Olaparib versus nonplatinum chemotherapy in patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation (SOLO3): A randomized phase III trial: Journal of Clinical Oncology

R.T. Penson, R.V. Valencia, D. Cibula, N. Colombo, III Leath C.A., M. Bidzinski, J.-W. Kim, J.H. Nam, R. Madry, C. Hernández, P.A.R. Mora, S.Y. Ryu, T. Milenkova, E.S. Lowe, L. Barker, G. Scambia

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE A phase II study (ClinicalTrials.gov identifier: NCT00628251) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician’s choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. Copyright © 2020 American Society of Clinical Oncology. All rights reserved.
Original languageEnglish
Pages (from-to)1164-1174
Number of pages11
JournalJ. Clin. Oncol.
Volume38
Issue number11
DOIs
Publication statusPublished - 2020

Keywords

  • antineoplastic metal complex
  • BRCA1 protein
  • BRCA2 protein
  • doxorubicin
  • gemcitabine
  • olaparib
  • paclitaxel
  • topotecan
  • antineoplastic agent
  • phthalazine derivative
  • piperazine derivative
  • platinum derivative
  • abdominal pain
  • acute myeloid leukemia
  • adult
  • aged
  • alopecia
  • anemia
  • Article
  • asthenia
  • cancer chemotherapy
  • cancer patient
  • cancer recurrence
  • carcinogenesis
  • cardiopulmonary insufficiency
  • constipation
  • controlled study
  • diarrhea
  • drug dose reduction
  • drug safety
  • drug sensitivity
  • drug withdrawal
  • female
  • germline mutation
  • hand foot syndrome
  • human
  • major clinical study
  • mesenteric vein thrombosis
  • monotherapy
  • multicenter study
  • myelodysplastic syndrome
  • nausea
  • neutropenia
  • open study
  • ovary cancer
  • phase 3 clinical trial
  • primary tumor
  • priority journal
  • progression free survival
  • randomized controlled trial
  • sepsis
  • stomatitis
  • subarachnoid hemorrhage
  • thrombocytopenia
  • treatment duration
  • treatment response
  • vomiting
  • clinical trial
  • comparative study
  • genetics
  • middle aged
  • mortality
  • ovary tumor
  • tumor recurrence
  • tumor suppressor gene
  • very elderly
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Female
  • Genes, BRCA1
  • Genes, BRCA2
  • Germ-Line Mutation
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Ovarian Neoplasms
  • Phthalazines
  • Piperazines
  • Platinum Compounds

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