Pamiparib Monotherapy for Patients with Germline BRCA1/2-Mutated Ovarian Cancer Previously Treated with at Least Two Lines of Chemotherapy: A Multicenter, Open-Label, Phase II Study

Clin Cancer Res. 2022 Feb 15;28(4):653-661. doi: 10.1158/1078-0432.CCR-21-1186.

Abstract

Purpose: Phase I results of this phase I/II study showed that pamiparib 60 mg twice a day had antitumor activity and an acceptable safety profile in Chinese patients with advanced cancer, including epithelial ovarian cancer.

Patients and methods: This open-label phase II study was conducted in China and enrolled adult (≥18 years) patients with platinum-sensitive ovarian cancer (PSOC; disease progression occurring ≥6 months after last platinum treatment) or platinum-resistant ovarian cancer (PROC; disease progression occurring <6 months after last platinum treatment). Eligible patients had known or suspected deleterious germline BRCA mutation (gBRCAmut) and had previously received ≥2 lines of therapy. Pamiparib 60 mg orally twice a day was administered until disease progression, toxicity, or patient withdrawal. The primary endpoint was objective response rate (ORR) assessed by independent review committee (IRC) per RECIST version 1.1.

Results: In the total patient population (N = 113; PSOC, n = 90; PROC, n = 23), median age was 54 years (range, 34-79) and 25.6% of patients received ≥4 prior systemic chemotherapy lines. Median study follow-up was 12.2 months (range, 0.2-21.5). Eighty-two patients with PSOC and 19 patients with PROC were evaluable for efficacy. In patients with PSOC, 8 achieved a complete response (CR) and 45 achieved a partial response (PR); ORR was 64.6% [95% confidence interval (CI), 53.3-74.9]. In patients with PROC, 6 achieved a PR; ORR was 31.6% (95% CI, 12.6-56.6). Frequently reported grade ≥3 adverse events were hematologic toxicities, including anemia and decreased neutrophil count.

Conclusions: Pamiparib 60 mg twice a day showed antitumor activity with durable responses in patients with PSOC or PROC with gBRCAmut, and had a manageable safety profile.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BRCA1 Protein / genetics
  • Carcinoma, Ovarian Epithelial / drug therapy
  • Carcinoma, Ovarian Epithelial / genetics
  • Female
  • Fluorenes
  • Germ Cells
  • Humans
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / genetics
  • Ovarian Neoplasms* / pathology
  • Poly(ADP-ribose) Polymerase Inhibitors*

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • Fluorenes
  • Poly(ADP-ribose) Polymerase Inhibitors
  • pamiparib