Real-world comparative effectiveness of second-line ipilimumab for metastatic melanoma: a population-based cohort study in Ontario, Canada.

BACKGROUND: For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results. As such it is important to understand a treatment's real-world effectiveness. We examined real-world population-based comparative effectiveness of second-line ipilimumab versus non-ipilimumab treatments (chemotherapy or targeted treatments). METHODS: We used a cohort of melanoma patients receiving systemic treatment for advanced disease since April 2005 from Ontario, Canada. Patients were identified from provincial drug databases and the Ontario Cancer Registry who received second-line ipilimumab from 2012 to 2015 (treated) or second-line non-ipilimumab treatment prior to 2012 (historical controls). Historical controls were chosen, to permit the most direct comparison to pivotal trial findings. The cohort was linked to administrative databases to identify baseline characteristics and outcomes. Kaplan-Meier curves and multivariable Cox regression models were used to assess overall survival (OS). Observed potential confounders were adjusted for using inverse probability of treatment weighting (IPTW). RESULTS: We identified 329 patients with metastatic melanoma (MM) who had received second-line treatments (189 treated; 140 controls). Patients receiving second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls. Median OS were 6.9 (95% CI: 5.4-8.3) and 4.95 (4.3-6.0) months for ipilimumab and controls, respectively. The crude 1-year, 2-year, and 3-year OS probabilities were 34.3% (27-41%), 20.6% (15-27%), and 15.2% (9.6-21%) for ipilimumab and 17.1% (11-23%), 7.1% (2.9-11%), and 4.7% (1.2-8.2%) for controls. Ipilimumab was associated with improved OS (IPTW HR = 0.62; 95% CI: 0.49-0.78; p < 0.0001). CONCLUSIONS: This real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Are population-based patient-reported outcomes associated with overall survival in patients with advanced pancreatic cancer?

BACKGROUND: Advanced pancreatic cancer (APC) patients often have substantial symptom burden. In Ontario, patients routinely complete the Edmonton Symptom Assessment Scale (ESAS), which screens for nine symptoms (scale: 0-10), in cancer clinics. We explored the association between baseline patient-reported outcomes, via ESAS, and overall survival (OS). METHODS: Advanced pancreatic cancer patients with ESAS records prior to receiving publicly funded drugs from November 2008 to March 2016 were retrospectively identified from Cancer Care Ontario's administrative databases. We examined three composite ESAS scores: total symptom distress score (TSDS: 9 symptoms), physical symptom score (PHS: 6/9 symptoms), and psychological symptom score (PSS: 2/9 symptoms); Composite scores greater than defined thresholds (TSDS ≥36, PHS ≥24, PSS ≥8) were considered as high symptom burden. Crude OS was assessed using Kaplan-Meier method. Hazard ratios (HRs) were assessed using multivariable Cox models. Analysis was repeated in a sub-cohort with Eastern Cooperative Oncology Group (ECOG) status and metastasis. RESULTS: We identified 2199 APC patients (mean age 64 years, 55% male) with ESAS records prior to receiving chemotherapy. Crude median survival was 4.5 and 7.3 months for high and low TSDS, respectively. High TSDS was associated with lower OS (HR = 1.47, 95% CI: 1.33, 1.63). In the sub-cohort (n = 393) with ECOG status and metastasis, high TSDS was also associated with lower OS (HR = 1.34, 95% CI: 1.04, 1.73). Similar trends were observed for PHS and PSS. CONCLUSIONS: Higher burden of patient-reported outcome was associated with reduced OS among APC patients. The effect was prominent after adjusting for ECOG status.