Abstract 75P
Background
Clinical trials have demonstrated the efficacy of targeted therapy in HER2+ pre-treated mCRC, supporting HER2 as a predictive biomarker in mCRC. The prognostic role of HER2 status in mCRC is less clear as mixed outcomes have been reported in patients with HER2+ mCRC treated with non-HER2 targeted therapies. This study assessed the impact of HER2 status on real-world overall survival (rwOS) and outcomes of later line therapy in patients with mCRC.
Methods
This retrospective cohort study included patients with mCRC diagnosed Jan 1 2011 to Jan 1 2023 from the US-based de-identified Flatiron Health-Foundation Medicine CRC Clinico-Genomic Database who underwent comprehensive genomic profiling and did not receive HER2-targeted therapy. Outcomes, evaluated based on HER2 status (HER2+ defined as documented ERBB2 amplification), included rwOS from start of first-line therapy and time to next treatment (rwTTNT) from start of regorafenib or trifluridine/tipiracil, two standard of care later line therapies. Time to event outcomes were estimated by Kaplan-Meier and compared with log-rank test. Associations between exposures and outcomes were estimated with Cox proportional hazard models.
Results
The rwOS cohort included 7121 patients: 6948 (97.6%) HER2- and 173 (2.4%) HER2+. Baseline characteristics were generally balanced between groups (Table). Median (95% CI) rwOS was 29.6 (28.8–30.3) months for HER2- patients and 30.6 (24.4–38.5) months for HER2+ patients (HR [95% CI]: 1.17 [0.96–1.43]). 1336 patients received regorafenib or trifluridine/tipiracil (most [82.4%] in third line or later): 1301 (97.4%) HER2- and 35 (2.6%) HER2+. Median rwTTNT (95% CI) was 3.9 (3.8–4.2) months for HER2- patients and 3.9 (3.2–5.9) months for HER2+ patients (HR [95% CI]: 1.08 [0.75–1.56]). Table: 75P
Baseline characteristics (rwOS cohort)
| Characteristic | Overall (N = 7121) | HER2- (n = 6948) | HER2+ (n = 173) |
| Age (y) at index, median (IQR) | 61 (52, 70) | 61 (52, 70) | 60 (50, 67) |
| Female, n (%) | 3281 (46) | 3212 (46) | 69 (40) |
| Index therapy, n (%) | |||
| Anti-VEGF | 3754 (53) | 3687 (53) | 67 (39) |
| Anti-EGFR | 592 (8) | 563 (8) | 29 (17) |
| Tumor location, n (%) | |||
| Right sided | 1612 (23) | 1590 (23) | 22 (13) |
| Left sided | 2670 (37) | 2599 (37) | 71 (41) |
| Both sided | 275 (4) | 270 (4) | 5 (3) |
| Other / Unknown | 2564 (36) | 2489 (36) | 75 (43) |
| Biomarker status, n (%) | |||
| BRAF mutation negative | 6438 (90) | 6269 (90) | 169 (98) |
| KRAS mutation negative | 3563 (50) | 3423 (49) | 140 (81) |
| NRAS mutation negative | 6793 (95) | 6623 (95) | 170 (98) |
| MSI microsatellite stable | 5858 (82) | 5710 (82) | 148 (86) |
Conclusions
HER2 status did not appear to impact rwOS or rwTTNT of later line therapies. These findings do not support a prognostic role for HER2 status in mCRC.
Editorial acknowledgement
Editorial support was provided by Yasmin Lau, of Curo, a division of Envision Pharma Group, and funded by Seagen Inc, which was acquired by Pfizer in December 2023.
Legal entity responsible for the study
This study was sponsored by Seagen Inc, which was acquired by Pfizer in December 2023 in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.
Funding
Pfizer Inc.
Disclosure
N. Starling: Financial Interests, Invited Speaker: Amgen, GSK, Lilly, Merck Serono, MSD Oncology, Novartis, Pierre Fabre, Pfizer Inc, Servier; Financial Interests, Advisory Role: AstraZeneca, MSD Oncology, Novartis Pharmaceuticals UK Ltd., Pfizer Inc.; Financial Interests, Funding: AstraZeneca, Bristol Myers Squibb, Pfizer Inc, EMD Serono; Financial Interests, Other, Travel accommodation and expenses: Guardant Health, MSD Oncology; Non-Financial Interests, Other, Uncompensated relationships: Guardant Health. J. Snider, C. Cho-Phan, J. Wang: Financial Interests, Full or part-time Employment: Flatiron Health Inc, which is an independent member of the Roche group; Financial Interests, Stocks/Shares: Roche. P. Martin, C. Simon: Financial Interests, Full or part-time Employment: Pfizer Ltd.; Financial Interests, Stocks/Shares: Pfizer Ltd. K. Bartley: Financial Interests, Full or part-time Employment: Pfizer Inc; Financial Interests, Stocks/Shares: Pfizer Inc.