Efficacy and Safety of Sacituzumab Govetican for Patients With Advanced Endometrial Cancer

Results from TROPiCS-03

Alessandro Santin, MD, Yale Cancer Center, New Haven, Connecticut, discusses results from a cohort of patients with endometrial cancer within the TROPiCS-03 trial, evaluating the trophoblast cell-surface antigen 2 (Trop 2)-directed antibody-drug conjugate sacituzumab govetican. Among this population of heavily pretreated patients with advanced endometrial cancer, sacituzumab govetican showed promising efficacy and manageable safety.

Dr Santin highlighted the importance of these results, stating, “patients with advanced recurrent endometrial cancer that progressed on chemotherapy as well as immune checkpoint inhibitors…have very few effective therapeutic options available, and they have a short prognosis in short term.”

Transcript:

I'm Alessandro Santin. I'm a professor of obstetric and gynecology at Yale University School of Medicine, and I'm the co-chief of the division of Gynecologic Oncology at Yale University School of Medicine.

The plan today is to discuss the efficacy and safety of Sacituzumab Goan in patients with advanced endometrial carcinoma. And in particular, the recent publication in JCO of the endometrial cancer cohort. Briefly TROPiCS-03 was a multi cohort open label phase 2 basket trial, in multiple solid tumor patients. In this study, we enrolled a total of 41 endometrial cancer patients with recurrent, measurable disease. Eligible patients with recurrent endometrial cancer received sacituzumab govetican, also known as Trodelvy, at the dose of 10 mg per kg on day 1 and day 8, every 3 weeks.

The primary end point of the study was objective response rate reported per RECIST 1.1 criteria, while the secondary end point of the study included clinical benefit rate, that was complete plus partial responses, stable disease at 6 months, duration of response, progression free survival (PFS), overall survival, and safety. Finally, we also assessed Trop 2 expression in the tumor of these patients’ immunohistochemistry, with the ultimate goal to correlate expression with clinical activity.

Our results demonstrated that after a median follow up of 5.8 months about 22% of patients responded with a confirmed partial response. However, again, 61% of all of the patients demonstrated a decrease in the target size of the lesions. The clinical benefit rate was 32% combining CR and PR and the stable disease for 6 months. The median duration of response of the study was 8.8 month with a median PFS of 4.8 0.8 month.

Trop 2 expression was conducted on the total of 39 out of the 41 patient. What we found was that over 90% of these tumors overexpressed Trop 2 protein level. Therefore we found limited correlation with efficacy, because the overwhelming majority of this tumor, once again, over-expressed Trop 2. Grade 3 or more treatment-related adverse events were detected in about 73% of the patients. However, these treatment-related adverse events were manageable with dose interruption or dose reduction. The fact that these side effects were somehow manageable is also supported by the fact that less than 5% of these patients stopped treatment because of grade 3 or more adverse events.

In conclusion, the finding from the TROPiCS-03 study demonstrate encouraging activity of sacituzumab govetican in a heavily pretreated population of advanced endometrial cancer with measurable disease and the toxicity of sacituzumab govetican was again manageable. This study is of course, therefore important because patients with advanced recurrent endometrial cancer that progressed on chemotherapy as well as immune checkpoint inhibitors, over 85% of the patient enrolled in this trial have very few effective therapeutic options available, and they have a short prognosis in short term.

Source:

Santin A, Corr BR, Spira A, et al. Efficacy and safety of sacituzumab govetican in patients with advanced solid tumors (TROPiCS-03): Analysis in patients with advanced endometrial cancer. J Clin Oncol. Published online: July 31, 2024. doi:10.1200/JCO.23.02767