Targeting immune checkpoints in unresectable metastatic cutaneous melanoma: a systematic review and meta-analysis of anti-CTLA-4 and anti-PD-1 agents trials

Seongseok Yun, Nicole D. Vincelette, Myke R. Green, Andrea E. Wahner Hendrickson, Ivo L Abraham

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) inhibitors have been shown to significantly improve survival in patients with metastatic cutaneous melanoma. However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta-analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti-CTLA-4 or anti-PD-1 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma. Progression-free survival (PFS) rate at 6 months was 28.5% versus 17.7% (RR: 0.84, 95% CI: 0.76–0.93), overall survival (OS) rate at 1 year was 51.2% versus 38.8% (RR: 0.72, 95% CI: 0.59–0.88), and overall response rate (ORR) at 6 months was 29.6% versus 17.7% (RR: 0.85, 95% CI: 0.76–0.95) favoring immune check point inhibitors over chemotherapies or vaccination. Immune check point inhibitors were associated with more frequent immune-related adverse events at 13.7% versus 2.4% of treated patients (RR: 6.74, 95% CI: 4.65–9.75). Subgroup analyses demonstrated significant PFS (RR: 0.92 vs. 0.74, P < 0.00001) and ORR (RR: 0.95 vs. 0.76, P = 0.0004) improvement with anti-PD-1 treatment compared to anti-CTLA-4 when each of them was compared to control treatments. Collectively, these results demonstrate that immune checkpoint inhibitors have superior outcomes compared to conventional chemotherapies or vaccination, and support the results of recent randomized trials that showed superior outcomes with anti-PD-1 agents over ipilimumab in unresectable metastatic cutaneous melanoma patients.

Original languageEnglish (US)
Pages (from-to)1481-1491
Number of pages11
JournalCancer Medicine
Volume5
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

CTLA-4 Antigen
Meta-Analysis
Melanoma
Cell Death
Skin
Vaccination
Drug Therapy
Disease-Free Survival
Survival Rate
Therapeutics
Randomized Controlled Trials
Safety
Survival
Thomsen-Friedenreich antibodies

Keywords

  • CTLA-4
  • Ipilimumab
  • Lambrolizumab
  • metastatic melanoma
  • nivolumab
  • PD-1
  • pembrolizumab
  • tremelimumab

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Targeting immune checkpoints in unresectable metastatic cutaneous melanoma : a systematic review and meta-analysis of anti-CTLA-4 and anti-PD-1 agents trials. / Yun, Seongseok; Vincelette, Nicole D.; Green, Myke R.; Wahner Hendrickson, Andrea E.; Abraham, Ivo L.

In: Cancer Medicine, Vol. 5, No. 7, 01.07.2016, p. 1481-1491.

Research output: Contribution to journalArticle

Yun, Seongseok ; Vincelette, Nicole D. ; Green, Myke R. ; Wahner Hendrickson, Andrea E. ; Abraham, Ivo L. / Targeting immune checkpoints in unresectable metastatic cutaneous melanoma : a systematic review and meta-analysis of anti-CTLA-4 and anti-PD-1 agents trials. In: Cancer Medicine. 2016 ; Vol. 5, No. 7. pp. 1481-1491.
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abstract = "Anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and anti-programmed cell death-1 (PD-1) inhibitors have been shown to significantly improve survival in patients with metastatic cutaneous melanoma. However, there was some heterogeneity as well as some variation in the degree of benefit across studies. We reviewed randomized trials and performed a meta-analysis to determine the efficacy and safety of immune checkpoint inhibitors in comparison with conventional regimens. Eligible studies were limited to randomized controlled trials comparing anti-CTLA-4 or anti-PD-1 inhibitors to chemotherapy or vaccination treatment in adult patients with unresectable cutaneous metastatic melanoma. Progression-free survival (PFS) rate at 6 months was 28.5{\%} versus 17.7{\%} (RR: 0.84, 95{\%} CI: 0.76–0.93), overall survival (OS) rate at 1 year was 51.2{\%} versus 38.8{\%} (RR: 0.72, 95{\%} CI: 0.59–0.88), and overall response rate (ORR) at 6 months was 29.6{\%} versus 17.7{\%} (RR: 0.85, 95{\%} CI: 0.76–0.95) favoring immune check point inhibitors over chemotherapies or vaccination. Immune check point inhibitors were associated with more frequent immune-related adverse events at 13.7{\%} versus 2.4{\%} of treated patients (RR: 6.74, 95{\%} CI: 4.65–9.75). Subgroup analyses demonstrated significant PFS (RR: 0.92 vs. 0.74, P < 0.00001) and ORR (RR: 0.95 vs. 0.76, P = 0.0004) improvement with anti-PD-1 treatment compared to anti-CTLA-4 when each of them was compared to control treatments. Collectively, these results demonstrate that immune checkpoint inhibitors have superior outcomes compared to conventional chemotherapies or vaccination, and support the results of recent randomized trials that showed superior outcomes with anti-PD-1 agents over ipilimumab in unresectable metastatic cutaneous melanoma patients.",
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