Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events

Anna Jokimäki, Henna Hietala, Jasmiini Lemma, Hanna Karhapää, Anna Rintala, Jari Pekka Kaikkonen, Kaisa Sunela, Eva Boman, Arja Jukkola, Satu Tiainen, Jan Seppälä, Aino Rönkä, Heikki Hakkarainen, Aarno Kärnä, Sanna Iivanainen, Jussi Koivunen, Päivi Auvinen, Micaela Hernberg, Milla Kuusisto, Tuomas SelanderOuti Kuittinen

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Abstract

Background: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. Methods: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Results: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively). Conclusions: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.

Original languageEnglish
Pages (from-to)3337–3347
JournalCancer Immunology, Immunotherapy
Volume72
Issue number10
Early online date2023
DOIs
Publication statusPublished - 2023
Publication typeA1 Journal article-refereed

Keywords

  • Immune checkpoint inhibitors
  • Immune-related adverse events
  • Overall response rate
  • Radiotherapy

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology
  • Cancer Research

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