Dr Park on the Use of Sacituzumab Govitecan Plus Pembrolizumab in Urothelial Carcinoma

Commentary
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Chandler H. Park, MD, FACP, discusses the use of sacituzumab govitecan plus pembrolizumab in patients with metastatic urothelial carcinoma.

Chandler H. Park, MD, FACP, medical oncologist, Norton Healthcare, discusses outcomes from cohort 3 of the phase 2 TROPHY-U-01 trial (NCT03547973) investigating sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) in patients with metastatic urothelial carcinoma who have progressed following platinum-based chemotherapy.

The TROPHY-U-01 clinical trial is a multicohort, open-label investigation. Enrolled patients were checkpoint inhibitor–naive and displayed progression within 12 months post–platinum-based chemotherapy in the metastatic setting or neoadjuvant setting. Patients were treated with 10 mg/kg of sacituzumab govitecan once on days 1 and 8 of each 21-day cycle alongside 200 mg of pembrolizumab once on day 1 within each cycle. The primary end point evaluated was objective response rate (ORR) per central review. Secondary end points encompassed clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS) per central review, and safety. 

Park begins by stating that regarding the combination of post-platinum chemotherapy and pembrolizumab, initial findings from single-agent pembrolizumab studies indicated response rates of approximately 20% to 21%. TROPHY-U-01 investigators examined whether the combination of an antibody-drug conjugate, such as sacituzumab govitecan, and pembrolizumab could enhance the response rates, prolong the DORs, and increase the CBRs seen with single-agent pembrolizumab in patients with metastatic urothelial cancer.

In terms of outcomes, cohort 3 comprised 41 patients with a median age of 67 years (range, 46-86), 83% of whom were male. At a median follow-up of 14.8 months (95% CI, 12.6-16.8), the ORR stood at 41% (95% CI, 26.3%-57.9%), with 20% of patients achieving a complete response, Park adds. Notably, the CBR was 46% (95% CI, 30.7%-62.6%), the median DOR was 11.1 months (95% CI, 4.8-not estimable [NE]), and the median PFS was 5.3 months (95% CI, 3.4-10.2).

Moreover, the median overall survival was 12.7 months (range, 10.7-NE), Park concludes. Grade 3 or greater treatment-related adverse effects were observed in 61% of patients, with the most prevalent being neutropenia (37%), leukopenia (20%), and diarrhea (20%).

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