Comparative efficacy of dabrafenib + trametinib versus treatment options for metastatic melanoma in first-line settings.

Aim: The objective was to systematically review the literature and assess the relative efficacy of agents approved in first-line settings via network meta-analysis. Materials & methods: A literature review was conducted via searching different medical databases. The eligibility criteria included Phase II or III randomized controlled trials that had enrolled treatment-naive adult patients with advanced/metastatic melanoma. Results: The network meta-analysis results suggested that dabrafenib + trametinib significantly prolongs the survival outcomes compared with the monotherapies and had comparable efficacy profile compared with encorafenib + binimetinib and cobimetinib + vemurafenib. In comparison with immunotherapies, the results varied for progression-free survival and overall survival. Conclusion: Long-term survival data of dabrafenib + trametinib establishes the combination as one of the preferred treatment options for previously untreated melanoma patients.

An updated cost-effectiveness analysis of pazopanib versus sunitinib as first-line treatment for locally advanced or metastatic renal cell carcinoma in Italy.

OBJECTIVE: To assess the cost-effectiveness of pazopanib versus sunitinib as a first-line treatment for patients with metastatic renal cell carcinoma (mRCC) from an Italian National Health Service perspective, considering the evolving Italian landscape in terms of new reimbursement agreements trend. METHODS: This analysis is an update of the previously published cost-effectiveness analysis to incorporate recent 2019 costs and additional changes regarding drug discounting. A partitioned-survival analysis model with three different health states (progression-free survival, post-progression survival, and dead) was utilized. Outcomes included progression-free life years, post-progression life years, overall life years, quality-adjusted life years (QALYs), and costs calculated for both treatments. Cost-effectiveness was assessed in terms of incremental costs per QALY gained and the net monetary benefit (NMB) of pazopanib versus sunitinib. In the base case analysis, a time horizon of 5 years was used and future costs and QALYs were discounted at a 3% annual discount rate. An impact of methodological and parameter uncertainly on base case results was evaluated using probabilistic and deterministic sensitivity analyses. RESULTS: In the base case, pazopanib had higher QALYs (+0.060) at lower costs (-€5,857) versus sunitinib, hence it dominated sunitinib. At willingness-to-pay thresholds of €30,000 and €50,000 per QALY, the NMB with pazopanib were €7,647 and €8,841 per patient, respectively, versus sunitinib. The probability that pazopanib is cost-effective versus sunitinib was estimated to be 97.5% at a cost-effectiveness threshold of €20,000, 95.4% at a threshold of €30,000, and 90.2% at a threshold of €50,000 per QALY. Cost-effectiveness results were robust to changes in key parameter values and assumptions as demonstrated by deterministic sensitivity analyses. CONCLUSIONS: Pazopanib is likely to represent a cost-effective treatment option compared with sunitinib as a first-line treatment for patients with metastatic RCC in Italy.

Real-world Clinical Outcomes of Pazopanib Immediately After Discontinuation of Immunotherapy for Advanced Renal Cell Carcinoma.

INTRODUCTION: In the first-line (1L) setting, pazopanib (PAZ) has been recommended by the National Comprehensive Cancer Network for the treatment of advanced renal cell carcinoma (aRCC). In 2018, immuno-oncology (IO) therapy became a commonly used 1L treatment option for aRCC. We report the real-world clinical outcomes of PAZ after IO therapy for patients with aRCC. MATERIALS AND METHODS: We performed a longitudinal, retrospective medical record review study. The included patients were aged ≥ 18 years, had initiated second-line and/or beyond PAZ after IO therapy for clear cell aRCC on or before October 2017, and had complete medical records available from the diagnosis of aRCC to the discontinuation of PAZ, death, or the medical record extraction date (May 2018), whichever occurred first. The primary outcome variable was the PAZ duration of therapy. The secondary outcomes were progression-free survival and overall survival since PAZ initiation, the reasons for PAZ discontinuation, and the occurrence of adverse events (AEs). RESULTS: A total of 258 eligible patients had initiated IO therapies before PAZ as follows: nivolumab (68%), nivolumab plus ipilimumab (14%), pembrolizumab (12%), and ipilimumab (3%). Overall, the median PAZ duration of therapy was 13.4 months (95% confidence interval [CI], 10.1-16.0 months). The median progression-free survival with PAZ after IO therapy was 13.5 months (95% CI, 11.8 months to not reached). The estimated overall survival rate of PAZ after IO therapy at 6 and 12 months was 93% and 89%, respectively. A total of 109 patients (42%) had reported an AE. The most frequently reported AEs were fatigue (29%) and diarrhea (14%). No additional safety signal of hepatotoxicity was observed (increased aspartate aminotransferase, 5%; increased alanine transaminase, 6%). CONCLUSIONS: In the present real-world study, second-line and/or beyond PAZ after previous IO therapy was well-tolerated and effective for patients with aRCC.

Real-World Effectiveness and Tolerability of Pazopanib as First Targeted Therapy in Metastatic Renal Cell Carcinoma: A Retrospective Chart Review in Latin America.

INTRODUCTION: Pazopanib is approved in Latin America as first targeted therapy for patients with metastatic renal cell carcinoma (mRCC). METHODS: A retrospective chart review of adult patients with mRCC who initiated pazopanib as first targeted therapy between January 2011 and March 2016 was conducted among oncology care centers in Argentina, Brazil, Chile, Colombia, and Mexico. Patient characteristics, treatment patterns, overall survival (OS), progression-free survival (PFS), and adverse events were summarized. RESULTS: A total of 156 charts of patients with mRCC receiving first-line pazopanib were reviewed (29, 54, 27, 28, and 18 patients from Argentina, Brazil, Chile, Colombia, and Mexico, respectively). The mean age at initial mRCC diagnosis was 61.6 years, 73.7% were male, and 51.3% were Hispanic. The median dose of pazopanib was 800 mg and the median time from initial mRCC diagnosis to pazopanib start was 2.2 months. The median time on treatment was 10.0 months. At the time of data extraction, 16.7% of patients remained on pazopanib, with clinical progression listed as the main reason for discontinuation. Subsequent therapy was received by 25.6% of patients; the most common were everolimus (9.6%) and axitinib (5.8%). Overall, median PFS and OS were 10.8 and 16.9 months, respectively, and varied across countries. The most common all-grade adverse events were diarrhea (44.9%), asthenia/fatigue (43.6%), and nausea (28.8%). CONCLUSIONS: Pazopanib was used for first-line mRCC treatment in a clinically diverse patient population across Latin America. Real-world PFS and tolerability were similar to clinical studies of pazopanib. FUNDING: Novartis Pharmaceuticals Corporation, Inc.