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Veliparib Monotherapy to Patients With BRCA Germ Line Mutation and Platinum-Resistant or Partially Platinum-Sensitive Relapse of Epithelial Ovarian Cancer: A Phase I/II Study
  1. Karina Dahl Steffensen, MD, PhD*,,
  2. Parvin Adimi, MD* and
  3. Anders Jakobsen, MD, DMSc*,
  1. * Department of Oncology, Vejle Hospital, Vejle;
  2. Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
  1. Address correspondence and reprint requests to Karina Dahl Steffensen, MD, PhD, Department of Oncology, Vejle Hospital, Beriderbakken 4, DK-7100 Vejle, Denmark. E-mail: Karina.Dahl.Steffensen{at}rsyd.dk.

Abstract

Objective A new treatment principle, which seems to radically change the treatment approach in ovarian cancer (OC), has developed over the past few years. Poly(ADP-ribose) polymerase inhibitors work by interfering with mechanisms important to DNA damage repair. Cancer cells that already have defects in the BRCA genes are particularly sensitive to treatment with poly(ADP-ribose) polymerase inhibitors. The main purpose of this study was to investigate the effect of veliparib in patients with known BRCA1/2 mutations and with a platinum-resistant or intermediate sensitive relapse of OC.

Methods Major eligibility criteria were primary epithelial ovarian/fallopian/peritoneal cancer patients with a platinum-resistant or intermediate sensitive relapse of OC and with evaluable disease by either Response Evaluation Criteria In Solid Tumors or Gynecological Cancer Intergroup CA-125 criteria. Patients were treated with oral veliparib twice daily on days 1 to 28.

Results Sixteen patients were enrolled in the phase I part, and a maximum tolerable dose of 300 mg twice daily was established. The phase II part enrolled 32 patients with a median of 4 previous treatment regimens. The overall response rate combining Response Evaluation Criteria In Solid Tumors and CA-125 response was 65% (6% complete response and 59% partial response). Progression-free and overall survival rates of the intention-to-treat population were 5.6 months (95% confidence interval, 5.2–7.3 months) and 13.7 months (95% confidence interval, 10.2–17.3 months), respectively. The most common phase II treatment-related grade 2 toxicities included fatigue (22%), nausea (22%), and vomiting (9%).

Conclusions Treatment with veliparib in heavily pretreated patients with relapse of OC demonstrates a considerable efficacy with an acceptable toxicity profile.

  • BRCA
  • Ovarian cancer
  • PARPi
  • Platinum resistance
  • Synthetic lethality

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Footnotes

  • The authors declare no conflicts of interest.

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