During a Targeted Oncology™ Case-Based Roundtable™ event, Pedro C. Barata, MD, MSc, discussed data supporting the use of sacituzumab govitecan in advanced urothelial carcinoma.
Targeted Oncology: What led to the use of sacituzumab govitecan (Trodelvy) in patients with metastatic urothelial cancer?
PEDRO C. BARATA, MD, MSc: Trop-2 happens to be highly expressed in urothelial carcinoma. It’s an epithelial cell surface. Sacituzumab govitecan is different from other antibody-drug conjugates. Here you have a Trop-2 target or Trop-2-directed therapy, and govitecan is the SN-38 which is we know is the active compound of irinotecan. It’s a topoisomerase inhibitor as the payload, tagged with an antibody towards Trop-2. The data across solid tumors is interesting, with overall response rates [ORR] over 30%, median progression-free survival [PFS] of 7.3%, and a very manageable safety profile.1 For that reason, it ended up getting accelerated approval for triple-negative breast cancer.2 It also got a fast-track designation and accelerated approval for metastatic urothelial carcinoma.3 We are waiting for the phase 3 confirmatory trial regarding sacituzumab.
The TROPHY U-01 trial [NCT03547973] had 3 cohorts. There were more [cohorts but I will] talk about these 3. Cohort 1 included 100 patients with metastatic urothelial carcinoma progressing after a platinum-based chemotherapy and an immunotherapy. Cohort 2 included patients with advanced urothelial carcinoma who could not get platinum-based chemotherapy, but they did progress on immunotherapy. Cohort 3 included immunotherapy-naïve patients who progressed on platinum. We are talking about a 200-patient study on these 3 cohorts, 100 for Cohort 1 and then 40 or 60 in cohorts 2 and 3. ORR was the primary end point.
What were the results for patients who were enrolled after progressing on platinum-based therapy and immune checkpoint inhibitor therapy?
[Looking at the baseline characteristics] for Cohort 1, these patients were pretreated and half of them got 3 or more lines of treatment.4 A third had liver metastases. Everyone was exposed to platinum therapy. Two patients were exposed to erdafitinib [Balversa]. The median number of prior treatments was 3 for metastatic disease, and you do have a fair number of patients with 2 or 3 prognostic risk factors. I would argue that it's a heavily treated population.
In the Cohort 1, final results showed the ORR was 27%, including 5.3% complete responses, and the rest were partial responses, 22%. When patients responded, the duration of response was 7.2 months, which is similar to what we were seeing in other tumors. But the bottom line is the ORR was stable throughout and in different subsets of patients, including those who received enfortumab vedotin [Padcev]. Three patients out of 10 had enfortumab vedotin as prior therapy.
The median PFS was close to 6 months [5.4 months, 95% CI, 3.5-7.2]. Overall survival was closer to a year [10.9 months, 95% CI, 9.0-13.8].
What was the safety profile of sacituzumab in these patients?
[Looking at] the safety with treatment-related adverse events [AEs] of any grade and then significant grade 3 and 4 toxicities, neutropenia can occur [frequently (46% of any grade)]. Cytopenias like leukopenia, can occur, and there is some anemia and some diarrhea. What is remarkable to me is the number of AEs that have 0 grade 4 AEs. There are double digits for the hematologic AEs or the cytopenias. Everything else is in the single digits, even for grade 3. For most patients, they do well.
You can debate what to do about the neutropenia. I have to highlight the 30% who got G-CSF [granulocyte colony-stimulating factor] in this cohort, and 6% needed to discontinue treatment due to AEs, and that was commonly neutropenia. They had 1 treatment-related death, [which was because of] febrile neutropenia.
I think we’re very familiar with this [toxicity profile]. We use topoisomerase inhibitors. We use irinotecan and others, and so we know what topoisomerase inhibitors do. I do have the sense that this is somewhat familiar to [oncologists] because some of us are treating other cancers where we’re using topoisomerase inhibitors.
1. Tagawa ST, Faltas BM, Lam ET, et al. Sacituzumab govitecan (IMMU-132) in patients with previously treated metastatic urothelial cancer (mUC): Results from a phase I/II study. J Clin Oncol. 2019;37(7_suppl):354. doi:10.1200/JCO.2019.37.7_suppl.354
FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer. FDA. Published April 22, 2020. Accessed June 13, 2023. https://bit.ly/3NarQav
3. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed June 13, 2023. https://bit.ly/2QoWumx
4. Tagawa ST, Balar AV, Petrylak DP, et al. TROPHY-U-01: a phase II open-label study of sacituzumab govitecan in patients with metastatic urothelial carcinoma progressing after platinum-based chemotherapy and checkpoint inhibitors. J Clin Oncol. 2021;39(22):2474-2485. doi:10.1200/JCO.20.03489