Clinical and Molecular Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Esophagogastric Cancer
| العنوان: | Clinical and Molecular Predictors of Response to Immune Checkpoint Inhibitors in Patients with Advanced Esophagogastric Cancer |
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| المؤلفون: | Megan Greally, Luis A. Diaz, David B. Solit, Yaelle Tuvy, Laura H. Tang, David P. Kelsen, David H. Ilson, Geoffrey Y. Ku, Michael F. Berger, Jaclyn F. Hechtman, Marinela Capanu, Foysal Daian, Ritika Kundra, Nikolaus Schultz, Joanne F. Chou, Walid K. Chatila, Yelena Y. Janjigian, Marc Ladanyi, Matthew Margolis |
| المصدر: | Clinical Cancer Research. 25:6160-6169 |
| بيانات النشر: | American Association for Cancer Research (AACR), 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Oncology, Cancer Research, Esophageal Neoplasms, DNA Mutational Analysis, Programmed Cell Death 1 Receptor, Antibiotics, ECOG Performance Status, Disease, B7-H1 Antigen, Antineoplastic Agents, Immunological, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, CTLA-4 Antigen, Aged, 80 and over, biology, Middle Aged, Prognosis, Progression-Free Survival, 030220 oncology & carcinogenesis, Female, Esophagogastric Junction, Antibody, Adult, medicine.medical_specialty, medicine.drug_class, Article, Young Adult, 03 medical and health sciences, Text mining, Stomach Neoplasms, Esophagogastric cancer, Internal medicine, Biomarkers, Tumor, medicine, Humans, In patient, Response Evaluation Criteria in Solid Tumors, Aged, Retrospective Studies, business.industry, Cancer, medicine.disease, 030104 developmental biology, Mutation, biology.protein, business, Follow-Up Studies |
| الوصف: | 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 = 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. |
| تدمد: | 1557-3265 1078-0432 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c5cbaf58063babb4b3bbba16cfbf5c4eTest https://doi.org/10.1158/1078-0432.ccr-18-3603Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c5cbaf58063babb4b3bbba16cfbf5c4e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15573265 10780432 |
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