TY - JOUR
T1 - Progression risk among responders to PD-1/PD-L1 blockade is primarily stratified by response depth
T2 - A nationwide cohort study of 2127 patients with melanoma, RCC, and NSCLC
AU - Andersen, Rikke
AU - Jespersen, Mette Syberg
AU - Presti, Mario
AU - Bjornhart, Birgitte
AU - Østby, Anne-Cathrine
AU - Darras, Anne Kirstine Moeller
AU - Garitaonaindia, Yago
AU - Ruhlmann, Christina Halgaard
AU - Frank, Malene Støchkel
AU - Schmidt, Henrik
AU - Friis, Rasmus Blechingberg
AU - Guldbrandt, Louise Mahncke
AU - Henriksen, Jon Røikjær
AU - Bjerrum, Andreas
AU - Simonsen, Kira Schreiner
AU - Palshof, Jesper Andreas
AU - Borch, Troels Holz
AU - Andersen, Jon Lykkegaard
AU - Kjaer, Soeren
AU - Jensen, Niels Viggo
AU - Azimi, Aziza
AU - Iversen, Ane Bundsbaek
AU - Meldgaard, Peter
AU - Steen, Sara Grønbech
AU - Khan, Shawez
AU - Luczak, Adam Andrzej
AU - Wahlstrøm, Stine
AU - Zitnjak, Daniela
AU - Svane, Inge Marie
AU - Fristrup, Niels
AU - Kristiansen, Charlotte
AU - Persson, Gitte Fredberg
AU - Bastholt, Lars
AU - Poehl, Mette
AU - Ellebaek, Eva
AU - Donia, Marco
N1 - Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.
PY - 2026/6/5
Y1 - 2026/6/5
N2 - PURPOSE: Among responders to PD-1/PD-L1 blockade, it remains unclear whether tumour type and traditional baseline patient and tumour characteristics provide additional prognostic information for progression risk beyond response depth.METHODS: In this nationwide, population-based cohort study, we identified adults with metastatic melanoma (MM), renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 monotherapy or dual checkpoint blockade. Analyses were restricted to responders by investigator-assessed RECIST (complete or partial response) with outcomes administratively censored at 5 years. Prespecified baseline and on-treatment variables were evaluated for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox models and assessed for consistency across tumour types.RESULTS: Among 2127 responders, PFS trajectories within response depth categories (complete response and partial response) were highly similar across MM, RCC, and NSCLC. Prespecified variables with prognostic value in the overall population, including performance status and treatment line, provided limited additional prognostic information once response depth was known. Depth of response (complete vs partial) was the strongest independent factor associated with progression risk within each tumour cohort.CONCLUSIONS: Among patients with MM, RCC, or NSCLC who achieved an objective response to PD-1/PD-L1 blockade, tumour type and traditional baseline prognostic factors provided limited additional stratification of progression risk once response depth was known. These findings suggest that, within the tumour types studied, response durability is primarily associated with response depth rather than other known clinical features, supporting prospective evaluation of response-guided follow-up strategies and interventions designed to deepen responses.
AB - PURPOSE: Among responders to PD-1/PD-L1 blockade, it remains unclear whether tumour type and traditional baseline patient and tumour characteristics provide additional prognostic information for progression risk beyond response depth.METHODS: In this nationwide, population-based cohort study, we identified adults with metastatic melanoma (MM), renal cell carcinoma (RCC), or non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 monotherapy or dual checkpoint blockade. Analyses were restricted to responders by investigator-assessed RECIST (complete or partial response) with outcomes administratively censored at 5 years. Prespecified baseline and on-treatment variables were evaluated for associations with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox models and assessed for consistency across tumour types.RESULTS: Among 2127 responders, PFS trajectories within response depth categories (complete response and partial response) were highly similar across MM, RCC, and NSCLC. Prespecified variables with prognostic value in the overall population, including performance status and treatment line, provided limited additional prognostic information once response depth was known. Depth of response (complete vs partial) was the strongest independent factor associated with progression risk within each tumour cohort.CONCLUSIONS: Among patients with MM, RCC, or NSCLC who achieved an objective response to PD-1/PD-L1 blockade, tumour type and traditional baseline prognostic factors provided limited additional stratification of progression risk once response depth was known. These findings suggest that, within the tumour types studied, response durability is primarily associated with response depth rather than other known clinical features, supporting prospective evaluation of response-guided follow-up strategies and interventions designed to deepen responses.
KW - Cohort study
KW - Complete response
KW - Immune checkpoint inhibitors
KW - PD-1/PD-L1 blockade
KW - Partial response
KW - Progression-free survival
KW - Kidney Neoplasms/drug therapy
KW - Immune Checkpoint Inhibitors/therapeutic use
KW - Humans
KW - Middle Aged
KW - Male
KW - Disease Progression
KW - Lung Neoplasms/drug therapy
KW - Progression-Free Survival
KW - B7-H1 Antigen/antagonists & inhibitors
KW - Carcinoma, Non-Small-Cell Lung/drug therapy
KW - Melanoma/drug therapy
KW - Aged, 80 and over
KW - Female
KW - Carcinoma, Renal Cell/drug therapy
KW - Adult
KW - Aged
KW - Programmed Cell Death 1 Receptor/antagonists & inhibitors
KW - Cohort Studies
U2 - 10.1016/j.ejca.2026.116872
DO - 10.1016/j.ejca.2026.116872
M3 - Article
C2 - 42284973
SN - 0959-8049
VL - 243
JO - European Journal of Cancer
JF - European Journal of Cancer
M1 - 116872
ER -