2 (2) 56 (22) 2 (2) 22 (8) 6 (5) 2 (1) 2 (2) *Grouped term; † AEs with no end date censored at end of safety follow-up or data cut-off, as applicable. O, olaparib; P, placebo