Patients with unifocal cystic renal cell carcinoma evaluated using a standardized radiological threshold of greater than 50% cystic had an excellent prognosis on active surveillance and after surgical resection.
Background: Several phase 3 studies reported positive results for combinations of Immune-Oncology (IO) and Vascular Endothelial Growth Factor (VEGF) targeted therapies in patients with metastatic clear cell Renal Cell Carcinoma (ccRCC). However, there are limited data on outcomes to systemic therapy after IO-VEGF combinations. Methods: A retrospective analysis was performed on patients with metastatic ccRCC treated at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic who initiated systemic therapy post IO-VEGF including combinations with VEGF receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with the anti-VEGF monoclonal antibody bevacizumab (IO-Bev). The study objectives were to evaluate the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) on systemic therapy post IO-VEGF. RECIST v1.1 criteria were used to determine radiological responses and progression. Survival estimates were evaluated with the Kaplan-Meier methods and the log-rank test from the start of systemic therapy post IO-VEGF to the event of interest. Results: A total of fifty-nine patients were treated post discontinuation of IO-VEGF regimens which included IO-Bev (n = 35; 59%) and IO-TKI (n = 24; 41%). Fifty-eight patients (98%) received IO-VEGF regimens as part of a clinical trial. Subsequent therapies included cabozantinib (n = 22; 37%), axitinib (n = 18; 31%), pazopanib (n = 4; 7%), lenvatinib and everolimus (n = 4; 7%), mTOR inhibitor monotherapy (n = 3; 5%), axitinib and dalantercept (n = 2; 3%), sunitinib (n = 1; 2%), sorafenib (n = 1; 2%), and treatment with agents on unreported clinical trials (n = 4; 7%). Patients treated on unreported clinical trials were excluded from the efficacy analysis. Post IO-VEGF, the ORR was 25% and median PFS was 12.0 months (95% CI, 8.2-24.5). Median OS was 24.5 months (95% CI, 12-NE) and 12 months OS rate was 63.3% (95% CI, 48.6-74.9). We observed no differences post IO-VEGF OS when comparing IO-TKI vs IO-Bev (Log-rank p = 0.73). Conclusions: Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF.
Purpose High body mass index (BMI) may lead to improved immune-checkpoint blockade (ICB) outcomes in metastatic clear cell renal cell carcinoma (mccRCC). However, BMI is a crude body size measure. We investigated BMI and radiographically assessed body composition (BC) parameters association with mccRCC ICB outcomes. Patients and methods Retrospective study of ICB treated mccRCC patients. BMI and BC variables (skeletal muscle index (SMI), and multiple adiposity indexes) were determined using pre-treatment CT scans. We examined the associations between BMI and BC variables with ICB outcomes. Therapeutic responses per RECIST V1.1 were determined. We compared whole transcriptomic patterns with BC variables in a separate cohort of 62 primary tumor samples. Results 205 mccRCC patients included in the cohort (74% were male, 71% were overweight/obese, and 53% were classified as low SMI). High BMI patients experienced longer overall survival (OS) than normal weight patients (unadjusted HR 0.66 (95% CI: 0.45-0.97); p=0.035). The only BC variable associated with OS was SMI (unadjusted HR comparing low vs. high SMI 1.65 (95% CI: 1.13-2.43); p=0.009). However, this OS association became non-significant after adjusting for IMDC score and line of therapy. No OS association was seen for adiposity and no BC variable was associated with progression-free survival or radiological responses. Tumors from patients with low SMI displayed increased angiogenic, inflammatory, and myeloid signals. Conclusion Our findings highlight the relevance of skeletal muscle in the BMI paradox. Future studies should investigate if addressing low skeletal muscle in metastatic patients treated with ICB can improve survival.
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