J Cancer 2019; 10(24):6114-6123. doi:10.7150/jca.32638

Research Paper

Indirect comparison between immune checkpoint inhibitors and targeted therapies for the treatment of melanoma

Minliang Wu1*, Yuchong Wang1*, Yalong Xu2*, Ji Zhu1, Chuan Lv1, Mengyan Sun1, Rui Guo1, Yu Xia1, Wei Zhang2✉, Chunyu Xue1✉

1. Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
2. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
* These authors contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wu M, Wang Y, Xu Y, Zhu J, Lv C, Sun M, Guo R, Xia Y, Zhang W, Xue C. Indirect comparison between immune checkpoint inhibitors and targeted therapies for the treatment of melanoma. J Cancer 2019; 10(24):6114-6123. doi:10.7150/jca.32638. Available from http://www.jcancer.org/v10p6114.htm

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Abstract

Background: This systematic review and meta-analysis aims to provide comparative and quantitative data about immune checkpoint inhibitor (IMM) and targeted therapy (TAR) in this work.

Methods: A literature search was performed with PubMed, Embase, PMC database, and Web of Science databases to identify relevant studies. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (ORs) for overall response rate (ORR) were estimated.

Results: Eighteen manuscripts were ultimately utilized for indirect comparisons. In general, both TAR and IMM can prolong the PFS either by monotherapy, combination therapy with chemotherapy or adjuvant therapy. BRAF inhibitor monotherapy showed superiority over anti-CTLA-4 in OS (HR: 1.28, 95%CI: 0.93-1.75) and best ORR (OR: 12.57, 95%CI: 6.63-23.82), as well as longer PFS (HR: 1.63, 95%CI: 1.00-2.67) and higher best ORR (OR: 3.29, 95%CI: 1.94-5.55) compared with anti-PD-1. However, MEK inhibitor monotherapy showed no priority. When combined with chemotherapy, anti-CTLA-4 showed marginally advantages over MEK inhibitor in OS (HR: 0.68, 95%CI: 0.44-1.03), however no advantage in PFS (HR: 1.12, 95%CI: 0.76-1.64), or ORR (OR: 1.78, 95%CI: 0.70-4.49). For post-operational melanoma patient, adjuvant TAR and adjuvant IMM showed no difference in OS (HR: 1.14, 95%CI: 0.82-1.58) or PFS (HR: 1.20, 95%CI: 0.79-1.83). Moreover, the high-rate adverse events and underlying diseases should be considered during the application of those agents.

Conclusions: For the unresectable late-stage melanoma, IMM may be a better choice for the combined treatment with chemotherapy. If the chemotherapy is not tolerable for patients, BRAFi involved TAR can be considered.

Keywords: melanoma, indirect comparison, targeted therapy, immune checkpoint inhibitor