Cancer reports (Hoboken, N.J.) · 2026
Genetic and Clinical Characteristics of Patients With Tumor Mutation Burden-High Unresectable Pancreatic Cancer and the Efficacy of Pembrolizumab Treatment.
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Kai Yugo, Ikezawa Kenji, Kozumi Kazuhiro, Urabe Makiko, Takada Ryoji, Kinomoto Takumi, Masumoto Takanori, Kawabata Masaki, Kishimoto Hiroki, Hosokawa Kana, Mukai Kaori, Nakabori Tasuku, Yamaguchi Yuko, Sugimoto Naotoshi, Ohkawa Kazuyoshi
Аннотация
BACKGROUND: Pembrolizumab is approved for treating patients with advanced solid tumors exhibiting high tumor mutation burden (TMB), including pancreatic cancer. However, owing to the rarity of TMB-high pancreatic cancer, its genetic and clinical characteristics, alongside the therapeutic effectiveness of pembrolizumab, remain unclear.
AIMS: To investigate the characteristics and assess the effectiveness of pembrolizumab in this patient population.
METHODS AND RESULTS: We retrospectively reviewed data of 293 patients with unresectable or recurrent pancreatic cancer who underwent comprehensive genomic profiling at our hospital between December 2019 and April 2023. TMB-high was observed in 13 cases (4.4%), including four patients with microsatellite instability-high (MSI-H) (1.4%). Two patients exhibited germline BRCA2 mutations: one with adenocarcinoma and the other with acinar cell carcinoma. Germline mutations in MLH1 and MSH6 were each identified in one case, both exhibiting MSI-H plus TMB-high. The frequency of pathogenic mutations in KRAS, TP53, CDKN2A, and SMAD4 was notably high. KRAS mutations were detected in 12 of the 13 patients (92.3%). Pembrolizumab was administered to six patients, yielding an objective response rate of 33.3% and a disease control rate of 66.7%. Among the three patients with MSI-H plus TMB-high, two achieved partial response, and the median progression-free survival for all three patients was 227 days. Among the three microsatellite stable (MSS) plus TMB-high cases, two exhibited stable disease, and the median progression-free survival for all three patients was 90 days.
CONCLUSION: The frequency of TMB-high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI-H plus TMB-high while also exhibiting some efficacy in patients with MSS plus TMB-high.
AIMS: To investigate the characteristics and assess the effectiveness of pembrolizumab in this patient population.
METHODS AND RESULTS: We retrospectively reviewed data of 293 patients with unresectable or recurrent pancreatic cancer who underwent comprehensive genomic profiling at our hospital between December 2019 and April 2023. TMB-high was observed in 13 cases (4.4%), including four patients with microsatellite instability-high (MSI-H) (1.4%). Two patients exhibited germline BRCA2 mutations: one with adenocarcinoma and the other with acinar cell carcinoma. Germline mutations in MLH1 and MSH6 were each identified in one case, both exhibiting MSI-H plus TMB-high. The frequency of pathogenic mutations in KRAS, TP53, CDKN2A, and SMAD4 was notably high. KRAS mutations were detected in 12 of the 13 patients (92.3%). Pembrolizumab was administered to six patients, yielding an objective response rate of 33.3% and a disease control rate of 66.7%. Among the three patients with MSI-H plus TMB-high, two achieved partial response, and the median progression-free survival for all three patients was 227 days. Among the three microsatellite stable (MSS) plus TMB-high cases, two exhibited stable disease, and the median progression-free survival for all three patients was 90 days.
CONCLUSION: The frequency of TMB-high was 4.4%, which is slightly higher than that previously reported. Pembrolizumab demonstrated greater efficacy in patients with MSI-H plus TMB-high while also exhibiting some efficacy in patients with MSS plus TMB-high.