Efficacy of platinum re-challenge in metastatic urothelial carcinoma (mUC): A retrospective comparison of chemotherapy regimens.
Authors: Wong Risa Liang , Ferris Lorin , Do Olivia A , Holt Sarah K , Ramos Jorge , Crabb Simon J. , Sternberg Cora N. , Bellmunt Joaquim , Ladoire Sylvain , De Giorgi Ugo , Harshman Lauren C , Vaishampayan Ulka N. , Necchi Andrea , Srinivas Sandy , Pal Sumanta K. , Niegisch Guenter , Dorff Tanya B. , Galsky Matt D. , Yu Evan Y. ,   Retrospective International Study of Cancers of the Urothelium (RISC)
Published: March 2021

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Background: First-line platinum-based combination chemotherapy (fPBC) is standard of care for fit patients with mUC. Further lines of therapy include immuno-oncology agents, erdafitinib, and enfortumab vedotin, but patients ineligible for these therapies or who subsequently progress may be considered for further chemotherapy. As the choice of chemotherapy regimen is unclear for these patients, we compared the efficacy of subsequent platinum-based chemotherapy (sPBC) and subsequent non-platinum-based chemotherapy (sNPBC) in patients with mUC. Methods: Data was analyzed from the Retrospective International Study of Cancers of the Urothelium (RISC), comprising patients from 28 international centers treated 2005-2012. Inclusion criteria were diagnosis of mUC, receipt of fPBC for mUC, and receipt of ≥2 cycles of subsequent chemotherapy. Patients who had received prior platinum-based chemotherapy in the non-metastatic setting were excluded. A multivariate Cox proportional hazards model was used to compare overall survival (OS), while χ2 and student’s t-test were used for univariate analyses. A two-sided p value of <0.05 was considered statistically significant. Results: Of 296 patients, 135 received sPBC and 161 received sNPBC. Common sNPBC regimens contained gemcitabine, taxanes, or pemetrexed. Baseline characteristics were similar, including Charlson Comorbidity Index (CCI) and performance status (PS), except more patients in the sPBC group had achieved investigator-designated stable disease or response (SD/R) with fPBC (75.4% vs. 63.3%, p = 0.031) and had higher hemoglobin values (median 11.9 vs. 11.1 g/dL, p = 0.004). OS was superior for patients receiving sPBC (median 7.9 months) compared to sNPBC (median 5.5 months) after adjusting for CCI, PS, presence of liver metastases, time since fPBC, and number of fPBC cycles received (HR 0.72, 95% CI 0.53-0.98, p = 0.035). 70 patients (57.4%) achieved SD/R with sPBC and 65 (44.8%) with sNPBC (p = 0.041). Achieving SD/R with subsequent chemotherapy was not associated with number of fPBC cycles received, but for sPBC was associated with longer time since fPBC (median 5.9 vs. 2.9 months, p = 0.033); the same was not true for sNPBC (median 2.2 vs. 2.6 months, p = 0.057). Achieving SD/R with fPBC was associated with greater likelihood of SD/R with sPBC (63.2% vs. 29.6%, p = 0.002), but not sNPBC (50.5% vs. 38.8%, p = 0.185). Liver metastases were negatively associated with likelihood of SD/R with sPBC (43.8% vs. 63.6%, p = 0.038), but not sNPBC (36.2% vs 49.0%, p = 0.147). Conclusions: After treatment with fPBC for mUC, patients able to receive sPBC had better OS compared to those who received sNPBC in a multivariate model. Patients were also more likely to achieve SD/R with sPBC; factors associated with achieving SD/R with sPBC but not sNPBC included longer interim since fPBC, achieving SD/R to fPBC, and absence of liver metastases.