Notch1 and CREBBP Co-Mutations Affect Adjuvant Therapy Benefit in EGFR-Mutated NSCLC

What is it about?

The IMPACT study compared adjuvant gefitinib with cisplatin plus vinorelbine in completely resected EGFR-mutated non-small cell lung cancer. Although the primary endpoint of disease-free survival was not met, the study searched for molecular predictors of adjuvant gefitinib efficacy. Frequent somatic mutations included tumor protein p53, CUB and Sushi multiple domains 3, and NOTCH1. Multivariate analysis showed that NOTCH1 co-mutation was a significant poor prognostic factor for overall survival in the gefitinib group, while CREBBP co-mutation was a poor prognostic factor for disease-free survival and overall survival in the cis/vin group. In patients with NOTCH1 co-mutations, the gefitinib group had a shorter overall survival than the cis/vin group, with a significant interaction. In patients with CREBBP co-mutations, the gefitinib group had a longer disease-free survival than the cis/vin group, with a significant interaction. The findings suggest that NOTCH1 and CREBBP mutations might predict poor outcomes in patients treated with gefitinib and cis/vin, respectively.

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Why is it important?

This research is important because it identifies biomarkers that can predict the efficacy of adjuvant therapy and the risk of postoperative recurrence in patients with completely resected EGFR-mutated NSCLC. These findings can help guide treatment decisions, improve patient outcomes, and potentially reduce the need for unnecessary or ineffective treatments. Key Takeaways: 1. NOTCH1 co-mutation can serve as a poor prognostic factor for overall survival (OS) in the gefitinib group and may predict a poor response to adjuvant EGFR-TKI. 2. CREBBP co-mutation may be a biomarker for predicting a poor response to adjuvant platinum-based chemotherapy for completely resected EGFR-mutated NSCLC. 3. Further studies are needed to validate the utility of these biomarkers in patients receiving adjuvant osimertinib and to explore their potential in guiding treatment decisions.