Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade Journal Article
| Authors: | Randon, G.; Aoki, Y.; Cohen, R.; Provenzano, L.; Nasca, V.; Klempner, S. J.; Maron, S. B.; Cerantola, R.; Chao, J.; Fornaro, L.; Ferrari Bravo, W.; Ghelardi, F.; Ambrosini, M.; Manca, P.; Salati, M.; Kawazoe, A.; Zhu, V.; Cowzer, D.; Genovesi, V.; Lonardi, S.; Shitara, K.; André, T.; Pietrantonio, F. |
| Article Title: | Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade |
| Abstract: | BACKGROUND: Subgroup analyses of randomized trials suggest the superiority of immune checkpoint inhibitor-based therapy over chemotherapy in patients with mismatch-repair deficient (dMMR) and/or microsatellite instability-high (MSI-high) advanced gastric or gastroesophageal junction adenocarcinoma. However, these subgroups are small and studies examining prognostic features within dMMR/MSI-high patients are lacking. METHODS: We conducted an international cohort study at tertiary cancer centers and collected baseline clinicopathologic features of patients with dMMR/MSI-high metastatic or unresectable gastric cancer treated with anti-programmed cell death protein-1 (PD-1)-based therapies. The adjusted HRs of variables significantly associated with overall survival (OS) were used to develop a prognostic score. RESULTS: One hundred and thirty patients were included. At a median follow-up of 25.1 months, the median progression-free survival (PFS) was 30.3 months (95% CI: 20.4 to NA) and 2-year PFS rate was 56% (95% CI: 48% to 66%). Median OS was of 62.5 months (95% CI: 28.4 to NA) and 2-year OS rate was 63% (95% CI: 55% to 73%). Among the 103 Response Evaluation Criteria in Solid Tumors-evaluable patients, objective response rate was 66% and disease control rate 87% across lines of therapy. In the multivariable models, Eastern Cooperative Oncology Group Performance Status of 1 or 2, non-resected primary tumor, presence of bone metastases and malignant ascites were independently associated with poorer PFS and OS. These four clinical variables were used to build a three-category (ie, good, intermediate, and poor risk) prognostic score. Compared with patients with good risk, patients with intermediate risk score had numerically inferior PFS and OS (2-year PFS rate: 54.3% versus 74.5%, HR 1.90, 95% CI: 0.99 to 3.66; 2-year OS rate: 66.8% versus 81.2%, HR 1.86, 95% CI: 0.87 to 3.98), whereas patients with poor risk score had significantly inferior PFS and OS (2-year PFS rate: 10.6%, HR 9.65, 95% CI: 4.67 to 19.92; 2-year OS rate: 13.3%, HR 11.93, 95% CI: 5.42 to 26.23). CONCLUSIONS: Overall outcomes with anti-PD-1-based therapies are favorable in MSI-high gastroesophageal adenocarcinomas. However, within this overall favorable subgroup a more accurate prognostication using baseline clinical characteristics might identify patients at higher risk of rapid disease progression who may deserve intensified immunotherapy combination strategies. © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
| Keywords: | gastrointestinal neoplasms; tumor biomarkers; ctla-4 antigen; programmed cell death 1 receptor; immune checkpoint inhibitors |
| Journal Title: | Journal for ImmunoTherapy of Cancer |
| Volume: | 11 |
| Issue: | 6 |
| ISSN: | 2051-1426 |
| Publisher: | Biomed Central Ltd |
| Date Published: | 2023-06-01 |
| Start Page: | e007104 |
| Language: | English |
| DOI: | 10.1136/jitc-2023-007104 |
| PUBMED: | 37277193 |
| PROVIDER: | scopus |
| PMCID: | PMC10255232 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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