期刊
JAMA ONCOLOGY
卷 6, 期 7, 页码 1068-1071出版社
AMER MEDICAL ASSOC
DOI: 10.1001/jamaoncol.2020.1046
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Question What are the outcomes in patients with advanced, microsatellite instability-high (MSI-H) cancers following treatment with immune checkpoint inhibitors (ICIs)? Findings In patients with MSI-H advanced cancers, even in the pretreated setting, the pooled response rate and disease control rate of ICIs were 41.5% and 62.8%, respectively. The pooled 1- and 2-year OS were 75.6% and 56.5%, respectively. Meaning In patients with MSI-H cancer, treatment with ICIs was associated with high activity; MSI status may have a high predictive value for the benefit of immunotherapy. Importance The mismatch repair (MMR) pathway plays a crucial role in repairing DNA replication errors in normal and cancer cells. Defects in DNA MMR proteins that determine the microsatellite instability-high (MSI-H) condition lead to the accumulation of mutations and the generation of neoantigens, which may stimulate the antitumor immune response. Clinical trials have demonstrated that MSI-H status is associated with long-term benefit in patients treated with immune checkpoint inhibitors (ICIs). Objective To evaluate the activity of ICIs in terms of overall response rate (ORR), disease control rate (DCR), overall survival (OS), and progression-free survival (PFS) in patients with MSI-H cancers. Data Sources Published articles that evaluated ICIs in the treatment of advanced MSI-H tumors from inception to December 2019 were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Study Selection Prospective or retrospective studies, published in the English language, providing outcome data with ICIs in patients with MSI-H cancer were selected. Data Extraction and Synthesis Author and year of publication, type of studies, diseases included, median follow up, type of ICI, median OS ,and PFS, ORR, DCR and 1-, 2-, and 3-year OS were retrieved. Analysis was performed in December 2019. Main Outcome and Measures The primary outcome of interest was ORR. Secondary end points were median PFS, median OS, pooled rate of patients alive at 1, 2 ,and 3 years, and pooled rate of patients that attained disease control rate ([DCR] calculated as the sum of stable disease rate and ORR). Results Overall, 939 patients (14 studies) were analyzed mainly in pretreated settings. The pooled ORR was 41.5% (95% CI, 34.9%-48.4%). The pooled DCR was 62.8% (95% CI, 54.5%-70.3%). Pooled median PFS was 4.3 months (95% CI, 3-6.8 months). The pooled median OS was 24 months (95% CI, 20.1-28.5 months). The pooled 1- and 2-year OS were 75.6% (95% CI, 61.8%-85.5%) and 56.5% (95% CI, 46%-66.4%), respectively. Because only 1 study provided 3-year OS data, a formal pooled analysis for 3 years was not possible. Conclusions and Relevance In this meta-analysis of patients with pretreated MSI-H cancer, ICIs were associated with high activity independent of tumor type and drug used. Among molecular biomarkers for selection of treatment, MMR proteins may have a predictive value for the activity of immunotherapy. This systematic review and meta-analysis evaluates the association of immune checkpoint inhibitor treatment with overall response rate, disease control rate, overall survival, and progression-free survival in patients with microsatellite instability-high cancers.
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