SUO 2017: Immunotherapy of Genitourinary Cancer: Renal Cell Carcinoma – Emerging Data for Locally Advanced and Metastatic Disease

Washington, DC (UroToday.com) Dr. McDermott discussed the index publication of PD1 blockade (nivolumab) compared to mTOR inhibition (everolimus) in metastatic RCC patients previously treated with VEGF or TKI therapy.  However, this brought up translational research questions of improving patient selection and resistance patterns through combination therapy.  Tumors, Dr. McDermott stated, use complex mechanisms to evade and suppress immune response including inhibition of tumor antigen presentation, secretion of immunosuppressive factors, inactivation of T cells, and recruitment of immunosuppressive cell types.

The IMmotion 150, phase II trial was designed to be hypothesis generating and randomized patients to atezolizumab + bevacizumab, atezolizumab alone, or sunitinib.  Patients treated with combination therapy had an improvement in progression free survival who had high PD-L1 expression.

Next gen assays may enhance future biomarker development.  Biomarker strategies for atezolizumab + bevacizumab trials have the goals of enable selection/stratification and registration based on PD-L1 biomarkers, and to identify predictive biomarkers of response, pseudo-progression, progression or resistance.  Atezolizumab + bevacizumab demonstrated improved progression free survival vs sunitinib in the T effector (high) subset.  Additionally, the addition of bevacizumab to atezolizumab was associated with improved benefit in T effector (high) myeloid inflammation (high) subgroup.  Enrollment in ongoing clinical trials will help elucidate this information, whether that be pre- or post-surgical randomization

The S-TRAC study randomized 615 patients to adjuvant sunitinib vs placebo following nephrectomy for patients with high risk RCC with a primary endpoint of disease free survival.  This trial demonstrated an improvement in disease free survival but not overall survival.  Subsequently, the FDA approved sunitinib for adjuvant therapy in high risk patients in November of 2017.  Dr. McDermott questioned the use of TKIs at this point and raised the idea of better adjuvant therapies in this population.

In summary, conflicting data exists from the ASSURE and S-TRAC trials, but the net result favors observation, especially considering PROTECT data.  Review of EAU guideline statement suggest that both patients and physicians want more from current adjuvant therapy than the modest disease-free survival benefit.  Ongoing clinical trials examining adjuvant immunotherapy may improve these outcomes.  While we wait for these results, a push to enroll eligible patients into these trials will strengthen our current knowledge base.

Presented by: David McDermott, MD, Dana-Farber/Harvard Cancer Center, Boston, MA

Written by: David B. Cahn, DO, MBS, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @dbcahn at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC
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