Dr Park on the Use of Sacituzumab Govitecan Plus Pembrolizumab in 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%).