Article Text

Download PDFPDF

33 Olaparib monotherapy versus (VS) chemotherapy for germline BRCA-mutated (GBRCAM) platinum-sensitive relapsed ovarian cancer (PSR OC) patients (PTS): phase III solo3 trial
  1. RT Penson1,
  2. RV Valencia2,
  3. D Cibula3,
  4. N Colombo4,
  5. CL III5,
  6. M Bidzinski6,
  7. JW Kim7,
  8. JH Nam8,
  9. R Madry9,
  10. CH Hernández10,
  11. P Mora11,
  12. SY Ryu12,
  13. T Milenkova13,
  14. e Lowe14,
  15. L Barker13 and
  16. G Scambia15
  1. 1Massachusetts General Hospital, Boston, MA, USA
  2. 2Centro Medico Dalinde, Mexico City, Mexico
  3. 3First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic
  4. 4European Institute of Oncology, Milan, Italy
  5. 5University of Alabama, Birmingham, AL, USA
  6. 6Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland
  7. 7Seoul National University Hospital, Seoul, South Korea
  8. 8Asan Medical Center, Seoul, South Korea
  9. 9Uniwersytet Medyczny im. K. Marcinkowskiego w Poznaniu and Szpital Kliniczny Przemienienia Pańskiego, Poznań, Poland
  10. 10Oaxaca Site Management Organization, Oaxaca de Juarez, Mexico
  11. 11Instituto COI de Educação e Pesquisa, Rio de Janeiro, Brazil
  12. 12Korea Institute of Radiological and Medical Sciences, Seoul, South Korea
  13. 13AstraZeneca, Cambridge, UK
  14. 14AstraZeneca, Gaithersburg, MD, USA
  15. 15Università Cattolica del Sacro Curoe-Fondazione Policlinico A. Gemelli, IRCCS, Rome, Italy


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/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 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.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.