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KMID : 0939920200520041135
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대한암학회지
2020 Volume.52 No. 4 p.1135 ~ p.1144
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A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair?Deficient/Microsatellite Instability?High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer
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Kim Jwa-Hoon
Kim Sun-Young
Baek Ji-Yeon
Cha Yong-Jun
Ahn Joong-Bae
Kim Han-Sang
Lee Keun-Wook
Kim Ji-Won
Kim Tae-You
Chang Won-Jin
Park Joon-Oh
Kim Ji-Hun
Kim Jeong-Eun
Hong Yong-Sang
Kim Yeul-Hong
Kim Tae-Won
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Abstract
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Purpose: We evaluated the efficacy and safety of avelumab, an anti-PD-L1 antibody, in patients with metastatic or unresectable colorectal cancer (mCRC) with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H) or POLE mutations.
Materials and Methods: In this prospective, open-label, multicenter phase II study, 33 patients with mCRC harboring dMMR/MSI-H or POLE mutations after failure of ≥1st-line chemotherapy received avelumab 10 mg/kg every 2 weeks. dMMR/MSI-H was confirmed with immunohistochemical staining (IHC) by loss of expression of MMR proteins or polymerase chain reaction (PCR) for microsatellite sequences. POLE mutation was confirmed by next-generation sequencing (NGS). The primary endpoint was the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors ver. 1.1.
Results: The median age was 60 years, and 78.8% were male. Thirty patients were dMMR/MSI-H and three had POLE mutations. The ORR was 24.2%, and all of the responders were dMMR/MSI-H. For 21 patients with MSI-H by PCR or NGS, the ORR was 28.6%. At a median follow-up duration of 16.3 months, median progression-free survival and overall survival were 3.9 and 13.2 months in all patients, and 8.1 months and not reached, respectively, in patients with MSI-H by PCR or NGS. Dose interruption and discontinuation due to treatment-related adverse events occurred in four and two patients, respectively, with no treatment-related deaths.
Conclusion: Avelumab displayed antitumor activity with manageable toxicity in patients with previously treated mCRC harboring dMMR/MSI-H. Diagnosis of dMMR/MSI-H with PCR or NGS could be complementary to IHC to select patients who would benefit from immunotherapy.
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KEYWORD
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Colorectal neoplasms, Mismatch repair deficiency, Microsatellite instability, POLE mutation, Avelumab
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