Outcomes by <i>EGFR</i>, <i>KRAS</i>, and <i>ALK</i> Genotype After Combined Modality Therapy for Locally Advanced Non-Small-Cell Lung Cancer.
retrospective_cohort · Level III
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- Also identified by DOI 10.1200/PO.17.00219.
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Abstract
In 699 patients with locally advanced non-small-cell lung cancer (NSCLC) treated with radiation therapy as part of combined modality therapy, we compared outcomes among genotyped and ungenotyped patients and by tumor genotype status (<i>EGFR</i>, <i>KRAS</i>, and <i>ALK</i>). Genotyping was performed in 250 patients: <i>EGFR+</i> (19%), <i>KRAS+</i> (32%), <i>ALK</i>+ (9%), and wild type (WT<sup>-/-/-</sup>; 40%). Outcomes were analyzed using the Kaplan-Meier method and Cox regression. With a median follow-up of 48.2 months among genotyped patients, median overall survival (OS) was significantly longer for <i>EGFR+</i> and <i>ALK+</i> compared with <i>KRAS+</i> and WT<sup>-/-/-</sup> (55.8 months <i>v</i> not reached <i>v</i> 28.0 <i>v</i> 33.2 months; <i>P</i> = .02). There was no difference in progression-free survival (median, 15.3 <i>v</i> 13.7 <i>v</i> 13.0 <i>v</i> 14.5 months; <i>P</i> = .47) or in freedom from distant metastases by genotype (3-year estimates: 42% <i>v</i> 49% <i>v</i> 27% <i>v</i> 25%; <i>P</i> = .25). There was higher freedom from locoregional recurrence (LRR) for <i>EGFR+</i> tumors and lower freedom from LRR in <i>ALK</i>+ tumors, compared with <i>KRAS+</i> and WT<sup>-/-/-</sup> tumors (3-year: 77% <i>v</i> 38% <i>v</i> 49% <i>v</i> 46%). In multivariable analysis, <i>ALK+</i> remained associated with increased OS (HR, 0.32; 95% CI, 0.12 to 0.87; <i>P</i> = .03), and <i>EGFR+</i> was associated with decreased LRR (HR, 0.47; 95% CI, 0.24 to 0.92; <i>P</i> = .03). Analysis of post-recurrence survival demonstrated that <i>EGFR+</i>/<i>ALK+</i> patients treated with appropriate tyrosine kinase inhibitors had higher OS compared with other groups. In this series of locally advanced NSCLC treated with combined modality therapy, <i>EGFR+</i> and <i>ALK+</i> were associated with higher OS, whereas LRR was lower in <i>EGFR+</i> patients, and the risk of distant metastases was high in all subgroups. The outcomes and patterns of failure in genotypic subgroups of NSCLC from this study can inform the design of future trials integrating targeted therapies.