Sacituzumab govitecan effective in platinum-refractory metastatic urothelial cancer

Sacituzumab govitecan in combination with pembrolizumab demonstrated encouraging anti-tumour efficacy in patients with platinum-refractory metastatic urothelial cancer in Cohort 3 of the phase 2 TROPHY-U-01 trial.

Checkpoint inhibitors are standard therapy for patients with metastatic urothelial cancer after platinum-based regimens, with limited long-term disease control [1]. Sacituzumab govitecan is an antibody-drug conjugate composed of an anti-trophoblast cell-surface antigen 2 (Trop-2) antibody coupled with the topoisomerase-I inhibitor SN-38 [2]. In Cohort 1 of the phase 2 TROPHY-U-01 trial (NCT03547973), sacituzumab govitecan monotherapy demonstrated significant activity and manageable safety in patients with metastatic urothelial cancer who progressed after prior platinum-based chemotherapy and immune checkpoint inhibitor [3].

Cohort 3 of TROPHY-U-01 evaluated the efficacy and safety of combining sacituzumab govitecan with pembrolizumab as second-line therapy in immune checkpoint inhibitor-naïve patients with metastatic urothelial cancer who progressed after platinum-based chemotherapy. A total of 41 patients were enrolled and treated with sacituzumab govitecan plus pembrolizumab until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), and the interim results were presented by Dr Petros Grivas (University of Washington, WA, USA) [4].

At a median follow-up of 5.8 month, ORR was 34% (2% complete response, 32% partial response). The clinical benefit rate was 61%. Median duration of response was not yet reached, and the median PFS was 5.5 months. The most common treatment-emergent adverse events were diarrhoea, nausea, anaemia, neutropenia, and asthenia. Two patients discontinued treatment due to treatment-related adverse events.

Dr Grivas concluded that “in platinum-refractory metastatic urothelial cancer patients, sacituzumab govitecan in combination with pembrolizumab demonstrated encouraging ORR and clinical benefit rate, with an overall manageable safety profile. The data support further evaluation of sacituzumab govitecan plus an immune checkpoint inhibitor in metastatic urothelial cancer.”

1. Nadal R, et al. Cancer Treat Rev. 2019;76:10–21.
2. Goldenberg DM, et al. Expert Opin Biol Ther. 2020;20:871–885.
3. Tagawa, et al. J Clin Oncol. 2021;39:2474–2485.
4. Grivas P, et al. TROPHY-U-01 Cohort 3: Sacituzumab govitecan (SG) in combination with pembrolizumab (Pembro) in patients (pts) with metastatic urothelial cancer (mUC) who progressed after platinum (PLT)-based regimens. Abstract 434, ASCO GU 2022, 17–19 February.

 

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Posted on 8 April 202217 May 2024