Evaluation of efficacy and safety of different pembrolizumab dose/schedules in treatment of non-small-cell lung cancer and melanoma: a systematic review

Abstract

Aim: Pembrolizumab is a fully humanized anti-PD-1 agent currently approved for the treatment of advanced melanoma and pretreated non-small-cell lung cancer (NSCLC). Objective: To assess the efficacy and safety of different dose schedules of pembrolizumab in the treatment of patients with advanced NSCLC and melanoma. Search method: MEDLINE database has been searched. Reference lists of original studies and review articles were checked for other related articles. Selection criteria: Prospective clinical trials reporting the outcomes of more than one dose schedule of pembrolizumab in the treatment of advanced NSCLC and melanoma. Data collection & analysis: The review author extracted information on the outcomes of the study for this review, and presented the results. Main results: Four trials with 3425 patients were included in this systematic review. Pooled analysis for the odds ratio of objective response rate comparing 2 versus 10 mg/kg every 3 weeks in advanced melanoma was 1.03 (95% CI: 0.71–1.49; p = 0.89), while for advanced NSCLC, it was 0.97 (95% CI: 0.66–1.43; p = 0.87). Moreover, odds ratio for selected side effects between the two doses was as follows: rash: 0.83 (95 CI: 0.58–1.18; p = 0.29); vitiligo: 1.27 (95% CI: 0.62–2.61; p = 0.52); diarrhea: 0.94 (95% CI: 0.63–1.42; p = 0.79); hypothyroidism: 0.97 (95% CI: 0.63–1.50; p = 0.90); hepatitis/elevated transaminases: 1.86 (95% CI: 0.91–3.79; p = 0.09); nephritis: 0.88 (95% CI: 0.32–2.44; p = 0.80); pneumonitis: 1.17 (95% CI: 0.62–2.23; p = 0.63). Conclusions: Given the equivalence in efficacy and safety between lower doses and higher doses of pembrolizumab, 2 mg/kg every 3 weeks seems to be an appropriate dose for routine practice in advanced pretreated NSCLC and melanoma.