Guru P. Sonpavde, MD, Director of the Bladder Cancer Program at Dana-Farber Cancer Institute, Boston, said the therapeutic landscape of urothelial cancer has been altered by PD-L1 inhibitors and antibody-drug conjugates. “The rationale for Cohort 3 was based on high response rates seen with a similar combination as first-line therapy for cisplatin-ineligible patients,” he noted. “The combination [of sacituzumab govitecan-hziy plus pembrolizumab] was active, and objective responses were seen regardless of the sites of metastasis. This is reassuring. Toxicity was as expected.”
Dr. Sonpavde cited some patient selection issues for this trial and perhaps a need for more intensive therapy for some. “More than 70% had visceral disease. There was a short treatment-free interval, and this group of patients had low response rates to prior platinum,” he stated.
Guru P. Sonpavde, MD
“Antibody-drug conjugates are the way forward for urothelial cancer,” he continued. “Multiple phase III trials are looking at these agents as first-line therapy. Several combination regimens incorporating sacituzumab vedotin or enfortumab vedotin-ejfv [another antibody-drug conjugate] are being studied in urothelial cancer. They include the combination of immune checkpoint inhibitor plus antibody-drug conjugate, a combination of both sacituzumab vedotin and enfortumab vedotin, and a combination of a PARP [poly (ADP-ribose) polymerase] inhibitor plus sacituzumab vedotin.
Questions Remain
Dr. Sonpavde mentioned that the following questions remain: Would we do better with a biomarker for patient selection? Is there an optimal setting for these combinations?
“Sacituzumab vedotin did not play that well with pembrolizumab,” according to Dr. Sonpavde.
DISCLOSURE: Dr. Sonpavde reported financial relationships with Astellas Pharma, AstraZeneca, Bavarian Nordic, Bicycle Therapeutics, Bristol Myers Squibb, Debiopharm Group, Eisai, Elsevier, EMD Serono, Exelixis, G1 Therapeutics, Genentech, Gilead Sciences, Infinity Pharmaceuticals, Janssen, Loxo/Lilly, Merck, Mereo BioPharma, Pfizer, QED Therapeutics, Scholar Rock, and Seattle Genetics.
