Outcomes and a prognostic classifier in patients with microsatellite instability-high metastatic gastric cancer receiving PD-1 blockade.
J Immunother Cancer
; 11(6)2023 06.
Article
em En
| MEDLINE
| ID: mdl-37277193
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Adenocarcinoma
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
J Immunother Cancer
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália