Efficacy of maintenance olaparib for newly diagnosed, advanced ovarian cancer patients (pts) by BRCA1 or BRCA2 mutation in the phase III SOLO1 trial.

person Michael Friedlander Prince of Wales Clinical School, University of New South Wales, and Royal Hospital for Women, Sydney, Australia info_outline Michael Friedlander, Kathleen N. Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, 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, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro

Authors person Michael Friedlander Prince of Wales Clinical School, University of New South Wales, and Royal Hospital for Women, Sydney, Australia info_outline Michael Friedlander, Kathleen N. Moore, Nicoletta Colombo, Giovanni Scambia, Byoung-Gie Kim, Ana Oaknin, 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, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro Organizations Prince of Wales Clinical School, University of New South Wales, and Royal Hospital for Women, Sydney, Australia, Stephenson Oklahoma Cancer Center, Oklahoma City, OK, University of Milan-Bicocca and Istituto Europeo di Oncologia, Milan, Italy, Fondazione Policlinico Universitario A Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, 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, 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 resulted in a significant improvement in progression-free survival (PFS) for newly diagnosed, BRCA1- and/or BRCA2 -mutated, advanced ovarian cancer pts compared with placebo (HR 0.30, 95% CI 0.23–0.41; median not reached vs 13.8 months; Moore et al . N Engl J Med 2018). We investigated PFS in SOLO1 for the subgroups of pts with BRCA1 mutations ( BRCA1 m) or BRCA2 mutations ( BRCA2 m). Methods: All pts were in clinical complete or partial response to platinum-based chemotherapy and were randomized to maintenance olaparib (300 mg twice daily; tablets) or placebo. After 2 years, pts with no evidence of disease discontinued study treatment, but pts with evidence of disease could continue study treatment. PFS by BRCAm was a predefined analysis. BRCAm were identified by central germline (Myriad or BGI) or local testing; Foundation Medicine testing confirmed tumor BRCAm. Results: Median follow-up for PFS was ~41 months in the olaparib and placebo arms. Of 391 randomized pts, 282 had BRCA1 m (72%), 106 had BRCA2 m (27%) and three (1%) had both (Table). Two pts in the olaparib arm had somatic BRCAm (one BRCA1 m, one BRCA2 m); all others had germline BRCAm. At the primary data cut-off, 155 pts in the BRCA1- mutated group (55%), 43 in the BRCA2- mutated group (41%) and none in the BRCA1/2 - mutated group had disease progression. The percentage of BRCA1- mutated pts who received olaparib and were progression-free at 1, 2 and 3 years was 86%, 69% and 53% (vs 52%, 36% and 26% receiving placebo) and for BRCA2- mutated pts was 92%, 85% and 80% (vs 50%, 32% and 29%, respectively). Conclusions: Significant PFS benefit with olaparib versus placebo was demonstrated for all pts, regardless of whether they had BRCA1 m or BRCA2 m. Statistical tests were not used to compare BRCA1- and BRCA2- mutated pts, but those with BRCA2 m appeared to receive greater benefit from maintenance olaparib than those with BRCA1 m. Clinical trial information: NCT01844986 PFS by BRCA1 m and/or BRCA2 m. BRCA1 m BRCA2 m BRCA1/2m Olaparib n=191 Placebo n=91 Olaparib n=66 Placebo n=40 Olaparib n=3 Placebo n=0 Median PFS, months 41.4 13.8 NR 13.8 NR – HR (95% CI) 0.41 (0.30–0.56) 0.20 (0.10–0.37) NC NC, not calculable; NR, not reached