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Key Takeaways from KEYNOTE-365 in Metastatic Castration-Resistant Prostate Cancer

Evan Y. Yu, MD
Published Online:1:00 PM, Thu July 18, 2019


Evan Y. Yu, MD, professor, Department of Medical Oncology, University of Washington School of Medicine, member, Clinical Research Division, Fred Hutchinson Cancer Research Center, and clinical trials core director, Genitourinary Medical Oncology, Seattle Cancer Care Alliance, discussed the key takeaways from the phase Ib/II KEYNOTE-365 trial, which evaluated different novel pembrolizumab (Keytruda) combinations in patients with metastatic castration-resistant prostate cancer (mCRPC).

Forty-one patients were treated in cohort A with pembrolizumab plus olaparib (Lynparza); this combination induced modest response rates in the molecularly unselected patients with mCRPC. This represents a heavily pretreated patient population, where about 25% of patients had previously received all available treatment strategies, including abiraterone acetate (Zytiga), enzalutamide (Xtandi), docetaxel, and cabazitaxel (Jevtana), according to Yang.

The overall response rate (ORR) was 7% at a median follow-up of 11.4 months, and while this ORR is small, it is significant for this patient population, says Yang. In patients with soft tissue disease, 14% had a significant PSA decline (≥50%), compared to 12% in the overall population.

Yang says it is hard to confirmprogression in nontarget lesions such as bone metastases, or in bone scans that may look worse. In all but 1 of the patients who responded, they had progressed in nontarget lesions and bone lesions. Yang says it’s common to see responses with immunotherapy, but it’s rare to see a short-term response followed by progression elsewhere.

One possibility for this is that the bone and soft tissue microenvironments are different in mCRPC, so perhaps this treatment would work better for soft tissue. Yang concludes that these hypotheses must be validated.
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