ASCO GU 2018: Optimal Sequencing of First and Second Line Systemic Therapy in Metastatic Clear Cell Renal Cell Carcinoma
In 2015, Choueri et al. published their data comparing cabozantinib versus everolimus in advanced RCC demonstrated a HR of 0.58 (95% CI 0.45-0.75, p<0.001) for progression free survival. Dr. Motzer and colleagues compared nivolumab to everolimus which also demonstrated oncologic superiority.
PD-1 blockade data has demonstrated a relatively safe clinical profile with 54.9% grade 3-4 adverse reactions and only 12.1% discontinuation due to the adverse events. More recently, combination PD-1 and CTLA-4 blockade with nivo and ipi has been compared to sunitinib. Overall survival for the combination therapy was not reached, with 26.4 months for sunitinib (p<0.0001). This likely is the impetus for future combination therapy as first line treatment. Similarly, atezo + bev compared to sunitinib had an improvement in progression free survival (11.2 vs 7.7 months, p=0.02).
Multiple phase 3 trials are evaluating PD-1 based combination therapy in metastatic RCC exist. Most of these use sunitinib as their control arm. The newest question is whether this combination therapy is additive or synergistic. Future studies are needed to elucidate this data. Deep responses have also correlated with durable survival in PD-L1 blockade. Biomarker models are needed to help predict responses.
Rational applications of sequential treatment in RCC is needed to develop optimal protocols.
Presented by: David McDermott, MD, Dana Farber/Harvard Cancer Center
Written by: David B. Cahn, DO, MBS @dbcahn, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10, 2018 - San Francisco, CA