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Pembrolizumab plus Enzalutamide in metastatic castration resistant prostate cancer


Anti-PD1 treatment with Pembrolizumab ( Keytruda ) is a promising treatment strategy in many solid tumors.
Researchers have reported clinical outcomes of adding Pembrolizumab to men with metastatic castration resistant prostate cancer ( mCRPC ) progressing on Enzalutamide.

A total of 28 patients with mCRPC who had not previously had chemotherapy for mCRPC or checkpoint inhibitors, was enrolled.
Pembrolizumab was given 200 mg IV every 3 weeks for 4 doses, which could be repeated for the patients who had stable or responsive disease.

The primary endpoint was prostate specific antigen ( PSA ) response ( PSA decline of greater than or equal to 50% ).
Secondary endpoints were radiographic objective response ( RECIST 1.1 ), PSA progression free survival, time to subsequent treatment, and time to death from any cause.

Baseline tumor biopsies were done if there was a metastatic deposit amenable to biopsy.

Five of 28 patients ( 18% ) had a PSA decline of greater than or equal to 50%. Three of 12 patients ( 25% ) with measurable disease at baseline achieved an objective response on radiographs.
Of the responders, one passed away from an unrelated cause without PSA recurrence after 14.2 months, and one relapsed after 10 months and did not respond to a second course of Pembrolizumab. The other 3 continue to be in response ( range 21.9-33.8 months ).

For the entire cohort, the median follow up was 22.7 months, and the median PSA-PFS [ progression-free survival ] time was 3.8 months ( 95% CI: 2.8 – 9.9 months ).
Time to subsequent treatment was 8.2 months ( 95% CI: 5.1 – 12.8 months ).

Median overall survival was 22.2 months ( 95% CI: 14.7 – 28 .4 months ).

Median radiographic PFS was 10.8 months ( 5-22 months ).

There were 8 immune related adverse events in 7 unique patients ( hypothyroid 3, hyperthyroid 1, myositis 2, colitis 2 ).

Seventeen patients had baseline biopsies of a metastatic deposit: 3 responders, 14 non-responders. Of the 3 responders who had baseline biopsies, one had MSI and DNA repair defects. The other 2 had neither.
Of the non-responders who had sequencing, 4 had a DNA repair defects, and none had MSI.

None of the biopsies showed tumoral PD-L1 expression ( Qualtek, 22C3 ).

In conclusion, Pembrolizumab has activity in mCRPC when added to Enzalutamide. Responses were deep and durable in a subset of patients. ( Xagena )

Source: ASCO ( American Society of Clinical Oncology ) Meeting, 2018

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