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Comment & Response
December 26, 2019

BRCA Mutations and Homologous Recombination Repair Deficiency in Treatment With Niraparib Combined With Pembrolizumab—Reply

Author Affiliations
  • 1Division of Gynecologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
  • 2Fred Hutchinson Cancer Research Center, Division of Oncology, University of Washington School of Medicine, Seattle Cancer Care Alliance, Seattle
JAMA Oncol. 2020;6(3):441. doi:10.1001/jamaoncol.2019.4601

In Reply We thank Lin and colleagues for their comments and interest in the TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial1,2 of combination niraparib and pembrolizumab treatment in patients with recurrent ovarian cancer or triple-negative breast cancer (TNBC). We would like to address their comment that the objective response rate (ORR) for patients with ovarian cancer was not associated with tumor BRCA (tBRCA) mutation or homologous recombination repair (HRR) deficiency status. Although we expected that patients with tBRCA-mutated ovarian cancer would have better outcomes than patients with tBRCA wild-type mutations given the results from poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor monotherapy,3 intriguingly, we found that the ORR was comparable across all ovarian cancer biomarker subpopulations, with efficacy in patients without tBRCA mutations or HRR deficiency. In the TNBC population, the ORRs were higher in patients with tBRCA mutations as expected; however, the key finding was that responses were still observed in patients without tBRCA mutations. Hence, our overall conclusion was that this combination therapy demonstrated clinical activity irrespective of BRCA mutation. This was not entirely unexpected because preclinical evidence of synergism between PARP and PD-1 (programmed cell death 1) inhibition has been reported in HRR-deficient and HRR-proficient models.4

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