Real-World Treatment Patterns in Patients With HER2-Amplified Metastatic Colorectal Cancer: A Clinical-Genomic Database Study
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Background: HER2 amplification (HER2+) occurs in approximately 3% of patients with metastatic colorectal cancer (mCRC). Despite the recent addition of HER2-directed therapies to treatment recommendations in the NCCN Guidelines, until more recently there were no FDA-approved treatments. This study examined real-world treatment patterns in patients with HER2+ mCRC in the United States before and after the emerging awareness of HER2-directed therapies in 2018. Methods: This was a retrospective observational study of patients with HER2+ mCRC from the GuardantINFORM database, which contains claims data for patients with Guardant360 genomic testing results. Patients were aged ≥18 years, were diagnosed with mCRC between January 2014 and September 2020, and had confirmed ERBB2 amplification via the blood-based Guardant360 test. Treatment patterns and real-world time to next treatment (rwTTNT) were evaluated. Results: This study included 142 patients with a median age of 59 years; 31 (21.8%) patients with ERBB2 amplifications also had ERBB2 mutations. Treatment patterns were heterogeneous and evolved over time; before 2018, the most common regimen prescribed after detection of ERBB2 amplification was anti-VEGF therapy with or without chemotherapy (31.6%; n=25), and after 2018, HER2-directed therapies were the most commonly prescribed (36.5%; n=23). Median rwTTNT among the overall cohort was 8.4 months (95% CI, 6.5–10.0); rwTTNT was numerically longer in patients who received HER2-directed therapy compared with those who received non–HER2-directed therapies (11.0 months [95% CI, 6.3–12.3] vs 7.2 months [95% CI, 5.8–9.6]). Conclusions: This real-world study of the largest clinically annotated dataset of patients with HER2+ mCRC showed that many patients do not receive HER2-directed therapy despite its inclusion in NCCN Guidelines, with heterogeneous treatment patterns suggesting that standard of care remains undefined and targeted therapy remains underutilized. Greater awareness of the unmet need in this patient population, together with new effective therapies, will facilitate strategies for improved, targeted treatment approaches.
Submitted September 3, 2022; final revision received March 9, 2023; accepted for publication March 15, 2023.
Author contributions: Study concept and design: All authors. Data analysis: Hsu, Yu, Zhang, Espenschied, Lang. Data interpretation: All authors. Writing—original draft: Strickler, Hsu, Zhang, Bekaii-Saab. Manuscript preparation—review and editing: All authors.
Disclosures: Dr. Strickler has disclosed serving as a principal investigator for AbbVie, Amgen, AStar D3, Bayer, BeiGene, Curegenix, Daiichi-Sankyo, Eli Lilly, Erasca, Leap Therapeutics, Roche/Genentech, and Seagen; and serving on an advisory board for AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Pfizer, Roche/Genentech, Seagen, Takeda, and Viatris. Dr. Hsu has disclosed owning stock in Seagen. Dr. Stecher has disclosed receiving grant/research support from, being employed by, and owning stock/having ownership interest in Seagen. Dr. Siadak has disclosed being employed by and owning stock/having ownership interest in Seagen. Dr. Palanca-Wessels has disclosed receiving grant/research support from Seagen; holding an executive position, serving on a governing board, or being employed by Seagen; and owning stock/ownership interest in Seagen. N. Zhang has disclosed being employed by and owning stock in Guardant Health. C. Espenschied has disclosed being employed by and owning stock in Guardant Health. Dr. Bekaii-Saab has disclosed receiving grant/research support from Seattle Genetics and Pfizer; serving as a consultant for Pfizer, Seattle Genetics, and Merck; and serving on a data safety monitoring board for Merck. The remaining authors have disclosed that they have not received any financial considerations from any person or organization to support the preparation, analysis, results, or discussion of this article.
Funding: This study was sponsored by Seagen Inc., in collaboration with Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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