Pivotal data published for sacituzumab govitecan in bladder cancer
The results of the pivotal phase 2 TROPHY-U-01 trial, which led to the accelerated FDA approval of sacituzumab govitecan (Trodelvy) for advanced urothelial cancer, have now been published in the Journal of Clinical Oncology.1.2
Data from cohort 1 of the study showed that at a median follow-up of 9.1 months, sacituzumab govitecan induced an overall response rate (ORR) of 27% in patients with local urothelial carcinoma. advanced or metastatic (UC) following failure of both chemotherapy and checkpoint inhibition. In addition, 77% of the patients had a measurable decrease in disease.
There were 31 responders, including 6 (5%) complete responses (CR) and 25 (22%) partial responses (PR), according to the results presented at the ESMO 2020 meeting.3 The median duration of response with the antibody conjugate -medication (ADC) was 7.2 months.
“Sacituzumab govitecan is an active drug with a manageable safety profile with the most common toxicities of neutropenia and diarrhea. Sacituzumab govitecan has notable efficacy over historical controls in pretreated mUC which has progressed on both platinum-based chemotherapy regimens and checkpoint inhibition, ”Principal Investigator 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 the co-authors wrote in their study conclusion.
The global open-label 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 not eligible for platinum-based chemotherapy and who progressed after checkpoint inhibition (cohort 2); and those who have never received checkpoint inhibitors but have progressed on platinum-based therapy (cohort 3).
In cohort 1, which patients received 10 mg / kg ADC on days 1 and 8, every 21 days and continued treatment until loss of clinical benefit or intolerable toxicity. The primary endpoint of this analysis was ORR by central review.
Among the patients evaluated, the median age was 66 years, with 23% of patients 75 years or older and 78% male. Additionally, the majority of patients were 74% white. Twenty-eight percent of patients had an ECOG performance index of 0, while 72% had a status of 1. Overall, 66.4% of patients had visceral metastases. The median number of previous cancer regimens received was 3 (range: 1 to 8).
Sixteen (14%) of 113 evaluable patients continued to receive treatment with sacituzumab govitecan at the time of analysis. The majority of patients who discontinued treatment did so because of disease progression (66%; n = 75). Only 7% (n = 8) of patients discontinued ADC due to toxicity. Three percent of patients (n = 3) discontinued due to withdrawal of consent and 3% (n = 3) died. The median duration of treatment was 3.7 months and the maximum duration of treatment so far is 16 months. Fifty percent of patients (n = 56) are in survival follow-up.
The median time to onset of response was 1.6 months. The reported ORR, median ORD, and median time to response were consistent with investigator ratings. The median progression-free survival and overall survival were 5.4 and 10.9 months, respectively.
Regarding safety, diarrhea was the most frequently experienced treatment-related adverse reaction, occurring in two-thirds of patients (all grades, 65%); this is consistent with what has been reported in previous studies with ADC. However, most of these effects were grade 1/2.
Grade 3 diarrhea occurred in 9% of patients, with only 1% of grade 4. Forty-six percent of patients experienced neutropenia, 22% having a grade 3 effect and 12% reporting a grade 4 effect. Neutropenia was manageable and with dose reductions and a 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. In addition, 1 treatment-related death was reported in a patient with sepsis due to febrile neutropenia.
To ensure that clinicians closely monitor 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 fast-track approval policy, the approval continue is based on the results of a confirmatory test, such as TROPiCs-04.
1. Tagawa ST, Balar AV, Petrylak DP et al. TROPHY-U-01: An open-label phase II study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors [published online ahead of print April 30, 2021]. J Clin Oncol. doi: 10.1200 / JCO.20.03489
2. FDA grants expedited approval to sacituzumab govitecan for advanced urothelial cancer. Published online April 13, 2021. Accessed May 7, 2021. https://bit.ly/3mI4xap.