Pembrolizumab/Olaparib Combo May Yield Better Responses in mCRPC Regardless of HRR Status

Article

Patients with metastatic castration-resistant prostate cancer experienced an improvement in prostate-specific antigen following treatment with pembrolizumab and olaparib.

Treatment with pembrolizumab (Keytruda) and olaparib (Lynparza) could help to improve prostate-specific antigen (PSA) response rates in patients with metastatic castration-resistant prostate cancer (mCRPC) regardless of homologous recombination repair (HRR) mutation status, according to findings from the KEYNOTE-365 trial (NCT02861573) that were presented at the 2021 European Society for Medical Oncology Congress.

The investigators also found high concordance between the Guardant Health (360 or Omni) assays and FoundationOne CDx for the detection of BRCA and HRR mutations.

The study included patients from cohort A of the KEYNOTE-365 trial, which investigated pembrolizumab at 200 mg IV every 3 weeks plus olaparib at 400 or 300 mg twice daily in patients with molecularly unselected, docetaxel-pretreated mCRPC.

For the current study, the investigators sought to “evaluate the prevalence of BRCA1 and/or BRCA2 mutations and other HRR mutations and their association with antitumor activity with pembrolizumab plus olaparib,” according to the study’s poster.

Primary end points included PSA response rate (50% or greater reduction from baseline), and objective response rate (ORR) per RECIST v1.1 by central review. Secondary end points included radiographic progression-free survival and overall survival.

The investigators assessed mutations in ctDNA using Guardant360 or GuardantOMNI assays. Guardant360 was used for detecting BRCA1, BRCA2, and ATM mutations. FoundationOneCDx was used to assess mutations in DNA isolated from formalin-fixed, paraffin-embedded tumor samples.

BRCA mutations were detected in 3 of 98 patients using Guardant360 or GuardantOMNI, and in 4 of 41 patients using FoundationOneCDx. HRR mutations were found in 14 of 59 patients using Guardant360 or GuardantOMNI and 12 of 41 patients using FoundationOneCDx.

PSA response was 50% in patients with a BRCA mutation (2 of 4 patients; 95% CI, 6.8%-93.2%) and 14% in patients without a BRCA mutation (13 of 95 patients; 95% CI, 7.5%-22.3%). In patients with an HRR mutation, PSA response was 22% (4 of 18 patients; 95% CI, 6.4%-33%) vs 13% in patients without an HRR mutation (7 of 52 patients; 95% CI, 5.6%-25.8%). ORR was 33% in patients with a BRCA mutation (1 of 3 patients; 95% CI, 0.8%-90.6%) and 6% in patients without a BRCA mutation (3 of 53 patients; 95% CI, 1.2%-15.7%). ORR was 8% in patients with an HRR mutation (1 of 12 patients; 95% CI, 0.2%-38.5%) and 3% in patients without an HRR mutation (1 of 30 patients; 95% CI, 0.1%-17.2%).

“There was high concordance between [Guardant360 or GuardantOMNI] assays and [FoundationOneCDx] for determination of BRCA (98% agreement) and HRR (87% agreement) mutational status,” the authors wrote in the study’s abstract.

“Caution should be used when interpreting these results because of small sample sizes,” they added.

Reference

Yu E, Piulats JM, Gravis G, et al. Association between homologous recombination repair mutations and response to pembrolizumab (pembro) plus olaparib (ola) in metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 Cohort A biomarker analysis. Paper presented at 2021 European Society for Medical Oncology Annual Congress; September 16-21, 2021; virtual. Abstract 73P.

Related Videos
Barbara Smith, MD, PhD, spoke about the potential use of pegulicianine-guided breast cancer surgery based on reports from the phase 3 INSITE trial.
Patient-reported symptoms following surgery appear to improve with the use of perioperative telemonitoring, says Kelly M. Mahuron, MD.
Treatment options in the refractory setting must improve for patients with resected colorectal cancer peritoneal metastasis, says Muhammad Talha Waheed, MD.
Although immature, overall survival data from the KEYNOTE-868 trial may support the use of pembrolizumab plus chemotherapy in patients with endometrial cancer.
Dostarlimab plus chemotherapy appears to yield favorable overall survival in patients with mismatch repair proficient endometrial cancer.
Some patients with large B-cell lymphoma may have to travel a great distance for an initial evaluation for CAR T-cell therapy.
Brian Slomovitz, MD, MS, FACOG discusses the use of new antibody drug conjugates for treating patients with various gynecologic cancers.
Education is essential to referring oncologists manage toxicities associated with CAR T-cell therapy for patients with large B-cell lymphoma.
There is no absolute age cutoff where CAR T cells are contraindicated for those with large B-cell lymphoma, says David L. Porter, MD.
David L. Porter, MD, emphasizes referring patients with large B-cell lymphoma early for CAR T-cell therapy consultation.
Related Content