Factors associated with disease progression after discontinuation of immune checkpoint inhibitors for immune-related toxicity in patients with advanced non-small cell lung cancer Journal Article
| Authors: | Pecci, F.; Thummalapalli, R.; Alden, S. L.; Ricciuti, B.; Alessi, J. V.; Elkrief, A.; Rizvi, H.; Wang, X.; Jeng, M.; Egger, J. V.; Vaz, V. R.; Barrichello, A.; Lamberti, G.; Di Federico, A.; Santo, V.; Rossato de Almeida, G.; Gandhi, M.; Clark, P.; Nishino, M.; Johnson, B. E.; Hellmann, M.; Schoenfeld, A. J.; Awad, M. M. |
| Article Title: | Factors associated with disease progression after discontinuation of immune checkpoint inhibitors for immune-related toxicity in patients with advanced non-small cell lung cancer |
| Abstract: | PURPOSE: Among patients with advanced non-small cell lung cancer (NSCLC) who discontinue immune checkpoint inhibitors (ICI) because of immune-related adverse events (irAE), post-discontinuation clinical outcomes and factors associated with disease progression after discontinuation are largely unknown. EXPERIMENTAL DESIGN: Clinicopathologic data were abstracted from patients with advanced NSCLC who received ICI and discontinued treatment because of irAE. Factors associated with post-discontinuation progression-free survival (PFS) and post-discontinuation overall survival (OS) were evaluated. RESULTS: Of 2,794 patients, 10% (N = 271) discontinued ICI because of irAE, and the median duration of ICI treatment before discontinuation for irAE was 5.9 months (range, 0.03-73.5). A longer treatment duration before discontinuation for irAE was associated with improved post-discontinuation outcomes: for patients on ICI for <3 months (N = 89), 3 to 6 months (N = 49), and >6 months (N = 133) before discontinuing for irAE, the median post-discontinuation PFS was 6.2, 13.9, and 25.8 months (P < 0.001), respectively, and the median post-discontinuation OS was 21.7, 42.7, and 86.9 months (P < 0.001), respectively. At multivariable analyses, predictors of longer post-discontinuation PFS were PD-L1 ≥ 50%, complete response/partial response (CR/PR) to treatment, and treatment duration before discontinuation between 3 to 6 months and >6 months; predictors of longer post-discontinuation OS were nonsquamous histology, CR/PR, and treatment duration before discontinuation >6 months. The use of immunosuppressive agents for toxicity management did not affect post-discontinuation outcomes. CONCLUSIONS: A longer treatment duration before discontinuation, a best objective response of CR/PR, PD-L1 ≥50%, and nonsquamous histology may help clinicians identify patients who may experience long-term disease control after discontinuation of ICI for irAE. ©2025 American Association for Cancer Research. |
| Keywords: | adult; aged; aged, 80 and over; middle aged; retrospective studies; mortality; carcinoma, non-small-cell lung; lung neoplasms; pathology; retrospective study; lung tumor; immunology; disease progression; drug therapy; disease exacerbation; adverse drug reaction; treatment withdrawal; non small cell lung cancer; etiology; withholding treatment; immune checkpoint inhibitor; very elderly; humans; human; male; female; drug-related side effects and adverse reactions; immune checkpoint inhibitors |
| Journal Title: | Clinical Cancer Research |
| Volume: | 31 |
| Issue: | 12 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2025-06-15 |
| Start Page: | 2413 |
| End Page: | 2425 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-24-2990 |
| PUBMED: | 40247431 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
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