Sacituzumab Govitecan Continues to Show Efficacy in Pretreated mUC

Daniel P. Petrylak, MD

Treatment with sacituzumab govitecan-hziy (Trodelvy) showed notable efficacy and a manageable safety profile for patients with advanced or unresectable or metastatic urothelial carcinoma (mUC) who had progressed after prior platinum-based combination chemotherapy and checkpoint inhibitors (CPIs), according to promising data shown in the primary analysis of TROPHY-U-01 (NCT03547973) cohort 2.¹

In the study, investigators evaluated sacituzumab govitecan in patients advanced or unresectable or mUC who had progressed after prior platinum-based combination chemotherapy and checkpoint inhibitors (CPIs).² Patients were treated with sacituzumab govitecan 10 mg/kg on days 1 and 8 of 21-day cycles.

The primary end point of the study was centrally reviewed overall response rate, along with the secondary end points of progression-free survival, overall survival, duration of response, and safety.

Among the 38 patients enrolled in cohort 2 of the study, there were 12 responses to sacituzumab govitecan, all of which were partial and lasted for a median duration of 5.6 months (95% CI, 2.8-13.3). The median progression-free survival (PFS) after a median follow-up of 9.3 months (range, 0.5-30.6) was 5.6 months (95% CI, 4.1-8.3), and the median overall survival (OS) was 13.5 months (95% CI, 7.6-15.6).

For safety, 68% of patients had a grade 3 or higher treatment-related adverse events (TRAEs), including neutropenia (34%), anemia (21%), leukopenia (18%), fatigue (18%), and diarrhea (16%). The most common all-grade TRAEs included diarrhea (63%), alopecia (50%), nausea (47%), neutropenia (45%), fatigue (42%), anemia (37%), leukopenia (34%), and decreased appetite (26%). Eight percent of patients experienced treatment-related febrile neutropenia, of which 2 cases were grade 3 and 1 was grade 4 in severity. Moreover, no treatment-related deaths were reported in the study.

Overall, these results support further investigation of sacituzumab govitecan monotherapy or given in combination for patients with mUC who progressed after prior CPI therapy.

In an interview with Targeted Oncology^TM, Daniel P. Petrylak, MD, professor of medicine and urology at Yale School of Medicine, and co-leader, Cancer Signaling Networks, Yale Cancer Center, discussed findings from the TROPHY-U-01 study for patients with mUC, and what the next steps for research are.

Targeted Oncology: What should oncologists know about the TROPHY-U-01 study?

Petrylak: Sacituzumab govitecan is an ADC that recognizes TROP-2, which is expressed in a number of different tumors. It also delivers SN-38, which is a topoisomerase inhibitor. The TROPHY trial has 6 different cohorts. This is the second cohort which was evaluating sacituzumab govitecan in those patients who were ineligible to receive platinum. What we found was that there was a 32% response rate in these patients. In those patients who had not had prior chemotherapy, those who had not had enfortumab vedotin [Padcev] the response rate was 50%. This is looking active in this group of patients. The characteristics of patients we included showed they could have received prior immunotherapy, and they could have received prior chemotherapy in the neoadjuvant setting. It's a group of patients that there are few treatments available for and we're excited about the data.

Are there any next steps for this research?

There are multiple cohorts that are open for the TROPHY study. There are other combinations that have been evaluated, including sacituzumab combined with pembrolizumab, so that's where I see the further research with this going.

What are some of the key takeaways for urologists?

Bladder cancer previously was a disease that once a patient progressed after primary chemotherapy, there was little that could be done. Now, with the checkpoints, with the ADCs, we have active drugs that can be administered to patients that can significantly improve their survival, as well as their quality of life.

What changes are you expecting in the mUC landscape in the near future?

We're seeing a shift in where these drugs are moving. We're seeing the move to the earlier setting, particularly since these drugs do have activity in visceral disease, particularly liver metastases. These drugs are moving earlier, not only to the frontline setting, but to the neoadjuvant setting as well. We're seeing that there's going to be a shift in how these drugs are used.

REFERENCE:

Petrylak DP, Tagawa ST, Jain RK, et al. Primary analysis of TROPHY-U-01 cohort 2, a phase 2 study of sacituzumab govitecan (SG) in platinum (PT)-ineligible patients (pts) with metastatic urothelial cancer (mUC) that progressed after prior checkpoint inhibitor (CPI) therapy. J Clin Oncol. 2023;41(suppl 6):520. doi:10.1200/JCO.2023.41.6_suppl.520