(UroToday.com) The 2023 ESMO annual meeting included a session on kidney cancer, featuring a presentation by Dr. Georges Gebrael discussing comparative effectiveness of second line treatment with cabozantinib in patients with metastatic clear cell RCC after first line treatment with ipilimumab + nivolumab versus PD-1/L1 inhibitor + TKI. Based on the NCCN guidelines, the preferred first line treatment for patients with metastatic clear cell RCC is either ipilimumab + nivolumab or PD inhibitor + TKI. However, cabozantinib was approved based on phase 3 METEOR trial1 results from patients after prior metastatic clear cell RCC progression on 1-2 TKIs but not PD inhibitor treatment. In the real world, cabozantinib is the most used second line therapy but its effectiveness after prior PD inhibitor based combination is unknown.
The de-identified nationwide, US based, Flatiron Health EHR-derived database was used for this study. Inclusion criteria included diagnosis of metastatic clear cell RCC, first line treatment with ipilimumab + nivolumab or PD inhibitor +TKI (from October 2017 to July 2022) followed by second line treatment with single-agent cabozantinib. Exclusion criteria included first line treatment with cabozantinib, patients with no documentation of first line treatment, or patients with no evidence of contact for 90 days from diagnosis of metastatic clear cell RCC at the treating institution to ensure patients were actively engaged in care at the data providing institution. Time to next therapy, measured from second line to third line, and overall survival (OS; measured from second line) were summarized via Kaplan-Meier survival estimates with 95% CI and compared in the context of propensity score matching weighted analysis and Cox proportional hazard model. The propensity score model included baseline covariates: age, race, smoking status, practice type, insurance, year of first line, IMDC risk factors (all six), and missing covariates.
Among 12,285 patients in the dataset, 237 patients met eligibility, 145 patients received ipilimumab + nivolumab and 92 patients received PD inhibitor + TKI in the first line setting followed by cabozantinib. The baseline characteristics of the study population by treatment arm included some imbalances between groups by their age, race, practice type, insurance, first line therapy year of start, baseline anemia, performance status, initial treatment start, and IMDC risk group:
After the propensity score matching weighting, all the potential confounders achieved adequate balance (SMD <0.1). The median time to next therapy with cabozantinib was 8 months (95% CI 6.9 – 11) for patients treated with ipilimumab + nivolumab and 7.5 months (95% CI 6.3 – 16) for patients treated with PD inhibitor + TKI. Following propensity score matching weighted analysis, there was no significant difference in time to next therapy based on the treatment received in the first line setting (HR 1.43, 95% CI 0.98 – 2.11):
The median OS for cabozantinib from the start of second line therapy was 26 months (95% CI 21 – 32) for patients treated with ipilimumab + nivolumab and 34 months (95% CI 27 – NR) for patients treated with PD inhibitor + TKI. Following propensity score matching weighted analysis, there was no significant difference in OS based on the treatment received in the first line setting (HR 1.16, 95% CI 0.73 – 1.83):
Dr. Gebrael concluded his presentation by discussing comparative effectiveness of second line treatment with cabozantinib in patients with metastatic clear cell renal cell carcinoma after first line treatment with ipilimumab + nivolumab versus PD-1/L1 inhibitor + TKI with the following concluding statements:
- For patients with metastatic clear cell RCC receiving second line cabozantinib, survival outcomes were similar in patients regardless of prior first line treatment with ipilimumab + nivolumab or PD inhibitor + TKI
- Upon external validation, these results may aid with counseling of patients, prognostication, treatment decisions in the clinic, and design of future trials
Presented by: Georges Gebrael, MD, University of Utah, Salt Lake City, UT
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
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