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
- Oh, C.R.; Kim, J.E.; Hong, Y.S.; Kim, S.Y.; Ahn, J.B.; Baek, J.Y.; Lee, M.-A.; Kang, M.J.; Cho, S.H.; Beom, S.-H.; Kim, T.W.
- Issue Date
- 15-Jun-2022
- Publisher
- John Wiley and Sons Inc
- Keywords
- colorectal cancer; durvalumab; microsatellite instability; mismatch repair deficiency; POLE mutation
- Citation
- International Journal of Cancer, v.150, no.12, pp 2038 - 2045
- Pages
- 8
- Journal Title
- International Journal of Cancer
- Volume
- 150
- Number
- 12
- Start Page
- 2038
- End Page
- 2045
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/61280
- DOI
- 10.1002/ijc.33966
- ISSN
- 0020-7136
1097-0215
- 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. © 2022 UICC.
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