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Expert Point of View: Padmanee Sharma, MD, PhD


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Padmanee Sharma, MD, PhD

Padmanee Sharma, MD, PhD

Discussant of the IMbassador250 trial, Padmanee Sharma, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, said: “These data indicate that neither anti–PD-1/PD-L1 monotherapy or the combination of anti–PD-1/PD-L1 with enzalutamide is likely to provide improved clinical benefit over standard-of-care agents for patients with metastatic castration-resistant prostate cancer whose disease progressed on prior hormonal therapy [abiraterone] and prior chemotherapy [docetaxel].”

Monotherapy trials of checkpoint inhibitors in metastatic castration-resistant prostate cancer suggest that combinations are needed to improve response rates, explained Dr. Sharma, but combination trials have been disappointing in prostate cancer thus far. The idea of adding a checkpoint inhibitor is to shift prostate cancer from being an immunologically “cold” tumor with few T cells to becoming more of a “hot” tumor.

“These studies did not indicate how these agents affect the tumor microenvironment,” she continued.

“There are few mutations in prostate cancer, and, as a result, the effector T cells may not be able to recognize an adequate number of antigens to mount a tumor response. The impact of enzalutamide on the microenvironment is unknown. Poor responses have been observed in prostate cancer after multiple prior therapies. There are multiple immunosuppressive pathways within the prostate tumor microenvironment, and PD-1/PD-L1–targeting agents may not sufficiently target all these immunosuppressive pathways,” noted Dr. Sharma. 

DISCLOSURE: Dr. Sharma holds stock or other ownership interests in Apricity, BioAtla, Codiak Biosciences, Constellation Pharmaceuticals, Dragonfly Therapeutics, Forty Seven, Hummingbird, ImaginAb, Jounce Therapeutics, Lytix Biopharma, Marker Therapeutics, Neon Therapeutics, Oncolytics, and Polaris; has an immediate family member who holds stock or other ownership interests in Apricity, BioAtla, Constellation Pharmaceuticals, Forty Seven, ImaginAb, Jounce Therapeutics, Lytix Biopharma, Marker Therapeutics, Neon Therapeutics, Polaris, and Tvardi Therapeutics; has served as a consultant or advisor to Achelois, Apricity, BioAtla, Bristol-Myers Squibb, Codiak Biosciences, Constellation Pharmaceuticals, Dragonfly Therapeutics, Forty Seven, Hummingbird, ImaginAb, Jounce Therapeutics, Lytix Biopharma, Marker Therapeutics, Neon Therapeutics, Oncolytics, Pieris Pharmaceuticals, and Polaris; has an immediate family member who has served as a consultant or advisor to Achelois, Apricity, BioAtla, Bristol-Myers Squibb, Codiak Biosciences, Constellation Pharmaceuticals, Dragonfly Therapeutics, Forty Seven, Hummingbird, ImaginAb, Jounce Therapeutics, Lytix Biopharma, Marker Therapeutics, Neon Therapeutics, Polaris, and Tvardi Therapeutics; holds a patent licensed to Jounce; and has an immediate family member who owns patents licensed to Bristol-Myers Squibb, Jounce, and Merck.


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The addition of the checkpoint inhibitor atezolizumab to enzalutamide failed to improve overall survival compared with enzalutamide alone in men with metastatic castration-resistant prostate cancer in the phase III IMbassador250 trial, according to results presented at the 2020 American Association ...

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