Efficacy and predictors of rechallenge with immune checkpoint inhibitors in non‐small cell lung cancer

Abstract

Background: The efficacy of rechallenge with immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) patients has not yet been fully clarified. This study aimed to identify the clinical characteristics of patients with NSCLC who benefited from rechallenge with ICIs. Methods: We retrospectively reviewed the clinical records of 24 patients who were diagnosed with NSCLC and rechallenged with ICIs between August 2016 and July 2021.Results: Of the 24 patients included in the study, 11 were in the responder group (45.8%) and 13 in the nonresponder group (54.2%). The number of patients who used a different ICI from that used in the initial therapy was significantly higher in the responder group than in the nonresponder group (p = 0.006). Multivariate analysis identified lung metastasis and female sex as significant independent risk factors for nonresponse to rechallenge with ICIs. Compared to the nonresponder group, the duration of treatment after rechallenge with ICIs was significantly longer in the responder group (p = 0.016), and there was a trend toward longer overall survival (p = 0.059). Conclusions: Patients with lung cancer who were rechallenged with ICIs and without progressive disease after initial ICI therapy were able to continue ICI therapy for a longer period of time. This may be associated with longer survival. Patients with lung metastases and female patients are more likely to be nonresponsive to rechallenge with ICIs. Administration of a different type of ICI from that used in the initial ICI therapy may result in disease control. K E Y W O R D S immune checkpoint inhibitors, lung neoplasm, non-small-cell lung carcinoma

Heterogeneous Outcomes of Immune Checkpoint Inhibitor Rechallenge in Patients With NSCLC: A Systematic Review and Meta-Analysis

“…The following information was extracted: first author, year of publication, country, study design, treatment period, number, sex and mean age of patients at initial treatment, regimens and therapy line of initial ICI and ICI rechallenge, tumor proportion status, best response to ICI treatment, number of patients who experienced grade 3 or 4 irAE after initial treatment and after rechallenge, median progression-free survival (PFS) (in mo), the cessation reasons of initial ICI, and interval time between initial ICI and ICI rechallenge (Table 1). [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Study quality assessments were performed according to the Newcastle-Ottawa Scale, which evaluated the study design based on eight questions regarding population selection, comparability, and exposure. 12…”

“…The main clinical characteristics and outcomes, including grade 3/4 irAE, the best response to ICI, and PFS, are found in Table 1. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Among them, the discontinuation of initial ICI occurred in 131 patients owing to different grades of irAE, 251 patients owing to disease progression during ICI treatment, and 42 patients owing to clinical decision such as after a defined…”

Pembrolizumab for first-line treatment of advanced unresectable or metastatic esophageal or gastroesophageal junction cancer

“…The efficacy of ICI rechallenge has been reported for patients with non-small-cell lung cancer. 52 However, if patients received preoperative docetaxel + CF and postoperative nivolumab and showed early recurrence, the efficacy was limited. Therefore, new agents are needed.…”

Disease progression status during initial immune checkpoint inhibitor (ICI) affects the clinical outcome of ICI retreatment in advanced non‐small cell lung cancer patients

“…The reported clinical outcomes of ICI retreatment in advanced NSCLC patients are varied: ORR ranged from 0 to 43% and PFS from 1.5 to 15.4 months. [2][3][4][5][6][7][8][9][10][11][12] However, a meta-analysis reported an ORR of 12.4% and a median PFS of 3.7 months after ICI retreatment. 19 Our study F I G U R E 3 (A) Progression-free survival (PFS) for ICI retreatment according to initial ICI response in PD group and (B) Without PD group.…”

“…The reported clinical outcomes of ICI retreatment in advanced NSCLC patients are varied: ORR ranged from 0 to 43% and PFS from 1.5 to 15.4 months 2–12 . However, a meta‐analysis reported an ORR of 12.4% and a median PFS of 3.7 months after ICI retreatment 19 .…”