Kidney Cancer Journal 53 ASCO 2017 Meeting Report Combination Therapies Dominate the Agenda of the Worldwide Meeting he world of oncology once again convened in Chicago for our annual gathering aimed at conquering cancer and celebrating new developments, which are coming ever faster and more furious. Although once considered almost taboo in RCC, many of the most intriguing presentations and abstracts from the American Society of Clinical Oncology’s (ASCO) annual meeting focused on various combination therapies in RCC, especially combinations invol- ving immunotherapies. Highlights From Combination Studies Epacadostat and pembrolizumab. The preliminary results of the phase I/II ECHO-202/KEYNOTE-037 study that paired epacadostat with pembrolizumab were quite promising. The phase I portion of the study did not identity a maximum tolerated dose as the combination was relatively well tolerated at all dose levels. The expansion cohort analyzed 19 patients who had received no prior treatment or one prior treatment; in this population, the overall response rate (ORR) and disease control rate (ORR + stable disease) were 47% and 58%, respectively. There were no responses in patients who had received two or more prior therapies, but a stable disease rate of 36% was achieved. 15% of patients experienced grade 3 or higher adverse events, and 2 subjected discontinued treatment due to toxicity.1 Avelumab and Axitinib. Another combination study that garnered a lot of attention at the meeting was a phase 1b trial that paired avelumab + axitinib for the first-line treatment of advanced RCC. 55 treatment-naïve patients with advanced RCC were treated with the combination. ORR was impressive at 54.5%, including 2 complete responses, toxicity was a concern, but seemed managable for most patients with 52 patients reporting axitinib-related adverse events (including frequent fatigue, diarrhea, hypertension, and dysphonia) and 51 of subjects reporting avelumab-related toxicities (including most frequently, diarrhea and fatigue). Four patients discontinued axitinib and five patients discontinued avelumab due to toxicities. The results certainly warrant further study of this combination.2 Cabozantinib and nivolumab. One of the most interesting combinations reported came from an small, early trial that evaluated the safety and clinical activity of the combination of cabozantinib and nivolumab as well as the triple combination of cabozantinib, nivolumab, and ipilumumab in patients with patients with a variety of genitourinary cancer patients, including two patients with conventional RCC and two patients with sarcomatoid dedifferentiation. Both combinations were surprisingly relatively well tolerated with no dose limiting toxicities noted. One of the patients with sarcomatoid dedifferentiation was noted to have a partial response, and responses were also seen in patients with other rare genitourinary malignancies including squamous cell carcinoma of the bladder, urachal, and penile cancers. Larger cohorts of testing the combination in bladder cancers and rare genitourinary tumors are ongoing.3 Atezolizumab and bevacizumab. The IMmotion150 study, another interesting phase II combination trial paired the checkpoint inhibitor atezolizumab with bevacizumab in the first-line setting in patients with previously untreated metastatic RCC and compared this to too other arms, one using only single agent atezolizumab and the other single agent sunitinib. Both comparator arms had the option of crossing over to the combination therapy at progression. In the 54% of PD-L1–positive patients, the median PFS was 14.7 months with the combination, 5.5 months with atezolizumab alone, and 7.8 months in sunitinib alone arm. 60% of patients receiving atezolizumab alone went on to receive the combination and demonstrated a 24% response rate, while 78% of patients Marc R. Matrana, MD, MS, FACP Medical Director, Precision Cancer Therapies (Phase 1) Program, Ochsner Cancer Institute, New Orleans, Louisiana Senior Lecturer, Ochsner Clinical School, University of Queensland, New Orleans, Louisiana and Brisbane, QLD, Australia. Erin Pierce, MSN, APRN, FNP-C Advanced Practitioner, Genitourinary Medical Oncology and Phase I Research, Ochsner Cancer Institute, New Orleans, Louisiana Lorrie Erario, RN, OCN Nurse Supervisor, Hematology and Medical Oncology Clinics, Ochsner Cancer Institute, New Orleans, Louisiana T
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