Validation of Real-World Recurrence-Free Survival (rwRFS) and Distant Metastasis-Free Survival(rwDMFS) Endpoints in Early-Stage Melanoma
Author(s)
Carole R. Berini, PhD1, Jessica K. Paulus, ScD1, Malcolm Charles, M.S.1, Zhaohui Su, PhD1, Paul Conkling, M.D.1, Nina Balanchivadze, MD, FACP2, Shan Jiang, PhD3, Kaushal Desai, PhD3.
1Ontada, Boston, MA, USA, 2The US Oncology Network, Norfolk, VA, USA, 3Merck, Rahway, NJ, USA.
1Ontada, Boston, MA, USA, 2The US Oncology Network, Norfolk, VA, USA, 3Merck, Rahway, NJ, USA.
Presentation Documents
OBJECTIVES: Real-world (RW) evidence has been used to evaluate the real-world effectiveness of various advanced stage cancer treatments. Compared to measures such as progression-free survival and overall survival, less is known regarding the validity of real-world early-stage clinical outcomes in early-stage melanoma. We therefore applied trial emulation methods to examine the concordance between rREFS and rwDMFS estimates from the KEYNOTE-716 trial as a measure of real-world endpoint validity.
METHODS: This retrospective observational study used electronic health records from The US Oncology Network to identify patients diagnosed with stage IIB-IIC cutaneous melanoma between 01/01/2018 and 05/31/2023 who had not initiated adjuvant therapy 12 weeks post resection with clear margins. Patients were followed through 07/31/2023. Trial eligibility criteria were applied to define a RW-cohort closely matching KEYNOTE-716. Matching-Adjusted Indirect Comparison analysis was performed to adjust for available demographic and clinical characteristics (age, race, ethnicity, clinical stage at diagnosis, and ECOG). Hazard ratios (HR) were used to compare rwRFS and rwDMFS with estimates from the placebo arm of KEYNOTE-716.
RESULTS: Patients in the RW cohort (n=248) were older (71 vs. 61 median years) and more had ECOG Stage performance status 1 (37% vs 7%). There were not statistically significant differences between the KEYNOTE-716 placebo arm RFS and rwRFS in unadjusted (HR: 1.03, 95% CI: 0.67 - 1.59) nor adjusted (HR: 0.85, 95% CI: 0.52, 1.40) analyses. Similarly, there were no statistically significant differences in KEYNOTE-716 placebo arm DMFS and rwDMFS in either unadjusted (HR: 1.36, 95% CI: 0.84 - 2.19) nor adjusted (HR: 1.20, 95% CI: 0.76, 1.97) analyses.
CONCLUSIONS: With the application of real-world definitions to align key study design elements with the trial, and leveraging curated data, endpoints rwRFS and rwDMFS are concordant with clinical trial estimates in early-stage melanoma. These results increase confidence in the validity of real-world outcomes for investigating early-stage melanoma.
METHODS: This retrospective observational study used electronic health records from The US Oncology Network to identify patients diagnosed with stage IIB-IIC cutaneous melanoma between 01/01/2018 and 05/31/2023 who had not initiated adjuvant therapy 12 weeks post resection with clear margins. Patients were followed through 07/31/2023. Trial eligibility criteria were applied to define a RW-cohort closely matching KEYNOTE-716. Matching-Adjusted Indirect Comparison analysis was performed to adjust for available demographic and clinical characteristics (age, race, ethnicity, clinical stage at diagnosis, and ECOG). Hazard ratios (HR) were used to compare rwRFS and rwDMFS with estimates from the placebo arm of KEYNOTE-716.
RESULTS: Patients in the RW cohort (n=248) were older (71 vs. 61 median years) and more had ECOG Stage performance status 1 (37% vs 7%). There were not statistically significant differences between the KEYNOTE-716 placebo arm RFS and rwRFS in unadjusted (HR: 1.03, 95% CI: 0.67 - 1.59) nor adjusted (HR: 0.85, 95% CI: 0.52, 1.40) analyses. Similarly, there were no statistically significant differences in KEYNOTE-716 placebo arm DMFS and rwDMFS in either unadjusted (HR: 1.36, 95% CI: 0.84 - 2.19) nor adjusted (HR: 1.20, 95% CI: 0.76, 1.97) analyses.
CONCLUSIONS: With the application of real-world definitions to align key study design elements with the trial, and leveraging curated data, endpoints rwRFS and rwDMFS are concordant with clinical trial estimates in early-stage melanoma. These results increase confidence in the validity of real-world outcomes for investigating early-stage melanoma.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
RWD156
Topic
Real World Data & Information Systems
Topic Subcategory
Reproducibility & Replicability
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology