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. 2025 Feb 1;11(2):154-161.
doi: 10.1001/jamaoncol.2024.5672.

Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy

Jonas Saal  1   2   3 , Markus Eckstein  4   5   6 , Manuel Ritter  3   7 , Peter Brossart  1   3 , Julian Luetkens  8   9 , Jörg Ellinger  3   7 , Viktor Grünwald  10 , Michael Hölzel  2   3 , Niklas Klümper  2   3   7
Affiliations

Dissection of Progressive Disease Patterns for a Modified Classification for Immunotherapy

Jonas Saal et al. JAMA Oncol. .

Erratum in

  • Errors in Figure 1.
    [No authors listed] [No authors listed] JAMA Oncol. 2025 Feb 1;11(2):189. doi: 10.1001/jamaoncol.2025.0057. JAMA Oncol. 2025. PMID: 39976630 Free PMC article. No abstract available.

Abstract

Importance: Progressive disease (PD) in patients treated with immune checkpoint inhibitors (ICIs) varies widely in outcomes according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Efforts to modify RECIST for ICI treatment have not resolved the heterogeneity in PD patterns, posing a clinical challenge.

Objective: To develop and validate a modified PD classification based on PD patterns and evaluate its association with postprogression survival (PPOS) in patients treated with the programmed cell death protein ligand 1 antibody atezolizumab across various solid tumors.

Design, setting, and participants: This study analyzed data from 5 phase 3 trials (IMmotion151, IMvigor211, OAK, Impower133, and IMspire150) involving patients treated with atezolizumab for renal cell carcinoma (RCC), urothelial carcinoma, small cell lung cancer, non-small cell lung cancer, and melanoma. This post hoc analysis was conducted from March to September 2024.

Exposure: Treatment with atezolizumab.

Main outcomes and measures: The primary outcome was the association of PD patterns with PPOS. Seven PD patterns were identified based on the enlargement of target and nontarget lesions or new lesions and their combinations.

Results: A total of 1377 patients were analyzed across the 5 trials. In RCC, 7 PD patterns significantly affected prognosis. The 6-month PPOS probability ranged from 26% for progression in target and nontarget lesions plus new lesions to 90% for progression in either target or nontarget lesions alone. A modified PD classification was developed that categorized PD into 3 risk levels: low risk (progression of existing lesions), intermediate risk (new lesions without progression of existing lesions), and high risk (progression of existing lesions plus new lesions). This score was associated with PPOS in ICI-treated RCC, with hazard ratios of 0.23 (95% CI, 0.13-0.41; P < .001) and 0.39 (95% CI, 0.23-0.66; P < .001) for low-risk and intermediate-risk PD compared with high-risk PD, respectively. Validation in additional trials confirmed the score's applicability across various tumors.

Conclusions and relevance: In this study, a survival score was developed based on PD patterns. The risk classification was associated with PPOS across various solid tumors treated with immunotherapy and may therefore enhance prognostication and clinical decision-making, potentially providing a valuable tool for treating patients with PD who are receiving immunotherapy.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Luetkens reported personal fees from Novartis, Philips Healthcare, Siemens Healthineers, Bayer Healthcare, and GE Healthcare outside the submitted work. Dr Grünwald reported personal fees from AAA/Novartis, Amgen, Apogepha, Astellas, AstraZeneca, Bristol Myers Squibb, EISAI, Ipsen, Janssen-Cilag, Merck Serono, MSD Oncology, Ono Pharmaceutical, Pfizer, Cureteq, Debiopharm, Gilead Sciences, Oncorena, PCI Biotech, and Synthekine outside the submitted work. Dr Hölzel reported personal fees from BioTex Inc/OncoMagnetix and TME Pharma, grants from TME Pharma, and travel support from TME Pharma outside the submitted work. Dr Klümper reported personal fees from AstraZeneca, Merck, Astellas, Novartis, Eisai, MSD, and Bicycle Therapeutics outside the submitted work. No other disclosures were reported.

References

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