INVESTIGATING THE CORRELATION BETWEEN PROGRESSION-FREE SURVIVAL (PFS) AND OVERALL SURVIVAL (OS) IN FIRST-LINE (1L) CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC LYMPHOMA (CLL/SLL)
Author(s)
Enrico De Nigris, MSc1, Dylan Maciel, MSc2, Oluwaseun Egunsola, PhD3, Ali Mojebi, MD4, Kiran Gupta, M.Pharm, PhD5.
1MSD (UK) Ltd, London, United Kingdom, 2Precision AQ, VANCOUVER, BC, Canada, 3Precision AQ, Bethesda, MD, USA, 4Precision AQ, Vancouver, BC, Canada, 5Merck & Co., Inc., Rahway, NJ, USA.
1MSD (UK) Ltd, London, United Kingdom, 2Precision AQ, VANCOUVER, BC, Canada, 3Precision AQ, Bethesda, MD, USA, 4Precision AQ, Vancouver, BC, Canada, 5Merck & Co., Inc., Rahway, NJ, USA.
OBJECTIVES: Given the long maturation time of OS in indolent oncology diseases, PFS is often used as a surrogate for OS in regulatory and health technology assessment (HTA) settings. Considering limited evidence on the association between these two endpoints in 1L CLL/SLL, this analysis aimed to evaluate the correlation between PFS and OS in this population.
METHODS: A SLR of Embase®, MEDLINE®, CENTRAL and conference proceedings (search date: June 15, 2025) identified clinical trials in 1L CLL/SLL reporting OS and PFS. Arm-level correlations were estimated between PFS rates (at 12, 18, and 24 months) and OS rates (at 24, 36, and 48 months) in trials reporting Kaplan-Meier data, using weighted Spearman correlation coefficient (ρ).
RESULTS: Of the 41 trials included in the SLR, 27 were included in the analyses based on availability of hazard ratios (trial-level only) or Kaplan-Meier data, with 11,526 patients overall. Median follow-up ranged from 22.5 and 96 months. In the arm-level analyses, ρ was 0.83 (0.70-0.90), 0.85 (0.74-0.91), and 0.82 (0.67-0.90) for correlations between 12-month PFS and 24, 36, and 48-month OS, respectively. For 18-month PFS, ρ was 0.83 (0.70-0.90), 0.86 (0.76-0.91), and 0.85 (0.70-0.92), respectively; and for 24-month PFS, it was 0.82 (0.70-0.88) with 36-month OS and 0.80 (0.65-0.88) with 48-month OS.
CONCLUSIONS: This analysis showed consistently moderate-to-strong correlations between PFS and OS in the arm-level analyses, suggesting that PFS could be an adequate surrogate endpoint for OS. Further trial based level assessments, including surrogate threshold effect (STE) analysis to determine the minimum change in PFS required to predict an OS benefit—are required to fully validate PFS as a surrogate endpoint in 1L CLL/SLL.
METHODS: A SLR of Embase®, MEDLINE®, CENTRAL and conference proceedings (search date: June 15, 2025) identified clinical trials in 1L CLL/SLL reporting OS and PFS. Arm-level correlations were estimated between PFS rates (at 12, 18, and 24 months) and OS rates (at 24, 36, and 48 months) in trials reporting Kaplan-Meier data, using weighted Spearman correlation coefficient (ρ).
RESULTS: Of the 41 trials included in the SLR, 27 were included in the analyses based on availability of hazard ratios (trial-level only) or Kaplan-Meier data, with 11,526 patients overall. Median follow-up ranged from 22.5 and 96 months. In the arm-level analyses, ρ was 0.83 (0.70-0.90), 0.85 (0.74-0.91), and 0.82 (0.67-0.90) for correlations between 12-month PFS and 24, 36, and 48-month OS, respectively. For 18-month PFS, ρ was 0.83 (0.70-0.90), 0.86 (0.76-0.91), and 0.85 (0.70-0.92), respectively; and for 24-month PFS, it was 0.82 (0.70-0.88) with 36-month OS and 0.80 (0.65-0.88) with 48-month OS.
CONCLUSIONS: This analysis showed consistently moderate-to-strong correlations between PFS and OS in the arm-level analyses, suggesting that PFS could be an adequate surrogate endpoint for OS. Further trial based level assessments, including surrogate threshold effect (STE) analysis to determine the minimum change in PFS required to predict an OS benefit—are required to fully validate PFS as a surrogate endpoint in 1L CLL/SLL.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
SA50
Topic
Clinical Outcomes, Methodological & Statistical Research, Study Approaches
Topic Subcategory
Literature Review & Synthesis
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, Oncology