Format

Send to

Choose Destination
JAMA Oncol. 2019 Jun 13. doi: 10.1001/jamaoncol.2019.1048. [Epub ahead of print]

Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma.

Author information

1
Division of Gynecologic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
2
Center for DNA Damage and Repair, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
3
Department of Reproductive Medicine, Case Western Reserve University School of Medicine, University Hospitals of Cleveland, Cleveland, Ohio.
4
Division of Medical Oncology, West Cancer Center, Memphis, Tennessee.
5
Department of Hematology and Oncology, Cedars-Sinai Medical Center, Los Angeles, California.
6
Section of Gynecologic Oncology, Department of Obstetrics & Gynecology, University of Chicago Medicine, Chicago, Illinois.
7
Division of Gynecologic Oncology, Florida Hospital Gynecologic Oncology, Florida Hospital Cancer Institute, Orlando.
8
Global Robotics Institute, Orlando, Florida.
9
Department of Obstetrics & Gynecology, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill.
10
Division of Hematology and Oncology, Virginia G. Piper Cancer Center Clinical Trials, HonorHealth Research Institute, Scottsdale, Arizona.
11
Translational Genomics Research Institute, Scottsdale, Arizona.
12
Weill Cornell Medicine, Department of Obstetrics and Gynecology, Cornell University, New York, New York.
13
Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida.
14
Division of Hematology-Oncology, Department of Medicine, Massachusetts General Hospital, Boston.
15
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
16
Department of Obstetrics and Gynecology, Tufts Medical Center, Boston, Massachusetts.
17
Stephenson Cancer Center, Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City.
18
Sarah Cannon Research Institute, Nashville, Tennessee.
19
Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Washington, Seattle.
20
Department of Obstetrics and Gynaecology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
21
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
22
Division of Hematology/Oncology, Department of Medicine, The University of Alabama at Birmingham.
23
Department of Research & Early Development, TESARO: A GSK Company, Waltham, Massachusetts.
24
Department of Clinical Operations, TESARO: A GSK Company, Waltham, Massachusetts.
25
Department of Biostatistics, TESARO: A GSK Company, Waltham, Massachusetts.
26
Department of Clinical Science, TESARO: A GSK Company, Waltham, Massachusetts.
27
Helen Diller Family Comprehensive Cancer Center, Department of Medicine, University of California, San Francisco, Medical Center at Mount Zion, San Francisco.

Abstract

Importance:

Patients with recurrent ovarian carcinoma frequently develop resistance to platinum-based chemotherapy, at which time treatment options become limited.

Objective:

To evaluate the poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor niraparib combined with pembrolizumab in patients with recurrent ovarian carcinoma.

Design, Setting, and Participants:

The TOPACIO/KEYNOTE-162 (Niraparib in Combination With Pembrolizumab in Patients With Triple-Negative Breast Cancer or Ovarian Cancer) trial, an open-label, single-arm phases 1 and 2 study enrolled women with advanced or metastatic triple-negative breast cancer (TNBC) or recurrent ovarian carcinoma, irrespective of BRCA mutation status. Median follow-up was 12.4 months (range, 1.2 to ≥23.0 months). Data were collected from April 15, 2016, through September 4, 2018, with September 4, 2018, as a data cutoff, and analyzed from September 4, 2018, through January 30, 2019.

Interventions:

The recommended phase 2 dose (RP2D) was 200 mg of oral niraparib once daily and 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle.

Main Outcomes and Measures:

The primary objectives of phase 1 were to evaluate dose-limiting toxic effects and establish the RP2D and dosing schedule. The primary objective of phase 2 was to assess objective response rate (ORR; complete plus partial responses). Results from the phase 1 ovarian carcinoma and TNBC cohorts and phase 2 ovarian carcinoma cohort are reported. Because of the similarity in the phase 1 and 2 ovarian carcinoma populations, the data were pooled to perform an integrated efficacy analysis.

Results:

Fourteen patients (9 with ovarian carcinoma and 5 with TNBC) in phase 1 and 53 patients with ovarian carcinoma in phase 2 were enrolled, for a pooled ovarian carcinoma cohort of 62 patients (median age, 60 years [range, 46-83 years]). In the integrated efficacy phases 1 and 2 ovarian carcinoma population (60 of 62 evaluable patients), ORR was 18% (90% CI, 11%-29%), with a disease control rate of 65% (90% CI, 54%-75%), including 3 (5%) with confirmed complete responses, 8 (13%) with confirmed partial responses, 28 (47%) with stable disease, and 20 (33%) with progressive disease. The ORRs were consistent across subgroups based on platinum-based chemotherapy sensitivity, previous bevacizumab treatment, or tumor BRCA or homologous recombination deficiency (HRD) biomarker status. Median duration of response was not reached (range, 4.2 to ≥14.5 months). At data cutoff, 2 patients with a response and 1 patient with stable disease continued to receive treatment.

Conclusions and Relevance:

Niraparib in combination with pembrolizumab is tolerable, with promising antitumor activity for patients with ovarian carcinoma who have limited treatment options regardless of platinum status, biomarker status, or prior treatment with bevacizumab. Responses in patients without tumor BRCA mutations or non-HRD cancers were higher than expected with either agent as monotherapy.

Trial Registration:

ClinicalTrials.gov identifier: NCT02657889.

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center