Efficacy of immune checkpoint inhibitors for gastrointestinal cancers with SWI/SNF complex genetic alterations

Autor: Akinobu Nakata, Yukiya Narita, Ryosuke Kumanishi, Taiko Nakazawa, Takatsugu Ogata, Yuki Matsubara, Hiroyuki Kodama, Kazunori Honda, Toshiki Masuishi, Hiroya Taniguchi, Shigenori Kadowaki, Masashi Andoh, Rui Yamaguchi, Masahiro Tajika, Kei Muro
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:346-346
ISSN: 1527-7755
0732-183X
Popis: 346 Background: SWI/SNF chromatin-remodeling complex is encoded by multi-gene families that are recurrently mutated in cancer. Previous studies reported that tumors harboring SWI/SNF complex genetic alterations (GA) are sensitive to immune checkpoint inhibitors (ICIs), but the clinical significance of SWI/SNF complex GA in patients with gastrointestinal cancers (GICs) is unclear. Methods: We reviewed patients with metastatic GICs who underwent comprehensive genomic profiling (CGP) and received ICIs at our institution between July 2014–June 2021. SWI/SNF complex GA were defined as ARID1A, ARID1B, ARID2, PBRM1, SMARCA4, and SMARCB1 alterations. Results: Of 292 patients receiving CGP, 136 patients received ICIs, of which 10 (7.4%) had SWI/SNF GA, including 8 ARID1A (5.9%), 1 ARID2 (0.7%) and 2 SMARCA4 (1.5%) alterations. The subjects included 50 esophageal cancers, 84 gastric cancers, and 2 small intestine cancers. The patients with SWI/SNF complex GA had significantly higher proportions of microsatellite instability-high ( p = 0.004) and lower proportions of esophageal cancer ( p = 0.002), compared with patients without SWI/SNF complex GA. During the median follow-up time of 7.5 months (M), the median overall survival (OS), time-to-treatment failure (TTF), and progression-free survival (PFS) in all patients was 13.2 M ([95% confidence interval [CI] 7.7-21.8 M), 2.2 M (95%CI, 1.8-2.5 M), and 2.3 M (95%CI, 1.9-2.8 M), respectively. The patients with SWI/SNF complex GA had better OS (median, not reached vs 10.3 M; hazard ratio [HR], 0.40 [95% confidence interval [CI] 0.19–0.86]; p = 0.019) than those without SWI/SNF complex GA. The patients with SWI/SNF complex GA tended to have longer TTF (median, 4.7 M vs 2.1 M; HR, 0.67 [95%CI 0.38–1.17]; p = 0.16) and PFS (median, 5.4 M vs 2.2 M; HR, 0.70 [95%CI 0.39–1.27], p = 0.24) than those without SWI/SNF GA. The objective response rate (ORR) and disease control rate (DCR) in all patients was 13.2% (95%CI, 8.0-20.1) and 40.4% (95%CI, 32.1-49.2), respectively. The ORR and DCR of patients with SWI/SNF complex GA tended to be higher than those without SWI/SNF complex GA (ORR, 30.0% vs 11.9%; p = 0.13: DCR, 70.0% vs 38.1%; p = 0.09), with 1 complete response and 2 partial responses in the patients with SWI/SNF complex GA. Conclusions: The patients with GICs who had SWI/SNF complex GA were more likely to benefit from ICI therapy, suggesting that novel ICI-containing chemotherapies targeting SWI/SNF complex GA are needed for GICs.[Table: see text]
Databáze: OpenAIRE
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