1063P - Differential tumor responses are a poor prognostic factor in patients receiving immune checkpoint inhibitors

Background

Radiological assessment of tumor response to immune checkpoint inhibitors (ICI) can be challenging. This retrospective study aimed to identify patterns of dissociated response (DR) to treatment and correlate them to clinical outcome.

Methods

We analyzed CT imaging data from 257 metastatic patients receiving ICI, who underwent imaging at baseline and on-therapy. Up to 10 lesions per organ were segmented using 3DSlicer at baseline and best response by RECIST 1.1. Changes in tumor diameter from baseline to best response were assessed. DR was defined as the co-existence of lesions with an increase and decrease in diameter (-10% / +10%, based on an internal variability study) or a decrease in diameter of one or more lesions with the appearance of new lesions.

Results

This cohort comprised 257 patients (63% male) with different tumor types including lung, melanoma, breast, colorectal and others. According to the RECIST classification 6.6% (17/257) of patients had CR, 20.2% (52/257) PR, 35.4% (91/257) SD and 37.7% (97/257) PD. DR was identified in 13% (34/257) patients at the time of best response by RECIST. 21/34 patients with DR were classified as SD or PR by RECIST1.1; their overall survival was significantly lower than SD/PR patients without DR (n=140) (median OS 11.96 vs 20.01 months, p-value <0.02). The incidence of DR was not associated with tumor type or burden of disease. A higher number of organs affected at baseline was significantly associated with presence of DR (p<0.001). Liver metastasis were a poor prognostic factor irrespective of DR (median OS 7.3 vs 15 months, p-value<0.005).

Conclusions

Dissociated responses to ICI are common across tumor types and associate with poor clinical outcome. DR probably reflects underlying intra-patients' biological heterogeneity both at the tumor and tumor micro-environment level and can be captured through individual lesion assessment in standard of care imaging.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

RPL is supported by “la Caixa” Foundation, a CRIS Foundation Talent Award (TALENT19-05), the FERO Foundation, the Instituto de Salud Carlos III-Investigación en Salud (PI18/01395 and PI21/01019) and the Prostate Cancer Foundation (18YOUN19).

Disclosure

C. Tozzi: Financial Interests, Advisory Board: VHIO. M. Vieito Villar: Non-Financial Interests, Principal Investigator: Roche, BMS, Taiho, Hutchinson Pharma, Novartis, Mundipharma, Enterome, Debiopharm. I. Braña: Financial Interests, Personal, Advisory Board: Achilles Therapeutics, Bristol Myers Squibb, Cancer Expert Now, eTheRNA Immunotherapies, Merck Serono, Merck Sharp & Dohme (MSD), Rakuten Pharma, Boehringer Ingellheim, PCI Biotech, Guidepoint; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme (MSD), Roche; Financial Interests, Institutional, Local PI: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, GSK, Gliknik, Incyte, ISA pharmaceuticals, Janssen Oncology, Kura, Merck Serono, Debiopharm, Merck Sharp & Dohme (MSD), Nanobiotix, Novartis, Northern Biologics, Regeneron, Pfizer, Seattle Genetics, Shattuck Labs, VCN Biosciences, Roche, Immutep, MacroGenics, Sanofi, PharmaMar, Odonate Therapeutics, Bicycle Therapeutics, Dragonfly therapeutics, Gilead; Non-Financial Interests, Principal Investigator, Basket of baskets: Cancer Core Europe; Non-Financial Interests, Member, Head and Neck Group: EORTC; Non-Financial Interests, Member: SEOM, ASCO. E. Garralda: Financial Interests, Personal, Advisory Board: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Alkermes, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, F-Star Therapeutics, Sanofi, Incyte; Financial Interests, Personal, Invited Speaker: MSD, Lilly, Roche, Thermo Fisher, Novartis, Seagen; Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Institutional, Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho; Financial Interests, Institutional, Research Grant: BeiGene, Janssen. R. Perez Lopez: Financial Interests, Personal, Full or part-time Employment, VHIO staff (team leader of the Radiomics Group): VHIO; Financial Interests, Institutional, Research Grant, Co-PI of 3 research studies.: AstraZeneca; Financial Interests, Institutional, Research Grant, PI of a research study.: Roche. All other authors have declared no conflicts of interest.