(UroToday.com) In the Indian Urology Symposium held in conjunction with this year’s virtual Société Internationale d'Urologie (SIU) annual congress, Dr. Sudhir Rawal discussed the role of systemic therapy in patients with metastatic renal cell carcinoma (mRCC).
He began by highlighting the most recent National Comprehensive Cancer Network (NCCN) guidelines for the management of advanced kidney cancer which, across risk groups, centers heavily on combination therapies with immune checkpoint inhibitors in both the first and second-line setting.
He highlighted recent reports of the CheckMate214, KEYNOTE-426, IMmotion151, and JAVELIN RENAL 101 trials as well as a subsequent meta-analysis which pooled results suggesting a group level effect.
Further, while these trials focused on patients with clear cell histology, pooled analysis has also demonstrated a benefit to immunotherapy approaches in patients with sarcomatoid RCC and there is promising data supporting this approach in patients with non-clear cell RCC.
He then examined individuals trials, beginning with CheckMate214 comparing the combination of nivolumab and ipilimumab to sunitinib. Among patients in the ITT analysis, overall survival was improved with the combination therapy approach with a greater benefit among those in the intermediate/poor risk subgroup. Interestingly, Dr. Rawal highlighted that the combination immunotherapy approach was associated with significantly higher rates of complete response, some of which were prolonged, even following the cessation of therapy.
Dr. Rawal then discussed three trials comparing the combination of immune checkpoint inhibitors with VEGF targeting agents. Beginning with IMmotion151, he highlighted that, while progression-free survival was improved in the PD-L1 positive cohort, the trial failed to meet the overall survival endpoint and thus did not receive regulatory approval. Combinations of axitinib with avelumab (JAVELIN Renal 101) similarly demonstrated improvements in PFS and overall survival without significant differences in objective response rates. Combination therapy of axitinib with pembrolizumab (KEYNOTE-426) demonstrated improved overall survival, though this benefit was not significant in the favorable risk subgroup.
Dr. Rawal then considered which approach (IO/IO or IO/TKI) should be considered better, highlighting data from CheckMate214 and KEYNOTE-426. Certainly, there is an earlier separation of the curves with the IO/TKI combination but longer-term outcomes (plateau) may favor the IO/IO combination.
He then compared pros/cons of these approaches, concluding that the balance didn’t strongly favor one over the other in most circumstances.
He briefly discussed a number of biomarkers including PD-L1, tumor mutational burden, NLR, PBRM1, and others. However, most of these have not been validated or routinely used. However, patient characteristics including comorbidities may at times steer you away from a specific treatment regime.
Presented by: Sudhir Rawal, MBBS, MS, M.Ch., DNB, Director Surgical Oncology, Chief of Uro-Genito Oncology Rajiv Gandhi Cancer Institute & Research Centre, Delhi, India
Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center, Contact: @WallisCJD on Twitter at the 2020 Société Internationale d'Urologie Virtual Congress (#SIU2020), October 10th - October 11th, 2020
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