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

Wei Fang Dai,Wanrudee Isaranawatchai,Timothy P Hanna,Jaclyn M Beca,Teresa M Petrella,Kelvin K.W Chan,Nicole Mittmann,Ruth Croxford,Scott Gavura,Ines B Menjak,Craig C Earle

doi:10.1186/s12885-020-06798-1

Abstract

BackgroundFor 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).MethodsWe 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).ResultsWe 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).ConclusionsThis real-world analysis suggests second-line ipilimumab is associated with an improvement in OS for MM patients in routine practice.

Highlights

For novel cancer treatments, effectiveness in clinical practice is not always aligned with clinical efficacy results
Study population Patients diagnosed with melanoma (International Classification of Disease for Oncology, 3rd edition - topography:C44) who started first-line systemic treatment for advanced melanoma on or after April 1, 2005 were identified from the Activity Level Reporting (ALR) systemic treatment database maintained by the provincial cancer agency, Cancer Care Ontario
Patients who are treated with second-line ipilimumab were older (61.7 years vs 55.2 years) compared to historical controls

Summary

Introduction

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. The treatment effects of novel cancer therapies adopted into clinical practice (effectiveness) do not always align with clinical trial outcomes (efficacy) [1]. Prior to the introduction of ipilimumab, treatment options for MM patients typically include standard cytotoxic chemotherapy such as dacarbazine or temolozomide. Often, these treatments conferred limited benefit with phase II trial results showing median overall survival around 6.2 months and 1 year survival rate of 25.5% [3]. Funding for ipilimumab in Canada was subsequently extended to first-line use in 2015 and to combination therapy with nivolumab in 2019

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Results

Conclusion