Timing of adjuvant immunotherapy in stage III melanoma, does it matter? Journal Article


Authors: Rhodin, K. E.; Jung, S. H.; Elleson, K.; DePalo, D.; Straker, R.; McKinley, S.; Beekman, K.; Parker, L.; Chen, S.; Iyer, M. K.; Salama, A. K. S.; Bartlett, E.; Karakousis, G.; Zager, J. S.; Tyler, D. S.; Beasley, G. M.
Article Title: Timing of adjuvant immunotherapy in stage III melanoma, does it matter?
Abstract: Background: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. Methods: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6–12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. Results: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6–12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. Conclusions: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes. © 2023, Society of Surgical Oncology.
Keywords: adult; cancer survival; controlled study; human tissue; aged; retrospective studies; major clinical study; overall survival; histopathology; cancer recurrence; monotherapy; cancer adjuvant therapy; cancer patient; cancer staging; lymph node dissection; sentinel lymph node biopsy; ipilimumab; cancer immunotherapy; melanoma; skin neoplasms; tumor volume; cohort analysis; pathology; retrospective study; skin tumor; immunotherapy; cancer registry; adjuvant radiotherapy; cutaneous melanoma; recurrence free survival; wide excision; procedures; immune checkpoint inhibitor; combination drug therapy; nivolumab; time to treatment; humans; human; male; female; article; pembrolizumab; melanoma, cutaneous malignant
Journal Title: Annals of Surgical Oncology
Volume: 30
Issue: 11
ISSN: 1068-9265
Publisher: Springer  
Date Published: 2023-10-01
Start Page: 6340
End Page: 6352
Language: English
DOI: 10.1245/s10434-023-13935-0
PUBMED: 37574517
PROVIDER: scopus
PMCID: PMC10530114
DOI/URL:
Notes: Article -- Source: Scopus
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