AI Article Synopsis
- * High gene expression was linked to improved progression-free survival (PFS) and overall survival (OS), with cetuximab showing a survival advantage over bevacizumab in patients with high expression levels, while the opposite was true for low expression levels.
- * The study concluded that tumor gene expression is both prognostic and predictive, suggesting that measuring this expression can help tailor treatment, with patients having low expression potentially benefiting more from bevacizumab therapy.
Article Abstract
Purpose: The phase III Cancer and Leukemia Group B (CALGB)/SWOG 80405 trial found no difference in overall survival (OS) in patients with metastatic colorectal cancer receiving first-line chemotherapy in combination with either bevacizumab or cetuximab. We investigated the potential prognostic and predictive value of amplification and gene expression using next-generation sequencing (NGS) and NanoString data.
Patients And Methods: Primary tumor DNA from 559 patients was profiled for amplification by NGS (FoundationOne CDx). Tumor tissue from 925 patients was tested for NanoString gene expression using an 800-gene panel. OS and progression-free survival (PFS) were the time-to-event end points.
Results: High expression (dichotomized at median) was associated with longer PFS (11.6 10 months, = .012) and OS (32 25.3 months, = .033), independent of treatment. An OS benefit for cetuximab versus bevacizumab was observed in the high expression group ( = .02), whereas a worse PFS for cetuximab was seen in the low-expression group ( = .019). When modeled as a continuous variable, increased expression was associated with longer OS (hazard ratio [HR], 0.83 [95% CI, 0.75 to 0.93]; adjusted = .0007) and PFS (HR, 0.82 [95% CI, 0.74 to 0.91]; adjusted = .0002), reaching a plateau effect after the median. In patients with expression lower than median, treatment with cetuximab was associated with worse PFS (HR, 1.38 [95% CI, 1.12 to 1.71]; adjusted = .0027) and OS (HR, 1.28 [95% CI, 1.02 to 1.59]; adjusted = .03) compared with that with bevacizumab. A significant interaction between expression and the treatment arm was observed for OS ( = .017), PFS ( = .048), and objective response rate ( = .001).
Conclusion: gene expression was prognostic and predictive in CALGB/SWOG 80405. tumor expression may inform treatment selection for patients with low favoring bevacizumab- versus cetuximab-based therapies.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11240881 | PMC |
| http://dx.doi.org/10.1200/JCO.23.01507 | DOI Listing |
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