Systemic effect of radiotherapy before or after nivolumab in lung cancer: an observational, retrospective, multicenter study

Abstract

Background: The combination of radiotherapy (RT) and programmed death 1 inhibitors seems to increase antitumor immune responses. Objective: To assess the outcome and the role of the best combination sequence, i.e. immunotherapy given before, during, and/or after RT, in patients with non-small cell lung cancer (NSCLC). Methods: We conducted an observational, retrospective analysis of 95 consecutive patients with advanced NSCLC who received any radiotherapy treatment and nivolumab, as clinically indicated. Median overall survival (OS) and the 95% confidence interval (CI) were estimated with the Kaplan-Meier method. Cox model was used to obtain hazard ratio (HR) and associated 95% CI with statistical inference by log-rank statistic. Results: Median OS was 11.9 months (95% CI, 6.6–17.2). Patients who received radiotherapy during an immune checkpoint inhibitor treatment started more than 60 days before showed a better outcome than patients who started immunotherapy over 60 days after RT ending (HR, 2.90 [1.37–6.12], p = 0.005; median OS, 22.4 months vs 8.6 months, p = 0.005). Median progression-free survival was 6.3 months (95% CI, 4.6–8.0). Conclusions: This study shows that combining irradiation with nivolumab for the treatment of advanced NSCLC leads to improved OS. The optimal time window for the combination of RT and immunotherapy seems to play a critical role for therapeutic antitumor response derived by abscopal effect.

Clinical evidence for synergy between immunotherapy and radiotherapy (SITAR)

“…A non-randomised retrospective analysis of 95 consecutive patients with advanced NSCLC who received radiation therapy treatment either during or within 60 days of nivolumab showed a median overall survival (OS) of 22.4 months vs 8.6 months. 45 The definition of radiation therapy within 60 days after immunotherapy as concurrent was used because of the long half-life of nivolumab, a feature common to immune checkpoint inhibitors. A subgroup analysis of the KEYNOTE-001 trial showed that OS after pembrolizumab was significantly longer in patients who had received previous radiation therapy than in those who were radiation therapy na€ ıve (HR 0.58 P = 0.026; OS 10.7 months vs 5.3 months).…”

“…Two further retrospective studies support SITAR. A non‐randomised retrospective analysis of 95 consecutive patients with advanced NSCLC who received radiation therapy treatment either during or within 60 days of nivolumab showed a median overall survival (OS) of 22.4 months vs 8.6 months 45 . The definition of radiation therapy within 60 days after immunotherapy as concurrent was used because of the long half‐life of nivolumab, a feature common to immune checkpoint inhibitors.…”

Global research landscape and trends of cancer radiotherapy plus immunotherapy: A bibliometric analysis

“…Contrary to the findings of the PACIFIC trial, subgroup analyses revealed that patients with PD-L1-negative tumors derived the most significant benefit from incorporating RT. A retrospective study involving 95 individuals diagnosed with advanced NSCLC demonstrated that those who received nivolumab in combination with RT (including SABR, mHFRT, or CFRT) experienced a mPFS of 6.3 months and a mOS of 11.9 months [ 38 ].…”

Safety and efficacy of radiotherapy/chemoradiotherapy combined with immune checkpoint inhibitors for non-small cell lung cancer: A systematic review and meta-analysis

“…Bassanelli et al. ( 96 ) suggested that the first ≤60 days prior to the completion of RT (mOS, 22.4 months vs. 8.6 months, p = 0.005) was the most appropriate window for ICI administration. However, Bryant et al.…”