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Phase II study of durvalumab monotherapy in patients with previously treated microsatellite instability-high/mismatch repair-deficient or POLE-mutated metastatic or unresectable colorectal cancer

Authors
 Chung Ryul Oh  ;  Jeong Eun Kim  ;  Yong Sang Hong  ;  Sun Young Kim  ;  Joong Bae Ahn  ;  Ji Yeon Baek  ;  Myung-Ah Lee  ;  Myoung Joo Kang  ;  Sang Hee Cho  ;  Seung-Hoon Beom  ;  Tae Won Kim 
Citation
 INTERNATIONAL JOURNAL OF CANCER, Vol.150(12) : 2038-2045, 2022-06 
Journal Title
INTERNATIONAL JOURNAL OF CANCER
ISSN
 0020-7136 
Issue Date
2022-06
MeSH
Antibodies, Monoclonal ; Colorectal Neoplasms* / drug therapy ; Colorectal Neoplasms* / genetics ; Colorectal Neoplasms* / pathology ; DNA Mismatch Repair ; Humans ; Microsatellite Instability* ; Prospective Studies
Keywords
POLE mutation ; colorectal cancer ; durvalumab ; microsatellite instability ; mismatch repair deficiency
Abstract
The aim of our study is to evaluate the clinical efficacy of durvalumab in patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) or polymerase epsilon (POLE)-mutated metastatic or unresectable colorectal cancer (mCRC) who had disease progression after standard chemotherapy. This prospective, open-label, multicenter, phase II study enrolled patients with mCRC harboring MSI-H/dMMR or POLE mutations treated with at least one prior line of therapy. The participants received durvalumab (1500 mg) every 4 weeks intravenously. The primary endpoint was the objective response rate (ORR). Of the 33 patients, 30 had MSI-H/dMMR and 3 had POLE-mutated microsatellite stable (MSS) CRC. With a median follow-up duration of 11.2 months (95% confidence interval [CI]: 7.3-15.0), the ORR was 42.4% (95% CI: 25.5-60.8). Among three patients with POLE-mutated CRC, one patient who had an exonuclease domain mutation (EDM) achieved an objective response, but the others with mutations in the non-exonuclease domain had progressive disease. Overall, the median duration of response was not reached and 85.7% of the responses were ongoing at data cutoff. The progression-free survival rate of 12 months was 58.2% (95% CI: 39.0-73.1) and the 12-month overall survival rate was 68.3% (95% CI: 48.8-81.7). Grade 3 treatment-related adverse events occurred in 36.4% of the patients and were manageable. In conclusion, durvalumab showed promising clinical activity with encouraging response rates and satisfactory survival outcomes in mCRC patients with MSI-H/dMMR or POLE EDM. In patients with POLE-mutated mCRC, clinical response to durvalumab may be restricted to those with EDM.
Full Text
https://onlinelibrary.wiley.com/doi/10.1002/ijc.33966
DOI
10.1002/ijc.33966
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Beom, Seung Hoon(범승훈) ORCID logo https://orcid.org/0000-0001-7036-3753
Ahn, Joong Bae(안중배) ORCID logo https://orcid.org/0000-0001-6787-1503
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191560
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