A Phase II Study of Avelumab Monotherapy in Patients with Mismatch Repair-Deficient/Microsatellite Instability-High or POLE-Mutated Metastatic or Unresectable Colorectal Cancer

• Published in: Cancer research and treatment Vol. 52; no. 4; pp. 1135 - 1144
• Main Authors: 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, Jihun, Kim, Jeong Eun, Hong, Yong Sang, Kim, Yeul Hong, Kim, Tae Won
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Cancer Association 01.10.2020; 대한암학회
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antineoplastic Agents, Immunological - administration & dosage; Antineoplastic Agents, Immunological - adverse effects; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; DNA Mismatch Repair; DNA Polymerase II - genetics; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Microsatellite Instability; Middle Aged; Mutation; Original; Poly-ADP-Ribose Binding Proteins - genetics; Progression-Free Survival; Prospective Studies; 의학일반; Avelumab; POLE mutation; Mismatch repair deficiency; Colorectal neoplasms; Microsatellite instability
• ISSN: 1598-2998; 2005-9256; 2005-9256
• DOI: 10.4143/crt.2020.218

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. 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. 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. 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.