Safety and Efficacy of Re-treating with Immunotherapy after Immune-Related Adverse Events in Patients with NSCLC

作者：Fernando C. Santini, Hira Rizvi, Andrew J. Plodkowski, Ai Ni, Mario E. Lacouture, Maya Gambarin‐Gelwan, Olivia Wilkins, Elizabeth Panora, Darragh Halpenny, Niamh M. Long, Mark G. Kris, Charles M. Rudin, Jamie E. Chaft, Matthew D. Hellmann · 发表于：Cancer Immunology Research · 年份：2018 · DOI：10.1158/2326-6066.cir-17-0755 · 被引用次数：332 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、Lung Cancer Treatments and Mutations

Abstract Considering retreatment following recovery from an immune-related adverse event (irAE) is a common clinical scenario, but the safety and benefit of retreatment is unknown. We identified patients with advanced non–small cell lung cancer (NSCLC) treated with anti-PD-(L)1 who had treatment held due to irAEs and divided them into two groups: those retreated with anti-PD-(L)1 (retreatment cohort) or those who had treatment stopped (discontinuation cohort). Out of 482 NSCLC patients treated with anti-PD-(L)1, 68 (14%) developed a serious irAE requiring treatment interruption. Of these, 38 (56%) were retreated and 30 (44%) had treatment discontinued. In the retreatment cohort, 18 (48%) patients had no subsequent irAEs, 10 (26%) had recurrence of the initial irAE, and 10 (26%) had a new irAE. Most recurrent/new irAEs were mild (58% grade 1–2) and manageable (84% resolved or improved to grade 1). Two treatment-related deaths occurred. Recurrent/new irAEs were more likely if the initial irAE required hospitalization, but the initial grade and time to retreatment did not influence risk. Among those with no observed partial responses prior to the irAE, progression-free survival (PFS) and overall survival (OS) were longer in the retreatment cohort. Conversely, for those with objective responses prior to the irAE, PFS and OS were similar in the retreatment and discontinuation cohorts. Among patients with early objective responses prior to a serious irAE, outcomes were similar, whe...