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. 2020 Mar;25(3):e536-e544.
doi: 10.1634/theoncologist.2019-0550. Epub 2019 Nov 7.

Association Between Skin Reaction and Clinical Benefit in Patients Treated with Anti-Programmed Cell Death 1 Monotherapy for Advanced Non-Small Cell Lung Cancer

Mari Aso  1 , Yukihiro Toi  1 , Jun Sugisaka  1 , Tomoiki Aiba  1 , Sachiko Kawana  1 , Ryohei Saito  1 , Takahiro Ogasawara  1 , Kyoji Tsurumi  1 , Kana Ono  1 , Hisashi Shimizu  1 , Yutaka Domeki  1 , Keisuke Terayama  1 , Yosuke Kawashima  1 , Atsushi Nakamura  1 , Shinsuke Yamanda  1 , Yuichiro Kimura  1 , Yoshihiro Honda  1 , Shunichi Sugawara  1
Affiliations

Association Between Skin Reaction and Clinical Benefit in Patients Treated with Anti-Programmed Cell Death 1 Monotherapy for Advanced Non-Small Cell Lung Cancer

Mari Aso et al. Oncologist. 2020 Mar.

Abstract

Background: Anti-programmed cell death 1 antibody is a standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs), such as skin reactions, are frequently observed. Although skin reactions are associated with clinical efficacy in melanoma, this association in advanced NSCLC and predictors of irAEs remain unclear. Accordingly, this study identified potential correlations of skin reactions with clinical efficacy and clinical predictors of development of skin reactions.

Subjects, materials, and methods: We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n = 155) during January 2016 to April 2018. Treatment efficacy was evaluated in patients with and without skin reactions, and associated predictive markers were determined. A 6-week landmark analysis was conducted to assess the clinical benefit of early skin reactions.

Results: Skin reactions were observed in 51 patients with a median time to onset of 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions (57% vs. 19%, p < .001). Median progression-free survival (PFS) durations of 12.9 and 3.5 months and overall survival durations of not reached and 11.4 months were observed in patients with and without skin reactions, respectively. In the 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions, and skin reactions were significantly associated with increased PFS. A multivariate analysis identified pre-existing rheumatoid factor (RF) as an independent predictor of skin reactions.

Conclusion: Skin reactions appeared beneficial in patients treated with nivolumab/pembrolizumab for advanced NSCLC and could be predicted by pre-existing RF. Further large-scale validations studies are warranted.

Implications for practice: This single-institutional medical record review that included 155 patients with advanced non-small cell lung cancer who were treated with nivolumab or pembrolizumab monotherapy revealed that overall response rate and progression-free survival were significantly better in patients with skin reactions. Pre-existing rheumatoid factor was an independent predictor of skin reactions.

Keywords: Immune-related adverse events; Immunotherapy; Lung cancer; Programmed cell death 1; Rheumatoid factor; Skin reaction.

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Conflict of interest statement

Disclosures of potential conflicts of interest may be found at the end of this article.

Figures

Figure 1
Figure 1
Progression‐free survival and overall survival in patients with or without skin reactions. Kaplan‐Meier curves are shown for progression‐free survival (A) and overall survival (B) in patients with or without skin reaction. The red line indicates patients with skin reaction; the black line represents those without skin reaction. Ticks indicate patients for whom data were censored on October 19, 2018. Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached.
Figure 2
Figure 2
Progression‐free survival in patients with or without skin reactions in 6 weeks. Kaplan‐Meier curves with 6‐week landmark analysis for progression‐free survival in patients with or without skin reactions. The red line indicates patients with skin reaction; the black line represents those without skin reaction. Ticks indicate patients for whom data were censored on October 19, 2018. Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached.
See this image and copyright information in PMC

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