Olaparib monotherapy versus (vs) chemotherapy for germline BRCA-mutated (gBRCAm) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (pts): Phase III SOLO3 trial.

Richard T. Penson Massachusetts General Hospital, Boston, MA info_outline Richard T. Penson, Ricardo Villalobos Valencia, David Cibula, Nicoletta Colombo, Charles A. Leath, Mariusz Bidziński, Jae-Weon Kim, Joo-Hyun Nam, Radoslaw Madry, Carlos Hernández Hernández, Paulo Alexandre Ribeiro Mora, Sang Young Ryu, Tsveta Milenkova, Elizabeth S. Lowe, Laura Barker, Giovanni Scambia

Authors Richard T. Penson Massachusetts General Hospital, Boston, MA info_outline Richard T. Penson, Ricardo Villalobos Valencia, David Cibula, Nicoletta Colombo, Charles A. Leath, Mariusz Bidziński, Jae-Weon Kim, Joo-Hyun Nam, Radoslaw Madry, Carlos Hernández Hernández, Paulo Alexandre Ribeiro Mora, Sang Young Ryu, Tsveta Milenkova, Elizabeth S. Lowe, Laura Barker, Giovanni Scambia Organizations Massachusetts General Hospital, Boston, MA, Centro Medico Dalinde, Mexico City, Mexico, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic, European Institute of Oncology, Milan, Italy, University of Alabama, Birmingham, AL, Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland, Seoul National University Hospital, Seoul, South Korea, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea, Uniwersytet Medyczny im K Marcinkowskiego w Poznaniu and Szpital Kliniczny Przemienienia Pańskiego, Poznań, Poland, Oaxaca Site Management Organization, Oaxaca De Juarez, Mexico, Instituto COI de Educação e Pesquisa, Rio De Janeiro, Brazil, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea, AstraZeneca, Cambridge, United Kingdom, AstraZeneca, Gaithersburg, MD, Università Cattolica del Sacro Cuore, Fondazione Policlinico Agostino Gemelli, IRCCS, Rome, Italy Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m 2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m 2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m 2 D1, D8, D15 q4w] or PLD [50 mg/m 2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P =0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P =0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P <0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020