Negative hyperselection of patients with HER2(+) and RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade: The PRESSING-HER2 study Journal Article
| Authors: | Randon, G.; Nakamura, Y.; Yaeger, R.; Lonardi, S.; Cremolini, C.; Elez, E.; Nichetti, F.; Ghelardi, F.; Nasca, V.; Bergamo, F.; Conca, V.; Ros, J.; Bando, H.; Maddalena, G.; Oldani, S.; Prisciandaro, M.; Raimondi, A.; Schrock, A. B.; Agnelli, L.; Walch, H.; Yoshino, T.; Pietrantonio, F. |
| Article Title: | Negative hyperselection of patients with HER2(+) and RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade: The PRESSING-HER2 study |
| Abstract: | Purpose: To demonstrate the negative prognostic impact of a panel of genomic alterations (PRESSING-HER2 panel) and lack of HER2 amplification by next-generation sequencing (NGS) in patients with HER2þ, RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade. Experimental Design: The PRESSING-HER2 panel of HER2 mutations/rearrangements and RTK/MAPK mutations/amplifications was assessed by NGS. HER2 amplification was confirmed by NGS if copy-number variation (CNV) was ≥ 6. With a case–control design, hypothesizing 30% and 5% PRESSING-HER2 positivity in resistant [progression-free survival (PFS) <4 months and no RECIST response] versus sensitive cohorts, respectively, 35 patients were needed per group. Results: PRESSING-HER2 alterations included HER2 mutations/ rearrangements, EGFR amplification, and BRAF mutations and had a prevalence of 27% (9/33) and 3% (1/35) in resistant versus sensitive patients (P 1⁄4 0.005) and 63% predictive accuracy. Overall, HER2 nonamplified status by NGS had 10% prevalence. Median PFS and overall survival (OS) were worse in PRESSING-HER2þ versus negative (2.2 vs. 5.3 months, P < 0.001; 5.4 vs. 14.9 months, P 1⁄4 0.001) and in HER2 nonamplified versus amplified (1.6 vs. 5.2 months, P < 0.001; 7.4 vs. 12.4 months, P 1⁄4 0.157). These results were confirmed in multivariable analyses [PRESSING-HER2 positivity: PFS HR 1⁄4 3.06, 95% confidence interval (CI), 1.40–6.69, P 1⁄4 0.005; OS HR 1⁄4 2.93, 95% CI, 1.32–6.48, P 1⁄4 0.007]. Combining PRESSING-HER2 and HER2 CNV increased the predictive accuracy to 75%. Conclusions: PRESSING-HER2 panel and HER2 nonamplified status by NGS warrant validation as potential predictive markers in this setting. Copyright 2023 The Authors; Published by the American Association for Cancer Research. |
| Keywords: | genetics; mutation; antineoplastic agent; progression free survival; antineoplastic combined chemotherapy protocols; colonic neoplasms; pathology; colorectal neoplasms; colorectal tumor; colon tumor; rectal neoplasms; rectum tumor; progression-free survival; humans; prognosis; human |
| Journal Title: | Clinical Cancer Research |
| Volume: | 30 |
| Issue: | 2 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2024-01-15 |
| Start Page: | 436 |
| End Page: | 443 |
| Language: | English |
| DOI: | 10.1158/1078-0432.Ccr-23-1379 |
| PUBMED: | 37610454 |
| PROVIDER: | scopus |
| PMCID: | PMC10792357 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus |
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