Association between the occurrence of immune-related adverse events and survival outcomes in patients with cancer treated with perioperative immune checkpoint inhibitors: A systematic review and meta-analysis.

Authors

null

Taiga KOMATSU

St. Luke's International Hospital, Chuo-Ku, Japan

Taiga KOMATSU , Kohei Chida , Nobuyuki Horita , Alessio Cortellini , Abdul Rafeh Naqash , Yu Fujiwara

Organizations

St. Luke's International Hospital, Chuo-Ku, Japan, Roswell Park Comprehensive Cancer Center, Buffalo, NY, Chemotherapy Center, Yokohama City University Hospital, Yokohama, Japan, Division of Surgery and Cancer, Imperial College, London, United Kingdom, Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center, University of Oklahoma, Oklahoma City, OK

Research Funding

No funding sources reported

Background: Although multiple studies have revealed that the occurrence of immune-related adverse events (irAEs) is associated with better survival in patients with advanced cancer, the association in patients with early-stage disease in the perioperative setting remains unclear. We performed a systematic review and meta-analysis to evaluate this association in the neoadjuvant and adjuvant settings. Methods: We performed a database search in PubMed/MEDLINE and Embase to identify eligible articles up to March 2024. We included studies evaluating the association between the occurrence of irAEs and survival outcomes in patients with solid tumors receiving at least one ICI in the perioperative setting. Cancer type, ICI agent, the number of patients, and survival outcomes (hazard ratio [HR] with 95% confidence interval [CI]) were summarized. We performed a random-effect model meta-analysis of survival outcomes that contained HR and 95% CI information from more than two studies. Results: After screening 884 articles, we found 15 eligible articles of which four studies reporting only treatment-related adverse events without irAE information were excluded. Finally, 11 studies (Clinical trials: n=3, Cohort studies: n=8) analyzing the association between the incidence of irAEs and survival were identified. Melanoma, triple-negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), and urothelial carcinoma were evaluated in seven, two, one, and one study, respectively. While ten studies defined the irAE group as any-type and any-grade irAEs, one study defined the irAE group as any-type and grade 2-5 irAEs. OS was evaluated in five studies (four studies for melanoma), of which two studies suggested that the occurrence of irAEs was associated with longer OS. A meta-analysis of three studies showed a tendency of the association between the occurrence of any-type and any-grade irAEs and longer OS (Pooled HR=0.69, 95% CI 0.47-1.00, p = 0.05). RFS was evaluated in eight studies (seven for melanoma), of which seven studies indicated the association between the incidence of any-type irAEs (any-grade: 6 studies, grade 2-5: 1 study) and longer RFS. A meta-analysis of five studies revealed a significant association between the occurrence of any-type irAEs (any-grade: 4 studies, grade 2-5: 1 study) and longer RFS (Pooled HR=0.52, 95% CI 0.41 - 0.67, p < 0.0001]); however, Funnel plot indicated a presence of publication bias. Conclusions: This study suggests an association between irAEs and longer survival from perioperative ICI therapy, particularly in patients with melanoma. The result should be cautiously interpreted given a possible presence of publication and immortal bias. Further prospective studies and individual patient data meta-analysis are needed to validate this result.

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Abstract Details

Meeting

2024 ASCO Breakthrough

Session Type

Poster Session

Session Title

Poster Session A

Track

Gastrointestinal Cancer,Central Nervous System Tumors,Developmental Therapeutics,Genitourinary Cancer,Quality of Care,Healthcare Equity and Access to Care,Population Health,Viral-Mediated Malignancies

Sub Track

Immunotherapies

Citation

J Clin Oncol 42, 2024 (suppl 23; abstr 39)

DOI

10.1200/JCO.2024.42.23_suppl.39

Abstract #

39

Poster Bd #

B2

Abstract Disclosures