Abstract 439P
Background
Currently, there are no approved therapies for patients with HER2-amplified (HER2+) mCRC (∼3% of mCRC). This study examined the real-world characteristics and treatment patterns of patients with HER2+ mCRC.
Methods
Patients were identified from 1/2014–9/2020 in the Guardant INFORM™ clinical-genomic database of aggregated US commercial payer claims with Guardant360® (G360) results. Inclusion criteria: age ≥18 years; ERBB2 amplification; ≥1 inpatient or ≥2 outpatient claims with a CRC diagnosis code at baseline; ≥3 months follow up from index (date of G360 report or start of HER2-directed regimen); and confirmed mCRC. Initial treatments received after ERBB2 status confirmation, stratified by an index date pre- and post-2018 (timing of an increased awareness of HER2), were analyzed.
Results
Of 313 patients included, 142 (45.4%) received treatment after G360 profiling. Baseline demographic and clinical characteristics were similar in treated and untreated patients. Median time from mCRC diagnosis to index date was 26.9 months for untreated and 18.2 months for treated patients. Among treated patients, mean age was 59.3 years and 52.8% were male; 19.7% had KRAS mutations and median ERBB2 copy number was 2.9. Pre-2018, VEGF ± chemotherapy was the most common regimen received; use of HER2-directed and EGFR-based regimens was less common (Table). Post-2018, HER2-directed regimens were the most common. Table: 439P
First treatment following HER2+ status confirmation, by time period
| Treatment, n (%) | Entire Cohort (n=142) | Pre-2018 (n=79) | Post-2018 (n=63) |
| VEGF ± chemotherapy | 43 (30.3) | 24 (30.3) | 19 (30.2) |
| HER2 ± chemotherapy | 42 (29.5) | 19 (24.1) | 23 (36.5) |
| Chemotherapy | 29 (20.4) | 17 (21.5) | 12 (19.0) |
| EGFR ± chemotherapy | 14 (9.9) | 10 (12.7) | 4 (6.3) |
| Trifluridine + tipiracil | 6 (4.2) | 2 (2.5) | 4 (6.3) |
| Non-NCCN recommended | 5 (3.5) | 4 (5.1) | 1 (1.6) |
| Regorafenib | 3 (2.1) | 3 (3.8) | 0 (0) |
EGFR, epidermal growth factor receptor; HER2, human epidermal growth factor receptor 2; NCCN, National Comprehensive Cancer Network; VEGF, vascular endothelial growth factor.
Conclusions
Using a unique clinical-genomic dataset, this study highlights the significant unmet need in patients with HER2+ mCRC. Although use of HER2-directed therapies has increased, heterogeneous treatment patterns suggest no clear standard of care. Over half (54.6%) of patients do not receive any systemic treatment following confirmation of HER2 status. Effective therapies and enhanced awareness of the unmet need in this patient population will facilitate improved, targeted treatment strategies.
Clinical trial identification
Editorial acknowledgement
Editorial support was provided by Ann Cameron of Curo, a division of Envision Pharma Group, and funded by Seagen Inc.
Legal entity responsible for the study
Seagen Inc.
Funding
Seagen Inc.
Disclosure
J.H. Strickler: Financial Interests, Personal, Advisory Board: AbbVie; Amgen; AstraZeneca; Bayer; Natera; Pfizer; Seagen; Viatris; Financial Interests, Personal, Other, Consulting: Mereo; Non-Financial Interests, Institutional, Principal Investigator, Local PI: AbbVie; AStar D3; AstraZeneca; Curegenix; Daiichi Sankyo; Leap Therapeutics; Nektar; Roche Genentech; Sanofi; Non-Financial Interests, Institutional, Principal Investigator, Coordinating PI: Amgen; Exelixis; Seagen. L. Hsu: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc.. K. DeBusk: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc.. P. Wright: Non-Financial Interests, Personal, Training, University of Washington/Seagen Inc. post-doctoral fellow: Seagen Inc.. M. Stecher: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc.. M. Siadak: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc.. M..C. Palanca-Wessels: Financial Interests, Personal, Full or part-time Employment: Seagen Inc.; Financial Interests, Personal, Stocks/Shares: Seagen Inc.. J. Yu: Financial Interests, Personal, Full or part-time Employment: Guardant Health Inc.; Financial Interests, Personal, Stocks/Shares, Seattle Genetics: Guardant Health Inc.; Financial Interests, Institutional, Funding: Seagen Inc.. N. Zhang: Financial Interests, Personal, Full or part-time Employment: Guardant Health Inc.; Financial Interests, Personal, Stocks/Shares: Guardant Health Inc.; Financial Interests, Institutional, Funding: Seagen Inc.. C.R. Espenschied: Financial Interests, Personal, Full or part-time Employment: Guardant Health Inc.; Financial Interests, Personal, Stocks/Shares: Guardant Health Inc.; Financial Interests, Institutional, Funding: Seagen Inc.. K. Lang: Financial Interests, Personal, Full or part-time Employment: Guardant Health Inc.; Financial Interests, Personal, Stocks/Shares: Guardant Health Inc.; Financial Interests, Institutional, Funding: Seagen Inc.. T. Bekaii-Saab: Financial Interests, Personal, Advisory Board: Abbie; AstraZeneca; Beigene; Boehringer Ingelheim; Celularity; Daichi Sankyo; Eisai; Exact Science; Janssen; Natera; Sobi; Xilis; Foundation Medicine; Financial Interests, Personal, Other, DSMB: AstraZeneca; Exelixis; Lilly; Financial Interests, Institutional, Advisory Board: Bayer; Genentech; Incyte; Ipsen; Pfizer; Seagen; Financial Interests, Institutional, Other, DSMB: Merck; Financial Interests, Personal, Invited Speaker, DSMB: PanCAN; Financial Interests, Institutional, Research Grant: Abgenomics; Agios; Amgen; Arcus; Arys; Atreca; Bayer; BMS; Celgene; Clovis; Ipsen; Merus; Mirati; Novartis; Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Boston Biomedical; Incyte; Financial Interests, Institutional, Other, Steering Committee Member: Seagen; Non-Financial Interests, Advisory Role: Imugene; Sun Biopharma.