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June 13, 2019

Immune Checkpoint and Poly(ADP–Ribose) Polymerase Inhibition for Recurrent Platinum-Resistant Ovarian and Metastatic Triple-Negative Breast Cancers

Author Affiliations
  • 1Department of Gynecologic Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, New York
  • 2Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, New York
  • 3Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, New York
  • 4Division of Gynecologic Oncology, Department of Obstetrics & Gynecology, Knight Cancer Institute, Oregon Health & Science University, Portland
JAMA Oncol. 2019;5(8):1103-1105. doi:10.1001/jamaoncol.2019.1009

Patients with recurrent platinum-resistant ovarian carcinoma (PROC) or metastatic triple-negative breast cancer (TNBC) have a poor prognosis, and effective management remains a large unmet medical need. Recent advances in multiomic analyses of cancers have uncovered molecular similarities between these 2 clinically distinct entities. In particular, The Cancer Genome Atlas Research Network revealed marked genomic similarities between TNBC and the most frequent ovarian cancer subtype, high-grade serous ovarian carcinoma. Both subtypes exhibit a very high frequency of TP53 (OMIM 191170) mutations, BRCA1 (OMIM 113705) and BRCA2 (OMIM 600185) inactivation, and copy number gains and losses.1 These molecular features suggest that similar biological mechanisms drive some aspects of both cancer types, which in turn may direct their treatment strategies. In addition, high-grade serous ovarian carcinoma and TNBC are potentially immunoreactive tumors, based on observations indicating that the presence of intraepithelial tumor-infiltrating lymphocytes is associated with improved clinical outcomes.2,3 Although no immune checkpoint inhibitor (ICI) has been approved by the US Food and Drug Administration for the treatment of patients with ovarian cancer, 3 poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitors are currently approved as monotherapy in patients with germline or somatic BRCA1/2 mutations, or as maintenance therapy.4 For TNBC, olaparib and talazoparib tosylate are approved PARP inihibitors,5,6 and atezoluzimab is an approved ICI to be used in combination with albumin-bound paclitaxel.7 The TOPACIO (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer)/KEYNOTE-162 clinical trial tested the hypothesis that the combination of a PARP inhibitor, niraparib, with an ICI, pembrolizumab, would be a safe and effective therapy for patients with PROC and TNBC,8,9 and the results are reported in this issue of JAMA Oncology. The first question to ask is what is the scientific premise for this hypothesis?

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