ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Negative Hyperselection of Patients with HER2+ and RAS Wild-Type Metastatic Colorectal Cancer Receiving Dual HER2 Blockade: the PRESSING-HER2 Study.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 11 citations in OpenAlex.
- Trastuzumab Plus Pertuzumab Versus Cetuximab Plus Irinotecan in Patients WithJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
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- Diverse ERBB2/ERBB3 Activating Alterations and Coalterations Have Implications for HER2/3-Targeted Therapies across Solid Tumors.Cancer research communications · 2025Article
- Case Report: T-Dxd plus bevacizumab in a patient with brain metastases from rectal cancer with HER2 amplification.Frontiers in oncology · 2025Article
- Advances in Precision Medicine Approaches for Colorectal Cancer: From Molecular Profiling to Targeted Therapies.ACS pharmacology & translational science · 2024Review
- PRESSING Need of Precision Care in HER2-Positive Colorectal Cancer: The ELEPHANT in the Room.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
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22 authors at 9 institutions in 6 countries.
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Abstract
purposeTo 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 HER2+, RAS wild-type metastatic colorectal cancer receiving dual HER2 blockade. EXPERIMENTAL
designThe 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.
resultsPRESSING-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 = 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-HER2+ versus negative (2.2 vs. 5.3 months, P < 0.001; 5.4 vs. 14.9 months, P = 0.001) and in HER2 nonamplified versus amplified (1.6 vs. 5.2 months, P < 0.001; 7.4 vs. 12.4 months, P = 0.157). These results were confirmed in multivariable analyses [PRESSING-HER2 positivity: PFS HR = 3.06, 95% confidence interval (CI), 1.40-6.69, P = 0.005; OS HR = 2.93, 95% CI, 1.32-6.48, P = 0.007]. Combining PRESSING-HER2 and HER2 CNV increased the predictive accuracy to 75%.
conclusionsPRESSING-HER2 panel and HER2 nonamplified status by NGS warrant validation as potential predictive markers in this setting. See related commentary by Raghav et al., p. 260.
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