Clinical and molecular predictors of response to immune checkpoint inhibitors in patients with advanced esophagogastric cancer Journal Article
| Authors: | Greally, M.; Chou, J. F.; Chatila, W. K.; Margolis, M.; Capanu, M.; Hechtman, J. F.; Tuvy, Y.; Kundra, R.; Daian, F.; Ladanyi, M.; Kelsen, D. P.; Ilson, D. H.; Berger, M. F.; Tang, L. H.; Solit, D. B.; Diaz, L. A. Jr; Schultz, N.; Janjigian, Y. Y.; Ku, G. Y. |
| Article Title: | Clinical and molecular predictors of response to immune checkpoint inhibitors in patients with advanced esophagogastric cancer |
| Abstract: | Purpose: Immune checkpoint inhibitors (ICI) are effective in only a minority of patients with esophagogastric cancer (EGC). Here, we aimed to identify predictors of durable clinical benefit to ICI in EGC. Experimental Design: Patients with advanced EGC treated with ICIs at Memorial Sloan Kettering Cancer Center (New York, NY) were identified. Clinicopathologic variables were assessed. In patients profiled by MSK-IMPACT–targeted sequencing, outcomes were correlated with tumor genomic features. Results: One-hundred sixty-one patients were treated with ICIs (110 with anti–PD-1/PD-L1 antibodies and 51 with anti–CTLA-4 and PD-1/PD-L1 antibodies). The median progression-free survival (PFS) and overall survival (OS) were 1.7 and 4.9 months, respectively. Greater number of disease sites (3), liver metastases, treatment with 3 prior therapies and ECOG performance status 2 were associated with poorer PFS and OS. Patients treated with combination ICI and those with PD-L1–positive tumors had improved outcomes. There was no difference in outcomes between patients treated with antibiotics during or in the 2 months preceding ICI treatment versus those who were not. Occurrence of irAEs was associated with improved OS. In genomically profiled tumors (n 1⁄4 89), survival was associated with increasing tumor mutation burden (TMB). However, in multivariable analyses and when microsatellite unstable (MSI) patients were excluded, a significant association was no longer observed. Conclusions: In patients with advanced EGC, heavily pretreated patients, those with high-volume disease and/or poor PS were less likely to benefit from ICI. irAEs were associated with improved OS. TMB correlated with improved survival, but this association was not observed when MSI-high patients were excluded. © 2019 American Association for Cancer Research. |
| Journal Title: | Clinical Cancer Research |
| Volume: | 25 |
| Issue: | 20 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2019-10-15 |
| Start Page: | 6160 |
| End Page: | 6169 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-18-3603 |
| PUBMED: | 31337644 |
| PROVIDER: | scopus |
| PMCID: | PMC6905384 |
| DOI/URL: | |
| Notes: | Source: Scopus |
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