Ipilimumab and nivolumab (I+N) as first-line treatment of metastatic renal cell carcinoma (mRCC): A real-world review in North West of England, United Kingdom.
Authors: Jennifer Allison, Richard Griffiths, Tom Waddell, Manon Rhys Pillai
Journal: Journal of Clinical Oncology (2021)

295 Background: Ipilimumab and Nivolumab (I+N) is now an established first line option for patients with advanced RCC of intermediate (I) or poor (P) IMDC risk score. In this retrospective review, we review our experience of this combination in two cancer centres in North West England with a focus on immune related adverse events (irAEs) and their impact on the patient pathway. Methods: Treatment naïve mRCC patients starting I+N between May 2019 and July 2020 were identified. Primary outcomes of interest include overall response rate (ORR), the management of irAEs and early survival observations. Results: A total of 69 patients were identified. Median age was 60yr (19-82yr), 77% had clear cell histology. The IMDC risk was 72% I and 28% P. Median follow-up was 11.0 mo (1-22mo). ORR was 45% (CR 9%, PR 36%, SD 28%, PD 23%, NE 4%) Median time to first response was 2.9mo. (1.8- 15.5mo). 10% of patients experienced pseudoprogression. Median PFS and OS are not yet reached with 86% of patients still alive at the time of data cut-off. The majority (75%) of patients completed all 4 doses of I+N. Of the 10% receiving less than 4 doses due to toxicity, 14% continued on single agent N. Overall, 15% discontinued therapy due to toxicity and 28% experienced at least one treatment delay. Any grade irAEs were seen in 74% of patients (G3 35%) with no treatment related deaths. The commonest irAEs were: rash/pruritis 39%; endocrinopathies 30%(G3 7%); diarrhoea 29% (G3 14%); hepatitis 22% (G3 6%); and nephritis 3% (G3 3%). Of the patients developing irAEs, 71% received steroids with 16% requiring additional immunosuppression including infliximab (6%) and mycophenolate mofetil (8%). A third of all patients required admission for irAE management with a total of 37 inpatient episodes across the cohort with a median length of 7 days (1-24). 7% of patients proceeded to surgery for either primary or metastatic disease, which contributed to ongoing disease response in these patients. At the time of data cut-off, 45% of patients were no longer on treatment due to PD (29%), toxicity (15%) or unrelated death (1%). Of those who stopped due to toxicity, 50% subsequently progressed with a median time to progression of 4mo (3-6 mo) and 50% remain on active surveillance with a median follow-up of 7.5mo (1-10). 62% of patients with PD received second line treatment; most frequently, cabozantinib (83%). Conclusions: Our experience of I+N shows comparable efficacy and toxicity profiles to available reports. irAEs requiring intervention are frequent and may be associated with prolonged hospital admission, and patients should be counselled appropriately. Data within mirrors published reports of ongoing responses in a subset of patients who stop treatment due to toxicity and also suggests a possible role for resection of residual or metastatic disease in disease control. Updated survival data will be presented.