Efficacy and safety of rucaparib maintenance treatment in patients from ARIEL3 with platinum-sensitive, recurrent ovarian carcinoma not associated with homologous recombination deficiency.

Robert L. Coleman U.S. Oncology Research, The Woodlands, TX info_outline Robert L. Coleman, Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew R. Clamp, Giovanni Scambia, Alexandra Leary, Robert W. Holloway, Margarita Amenedo Gancedo, Peter C.C. Fong, Jeffrey C. Goh, David M. O'Malley, Sandra M. Goble, Lara Maloney, Jonathan A. Ledermann

Authors Robert L. Coleman U.S. Oncology Research, The Woodlands, TX info_outline Robert L. Coleman, Amit M. Oza, Domenica Lorusso, Carol Aghajanian, Ana Oaknin, Andrew Dean, Nicoletta Colombo, Johanne I Weberpals, Andrew R. Clamp, Giovanni Scambia, Alexandra Leary, Robert W. Holloway, Margarita Amenedo Gancedo, Peter C.C. Fong, Jeffrey C. Goh, David M. O'Malley, Sandra M. Goble, Lara Maloney, Jonathan A. Ledermann Organizations U.S. Oncology Research, The Woodlands, TX, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Unità di Ginecologia Oncologica, Fondazione IRCCS Istituto Nazionale dei Tumori and MITO, Milan, Italy, Gynecologic Medical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, Gynaecologic Cancer Programme, Vall d’Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Department of Oncology, St John of God Subiaco Hospital, Subiaco, Western Australia, Australia, Gynecologic Cancer Program, European Institute of Oncology and University of Milan-Bicocca, Milan, Italy, Division of Gynecologic Oncology, Ottawa Hospital Research Institute, Ottawa, ON, Canada, Department of Medical Oncology, The Christie NHS Foundation Trust and University of Manchester, Manchester, United Kingdom, Gynecologic Oncology, Policlinico Universitario A. Gemelli IRCCS Università Cattolica del Sacro Cuore Roma, Rome, Italy, Gynecological Unit, Gustave Roussy Cancer Center, INSERM U981; Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO), Villejuif, France, Department of Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando, FL, Medical Oncology Department, Oncology Center of Galicia, La Coruña, Spain, Medical Oncology Department, Auckland City Hospital, Grafton, Auckland, New Zealand, Department of Oncology, Cancer Care Services, Royal Brisbane and Women’s Hospital, Herston, QLD, Australia, and University of Queensland, St. Lucia, QLD, Australia, Clinical Research Gynecologic Oncology, The Ohio State University, James Cancer Center, Columbus, OH, Biostatistics, Clovis Oncology, Inc., Boulder, CO, Clinical Development, Clovis Oncology, Inc., Boulder, CO, Department of Oncology, UCL Cancer Institute, University College London and UCL Hospitals, London, United Kingdom Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: In ARIEL3 (NCT01968213), rucaparib maintenance treatment led to significant improvement vs placebo for the primary endpoint of investigator-assessed progression-free survival (PFS) in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma responsive to the last line of platinum therapy (Coleman et al. Lancet . 2017;390:1949–61). The largest benefit was observed in pts with carcinomas with a BRCA mutation or high loss of heterozygosity (LOH), a marker of homologous recombination deficiency (HRD). However, rucaparib also improved PFS in pts with carcinomas negative by HRD test (ie, BRCA wild-type with low LOH), a subset of pts for which there is no identified molecular mechanism conferring PARP inhibitor sensitivity. Among these pts (rucaparib, n = 107; placebo, n = 54), median PFS was 6.7 vs 5.4 months, respectively (HR, 0.58 [95% CI 0.40–0.85]; P = 0.0049), and 31.8% vs 4.3% were progression-free at 1 yr. In this post hoc exploratory analysis, we further evaluated the efficacy of rucaparib maintenance vs placebo in this subset of pts. Methods: Pts were randomized 2:1 to oral rucaparib (600 mg BID) or placebo. For this analysis, investigator-assessed PFS and safety were evaluated in pts with HRD-negative carcinoma, defined as BRCA wild-type with genomic LOH < 16% using Foundation Medicine’s T5 NGS assay. Results: Visit cutoff dates for efficacy and safety were Apr 15, 2017, and Dec 31, 2019. Across subgroups based on demographic or disease characteristics, the trend of rucaparib benefit vs placebo was consistently observed in pts with HRD-negative carcinoma (Table). The safety profile of rucaparib in the HRD-negative population was consistent with that of the overall safety population reported previously. Conclusions: Rucaparib maintenance reduced risk of progression in pts with ovarian carcinomas, including those not associated with HRD, regardless of clinical prognostic factors. Baseline Characteristic Subcategory HR (95% CI) Subcategory HR (95% CI) Age < 65 years (n = 86) 0.48 (0.25–0.90) ≥65 years (n = 75) 0.56 (0.31–1.03) Race White (n = 128) 0.64 (0.42–0.98) Other/unknown (n = 33) 0.52 (0.22–1.23) Measurable disease at baseline Yes (n = 66) 0.60 (0.32–1.12) No (n = 95) 0.53 (0.31–0.89) Bulky disease at baseline Yes (n = 36) 0.62 (0.25–1.54) No (n = 125) 0.59 (0.39–0.91) Number of prior chemotherapy regimens 2 (n = 112) 0.65 (0.42–1.03) ≥3 (n = 49) 0.48 (0.22–1.06) Previous bevacizumab use Yes (n = 40) 0.60 (0.25–1.45) No (n = 121) 0.57 (0.37–0.88) Number of prior platinum regimens 2 (n = 113) 0.64 (0.41–1.00) ≥3 (n = 48) 0.51 (0.23–1.15) Time to disease progression with penultimate platinum 6–≤12 months (n = 57) 0.44 (0.23–0.85) > 12 months (n = 104) 0.66 (0.42–1.05) Response to last platinum RECIST complete response (n = 56) 0.44 (0.22–0.91) RECIST/CA-125 partial response (n = 105) 0.65 (0.41–1.01)