FDA approves sacituzumab govitecan for bladder cancer

April 13, 2021
Jason M. Broderick

The FDA has granted an accelerated approval to sacituzumab govitecan (Trodelvy) for the treatment of patients with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a PD-1 or PD-L1 inhibitor.1,2

The approval of the antibody-drug conjugate (ADC) was based on the final data from cohort 1 of the phase 2 TROPHY-U-01 trial, which showed that sacituzumab govitecan induced an overall response rate (ORR) of 27% in heavily pretreated patients with mUC following the failure of both platinum-based chemotherapy and checkpoint inhibition.

There were 31 responders, including 6 (5%) complete responses (CRs) and 25 (22%) partial responses (PRs), according to findings presented during the 2020 ESMO Congress.3 The median response duration with the ADC was 7.2 months.

“Only a fraction of patients derives long-term benefit from previously approved cytotoxic therapy or immunotherapy, leaving a great unmet need for treatment options for patients with advanced urothelial cancer who have progressed on first- and second-line therapies,” Scott T. Tagawa, MD, MS, FACP, professor of Medicine and Urology at Weill Cornell Medicine, an oncologist at New York-Presbyterian/Weill Cornell Medical Center, and principal investigator of the TROPHY study, stated in a press release.2

“The response rate and tolerability seen with sacituzumab govitecan-hziy may provide physicians an effective new treatment option for patients whose cancer continues to progress even after multiple therapies,” added Tagawa.

The open-label, global phase 2 TROPHY-U-01 trial evaluated sacituzumab govitecan in 3 cohorts: patients with metastatic urothelial carcinoma who progressed on platinum-based chemotherapy and checkpoint inhibition (cohort 1); those who were ineligible for platinum-based chemotherapy and progressed following checkpoint inhibition (cohort 2); and those who never received checkpoint inhibitors but had progressed on platinum-based therapy (cohort 3).

The findings shared at ESMO were from cohort 1, which patients received 10 mg/kg of the ADC on days 1 and 8, every 21 days and continued treatment until loss of clinical benefit or intolerable toxicity. The primary end point of this analysis was ORR per central review.

Among the evaluated patients, the median age was 66 years, with 23% of patients 75 years of age or older and 78% male. Moreover, the majority of patients were white, at 74%. Twenty-eight percent of patients had an ECOG performance status of 0, while 72% had a status of 1. Overall, 62% of patients had visceral metastases; 40% had lung metastases, 28% had liver metastases, and 12% had other. The median number of prior anticancer regimens received was 3.

Sixteen (14%) of 113 evaluable patients continued to receive treatment with sacituzumab govitecan at the time of the analysis. The majority of patients who discontinued treatment did so because of disease progression (66%; n = 75). Only 7% (n = 8) of patients discontinued the ADC because of toxicity. Three percent of patients (n = 3) discontinued because of withdrawn consent and 3% (n = 3) died. The median time on treatment was 3.7 months, and the maximum time on treatment is 16 months thus far. Fifty-percent of patients (n = 56) are in follow-up for survival.

The median time to onset of response was 1.6 months. The ORR, median DOR, and median time to response reported were consistent with investigator assessments.

Regarding safety, diarrhea was the most commonly experienced treatment-related adverse effect, occurring in two-thirds of patients (all grade, 65%); this is consistent with what has been reported in prior studies with the ADC. However, most of these effects were grade 1/2.

Grade 3 diarrhea occurred in 9% of patients, with only 1% experiencing grade 4. Forty-six percent of patients experienced neutropenia, with 22% having a grade 3 effect and 12% reporting a grade 4 effect. Neutropenia was manageable and with dose reductions and granulocyte colony-stimulating factor, it was reversible. Thirty-percent of patients received GCSF either as primary prophylaxis or in response to neutropenia, according to study investigators. Moreover, 1 treatment-related death was reported, with a patient presenting with sepsis due to febrile neutropenia.

To ensure clinicians closely monitor for these specific adverse events, the FDA label for sacituzumab govitecan includes a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea.

The phase 3 TROPiCs-04 trial (NCT04527991), which is currently recruiting patients, is being launched to confirm these promising phase 2 results. Based on the FDA's accelerated approval policy, continued approval is based on findings from a confirmatory trial, such as TROPiCs-04.


1. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. Posted online April 13, 2021. Accessed April 13, 2021. https://bit.ly/3mI4xap.

2. U.S. FDA Grants Accelerated Approval to Trodelvy® for the Treatment of Metastatic Urothelial Cancer. Gilead Sciences. Published online April 13, 2021. Accessed April 13, 2021. https://bwnews.pr/3uO05tt.

3. Loriot Y, Balar AV, Petrylak DP, et al. Final results from TROPHY-U-01 cohort 1: a phase 2 open-label study of sacituzumab govitecan (SG) in patients with metastatic urothelial cancer (mUC) and disease progression after platinum (PLT)-based regimens and checkpoint inhibitors. Presented at: 2020 ESMO Virtual Congress; September 19-21, 2020; Virtual. Abstract LBA24.