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Real-world, population-based cohort study of toxicity and resource utilization of second-line ipilimumab for metastatic melanoma in Ontario, Canada

Dai WF, Beca J, Croxford R, Isaranuwatchai W, Menjak IB, Petrella TM, Mittmann N, Earle CC, Gavura S, Mercer RE, Hanna TP, Chan KKW. Int J Cancer. 2020; Oct 26 [Epub ahead of print]. DOI:

Second-line ipilimumab has been publicly funded in Ontario for metastatic melanoma (MM) since September 2012. We examined real-world toxicity of second-line ipilimumab compared to standard second-line treatments prior to funding. MM patients who received systemic treatment from April 2005 to March 2015 were included. Patients receiving second-line ipilimumab after September 2012 were considered as cases, and those who received second-line treatment prior to the funding date were included as historical controls. Outcomes assessed include treatment-related mortality, any-cause hospital visits, ipilimumab-related hospital visits, and specialist visits (e.g. endocrinologists, ophthalmologists, gastroenterologists, rheumatologists, and respirologists), which were captured from up to 30 and/or 90 days after end of second-line treatment. Inverse probability of treatment weighting was used to adjust for baseline differences between groups. Odds ratios (ORs) from logistic regressions and rate ratios (RRs) from rate regressions were used to assess differences between groups. We identified 329 MM patients who received second-line treatments (ipilimumab: 189; controls: 140). Ipilimumab was associated greater any-cause (60.1% vs 45.7%; OR = 1.81; p-value=0.019;) and ipilimumab-related (47.2% vs 31.9%; OR = 1.91; p-value=0.011;) hospital visits. Adjusting for different follow-up days, ipilimumab was associated with higher rates of all-cause (RR=1.56 [95%CI: 1.12 - 2.16]), and ipilimumab-related (RR=2.18 [95%CI: 1.45 - 3.27]) hospital visits. Patients receiving ipilimumab were more likely to visit specialist involved in immunotherapy toxicity management (23.5% vs 13.7%; p-value=0.04). Compared to historical second-line treatments, second-line ipilimumab was associated with more health service utilization (specifically hospital visits and specialist visits), suggestive of potentially increased toxicity in the real-world.