Synapse - Local therapy for oligoprogression or consolidation in high mutational burden stage 4 colorectal cancer treated with PD-1 or PD-L1 blockade

Local therapy for oligoprogression or consolidation in high mutational burden stage 4 colorectal cancer treated with PD-1 or PD-L1 blockade Journal Article

Authors:	Klemen, N. D.; Court, C. M.; Fernandes, M. C.; Walch, H. S.; Chatila, W. K.; Saadat, L. V.; Maron, S.; Crane, C.; Shia, J.; Cercek, A.; Gönen, M.; Schultz, N. D.; Garcia Aguilar, J.; Jarnagin, W. R.; D’Angelica, M. I.
Article Title:	Local therapy for oligoprogression or consolidation in high mutational burden stage 4 colorectal cancer treated with PD-1 or PD-L1 blockade
Abstract:	Background: Immune checkpoint blockade (ICI) of programmed cell death protein 1 (PD-1) or PD-1 ligand (PD-L1) can induce durable responses in patients who have colorectal cancer (CRC) with a high tumor mutational burden (TMB). Two recurring clinical dilemmas show how to manage oligoprogressive disease and stable disease after ICI. Methods: A cohort study was conducted to analyze patients with metastatic CRC who underwent PD-1 or PD-L1 blockade. Tumors were mismatch repair (MMR) deficient or had more than 25 mutations per megabase. Patients were identified who had local therapy (surgery, ablation, or radiotherapy) for one to three sites of progressive disease (PD) or surgery to consolidate SD. The study evaluated clinical and biologic factors associated with patient selection, outcomes, and pathologic response rates. Results: From 2014 to 2020, treatment was administered to 111 patients with ICI. Of these 111 patients, 19 (17%) survived fewer than 6 months, whereas to date, 50 have not had progression of disease. The remaining 42 patients experienced PD, and 16 (38%) were treated with local therapy for oligoprogression. Selection for local therapy was associated with response to ICI. The 2-year progression-free survival (PFS) after local therapy was 62%. Finally, 6 of the 50 patients without PD had consolidation of SD, and 5 had complete or near complete pathologic responses. Conclusions: Oligoprogression, a frequent pattern of failure after ICI, can be managed effectively with local therapy. In contrast, it may not be necessary to consolidate SD for selected patients. Further research is essential to define management algorithms better and to explore heterogeneity in response patterns. © 2022, Society of Surgical Oncology.
Keywords:	adult; cancer survival; controlled study; aged; middle aged; cancer surgery; major clinical study; overall survival; genetics; mutation; patient selection; systemic therapy; cancer patient; cancer radiotherapy; cancer staging; nuclear magnetic resonance imaging; outcome assessment; follow up; metabolism; progression free survival; computer assisted tomography; cohort studies; neoplasm recurrence, local; lung neoplasms; carcinoembryonic antigen; local therapy; cohort analysis; pathology; colorectal neoplasms; lung tumor; colorectal tumor; tumor recurrence; mismatch repair; ligand; ligands; genome; disease exacerbation; ablation therapy; programmed death 1 ligand 1; programmed death 1 receptor; metastatic colorectal cancer; clinical outcome; immune checkpoint inhibitor; genomic mutation; nivolumab; humans; human; male; female; article; pembrolizumab; programmed cell death 1 receptor; durvalumab; b7-h1 antigen; tumor mutational burden; oligoprogression
Journal Title:	Annals of Surgical Oncology
Volume:	29
Issue:	13
ISSN:	1068-9265
Publisher:	Springer
Date Published:	2022-12-01
Start Page:	8373
End Page:	8382
Language:	English
DOI:	10.1245/s10434-022-12095-x
PUBMED:	35930112
PROVIDER:	scopus
PMCID:	PMC9649851
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85135398823&doi=10.1245%2fs10434-022-12095-x&partnerID=40&md5=7f0e4ab087f0a24fb4ef91eba185ad21
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus