Outcomes of First-line Chemotherapy and Second-line Immune Checkpoint Inhibitor in Patients with Advanced Urothelial Carcinoma

The optimal pairings of regimens across first- and second-line therapy regimens for patients with advanced urothelial carcinoma are unknown. Miron et al. sought to determine the effects of different combinations of first-line platinum-based chemotherapy and second-line immunotherapy on patient survival. The investigators collected patient data from the Flatiron Health electronic health record-derived de-identified database, resulting in a cohort of 2,042 patients who fit the inclusion criteria. Of these patients, 1,002 received gemcitabine and cisplatin, and 1,040 received gemcitabine and carboplatin. Researchers then identified 890 patients who received single-agent second-line immune checkpoint inhibitor therapy. Unadjusted overall survival from the initiation of second-line therapy was longer in patients treated with gemcitabine and cisplatin than in those treated with gemcitabine and carboplatin. However, in an adjusted Cox proportional hazards model, there was no statistically significant difference in overall survival based on the first-line chemotherapy regimen. Variables associated with increased risk of death on second-line immune checkpoint inhibitor treatment were low baseline hemoglobin, liver metastasis, ureter as the primary tumor site, ECOG performance status, and elevated neutrophil to lymphocyte ratio.

In a model that evaluated the risk of death across treatment regimens, the combination of first-line gemcitabine and cisplatin treatment was associated with better outcomes. Furthermore, patients who received gemcitabine and cisplatin followed by a second-line non-immune checkpoint inhibitor treatment also exhibited a survival advantage. A more detailed analysis of patients who were alive, progression-free, and not on second-line therapy at 12 and 24 months revealed that a more significant proportion of patients who met these criteria had received gemcitabine and cisplatin as a first-line regimen.

Overall, the findings from this study reveal distinct differences in patient outcomes depending on the combination of first-line treatment and the choice of second-line treatment. Gemcitabine and cisplatin treatment was associated with improved survival, and immune checkpoint inhibitors were found to modify the risk of death. Cisplatin has been suggested to alter the immune microenvironment favorably for subsequent response to immune checkpoint inhibitor therapy. These findings can help inform choices regarding the sequencing of treatment regimens.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine, New York City, New York

References:

Miron B, Handorf E, Zarrabi K, et al. Influence of first-line chemotherapy regimen on survival outcomes of patients with advanced urothelial carcinoma who received second-line immune checkpoint inhibitors [published online ahead of print, 2022 Jul 2]. Urol Oncol. 2022;S1078-1439(22)00210-1. doi:10.1016/j.urolonc.2022.05.028.

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