58: Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

Friday, March 24, 2023

10:34 AM – 10:44 AM

Location: Veterans Memorial Auditorium

Abstract Presenter(s)

Kristen E. Rhodin, MD

General Surgery Resident
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

First Author(s)

Kristen E. Rhodin, MD

General Surgery Resident
Duke University Medical Center
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

Author(s)

SJ

Sin-Ho Jung, PhD

Professor of Biostatistics and Bioinformatics
Duke University, United States

Disclosure information not submitted.
Kelly Elleson, MS, MD

Breast Surgical Oncology Fellow
Moffitt Cancer Center
Tampa, Florida, United States

Disclosure information not submitted.
DD

Danielle DePalo, MD

Research Fellow
Moffitt Cancer Center, United States

Disclosure information not submitted.
RS

Richard Straker, MD

General Surgery Resident
Hospital of the University of Pennsylvania, United States

Disclosure information not submitted.
SM

Sophia McKinley, MD

Complex General Surgical Oncology Fellow
Memorial Sloan Kettering Cancer Center, United States

Disclosure information not submitted.
Kate Beekman

Medical Student
University of South Florida, Florida, United States

Disclosure information not submitted.
Lily Parker (she/her/hers)

Medical Student
University of South Florida, United States

Disclosure information not submitted.
SC

Suephy Chen, MD, MS

Professor of Dermatology
Duke University Medical Center, United States

Disclosure information not submitted.
AS

April Salama, MD

Associate Professor of Medicine
Duke University Medical Center, United States

Disclosure information not submitted.
MI

Matthew K. Iyer, MD, PhD

Complex General Surgical Oncology Fellow
Duke University Medical Center, United States

Disclosure information not submitted.
Edmund Bartlett, MD

Assistant Attending, Gastric and Mixed Tumor Service
Memorial Sloan Kettering Cancer Center
New York, New York, United States

Disclosure(s): Excite International Inc: Other (Terminated, January 3, 2022); SkylineDx: Research Grant (Ongoing)
Giorgos Karakousis, MD

Professor of Surgery
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States

Disclosure information not submitted.
Jonathan S. Zager, MD

Chief Academic Officer, Director of Regional Therapies, Senior member and Professor of Surgery
H. Lee Moffitt Cancer Center
Tampa, Florida, United States

Disclosure(s): Castle Biosciences: Advisor (Ongoing), Consultant (Ongoing); Delcath Systems: Advisor (Ongoing), Research Grant (Ongoing); High Flow ILI: Patent Beneficiary (Ongoing); Merck & Co., Inc.: Advisor (Ongoing), Consultant (Ongoing); Philogen: Advisor (Ongoing), Consultant (Ongoing), Research Grant (Ongoing); Provectus Inc: Research Grant (Ongoing); Replimmune: Advisor (Ongoing), Consultant (Ongoing)
Doug Tyler, MD, MSHCT

Professor and Chairman, Department of Surgery
University of Texas Medical Branch

Disclosure(s): No financial relationships to disclose
Georgia Beasley, MD, MHSc (she/her/hers)

Associate Professor of Surgery, Associate Professor of Medicine, Co-director Duke Melanoma Program
Duke University
Durham, North Carolina, United States

Disclosure(s): No financial relationships to disclose

Disclosure(s):

Kristen E. Rhodin, MD: No financial relationships to disclose

Edmund Bartlett, MD: Excite International Inc: Other (Terminated, January 3, 2022); SkylineDx: Research Grant (Ongoing)

Jonathan S. Zager, MD: Castle Biosciences: Advisor (Ongoing), Consultant (Ongoing); Delcath Systems: Advisor (Ongoing), Research Grant (Ongoing); High Flow ILI: Patent Beneficiary (Ongoing); Merck & Co., Inc.: Advisor (Ongoing), Consultant (Ongoing); Philogen: Advisor (Ongoing), Consultant (Ongoing), Research Grant (Ongoing); Provectus Inc: Research Grant (Ongoing); Replimmune: Advisor (Ongoing), Consultant (Ongoing)

Doug Tyler, MD, MSHCT: No financial relationships to disclose

Georgia Beasley, MD, MHSc: No financial relationships to disclose

Introduction: Immune checkpoint inhibitors (ICI) have been shown to reduce recurrence in patients with stage III cutaneous melanoma; however, the optimal time to initiate adjuvant ICI following oncologic 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, pathologic stage III cutaneous melanoma receiving adjuvant ICI were identified within a multi-institutional retrospective cohort (2014-2022). Patients were stratified by time to induction of adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. The primary outcome was recurrence free survival (RFS) which was compared among time strata with Kaplan Meier and Cox proportional hazards methods. Conditional landmark analysis was performed to limit immortal time bias.

Results: Altogether, 626 patients were identified with a median time to adjuvant ICI of 7.1 weeks (IQR 4.8-10.6). 39% (n=246) patients initiated adjuvant ICI within 6 weeks, 42.2% (n=264) within 6-12 weeks, and 18.8% (n=118) greater than 12 weeks from surgery. The type of adjuvant ICI, in decreasing order of prevalence, included: nivolumab (68.1%), pembrolizumab (18.5%), ipilimumab (11%), or a combination (2.1%). In a multivariable Cox regression model, adjusting for histology, nodal tumor burden (mm), and pathologic stage, we found that increased time to adjuvant ICI (per week) was associated with improved RFS (HR 0.96, 95% CI 0.93-0.99; p=0.02). Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS (40.4 vs. 55.9 vs. 60.8% 36-month RFS, respectively) (Figure). This survival disadvantage was preserved in a conditional landmark analysis.

Conclusions: Patients with stage III cutaneous melanoma may benefit from waiting at least 6 weeks after oncologic resection before initiating adjuvant ICI. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Learning Objectives:

Upon completion, participant will be able to describe indications for adjuvant therapy in melanoma
Upon completion, participant will be able to describe implications of adjuvant therapy on outcomes in melanoma
Upon completion, participant will be able to describe implications of timing of adjuvant therapy in melanoma