Circulating tumor DNA-guided treatment with pertuzumab plus trastuzumab for HER2-amplified metastatic colorectal cancer: a phase 2 trial

Journal article

Background: Despite recent metastatic colorectal cancer (mCRC) therapeutic innovations a comprehensive synthesis of patient outcome and risk-benefit assessment of phase 1/2 trials is missing. The aim of this meta-analysis is to assess efficacy, safety, and trends over time for phase 1 and 2 mCRC trials by examining clinical benefit rate (CBR), overall response rate (ORR), grade 3 or higher adverse events (AE), and discontinuation due to AE. Methods: The PRISMA guidelines were followed. We searched PubMed and Embase for publications of phase 1/2 trials between 2010–2021. Trials reporting on new therapies for treatment-refractory mCRC were included. Results: The search strategy yielded 4175 unique reports, of which 258 publications were eligible. These publications report data of 277 unique treatment arms. Overall ORR was 6 %, CBR was 27 % in phase 1 % and 36 % in phase 2 trials. CBR increased from 23 % in 2010–2012 to 42 % in 2019–2021. Compared to 2010–2012, trials in 2019–2021 more often tested immunomodulators (4 % vs 23 %), included molecularly preselected populations (4 % vs 38 %) and younger patients (median age<60 44 % vs 66 %). Grade 3 + AE occurred in 35 % of patients, most frequently in trials investigating targeted treatments. Conclusions: Treatment efficacy in phase 1/2 trials is modest but improved from 2010 to 2021. This improvement is accompanied by a shift towards testing in a younger, fitter, and more strictly molecularly preselected population, as well as an increased focus on targeted and immunotherapies

Authors: Nakamura, Y; Okamoto, W; Kato, T; Esaki, T; Kato, K

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Medicine
• Volume: 27
• Issue: 11
• Pages: 1899-1903
• Publication date: 2021-11-11
• DOI: 10.1038/s41591-021-01553-w
• EISSN: 1546-170X
• ISSN: 1078-8956
• Language: English
• Keywords: Oncology; Trastuzumab; Pertuzumab; Genotype; Genotyping; Biology; Clinical endpoint; Internal medicine; Cancer; Medicine; Colorectal cancer; Breast cancer; Clinical trial; Cetuximab; Population