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. 2020 Jun;19(6):3859-3870.
doi: 10.3892/ol.2020.11502. Epub 2020 Apr 1.

Predictive value of tumor genetic alteration profiling for chemotherapy and EGFR-TKI treatment in advanced NSCLC

Wei Jiang  1 , Aiping Zeng  1 , Ruiling Ning  1 , Wenhua Zhao  1 , Cuiyun Su  1 , Huilin Wang  1 , Shaozhang Zhou  1 , Qitao Yu  1
Affiliations

Predictive value of tumor genetic alteration profiling for chemotherapy and EGFR-TKI treatment in advanced NSCLC

Wei Jiang et al. Oncol Lett. 2020 Jun.

Abstract

Previous studies have suggested that a variety of tumor driver genetic alterations affected the treatment efficacy of chemotherapy and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). The present study aimed to investigate the association between the tumor genetic alteration landscape and the treatment outcome of first-line chemotherapy and EGFR-TKIs in advanced NSCLC. A total of 94 patients with advanced NSCLC were recruited. All patients received first-line chemotherapy and/or EGFR-TKIs (either first- or second-generation EGFR-TKI, or third-generation EGFR-TKI) alone or sequentially. Prior to chemotherapy and/or EGFR-TKI treatment, plasma, effusion and/or tumor tissues from the included patients were subjected to next-generation sequencing, targeting 59 genes. The results indicated that the positive genetic alteration status prior to first-line chemotherapy was associated with prolonged progression-free survival (PFS) time compared with the negative status [9.1 vs. 4.0 months; hazard ratio (HR)=6.68; 95% CI, 2.25-19.82; P=0.001). Furthermore, patients with EGFR activating mutation harboring concomitant alterations exhibited a shorter PFS (11.1 vs. 7.4 months; HR=2.14; 95% CI, 1.03-4.44; P=0.04) and overall survival (OS) time [not reached (NR) vs. 32.8 months; HR=4.30; 95% CI, 1.41-13.16; P=0.01] than those without concomitant alterations, with first- and second-generation EGFR-TKI treatment. Similarly, patients with T79M mutation harboring concomitant alterations exhibited a shorter PFS (15.6 vs. 3.6 months; HR=9.48; 95% CI, 2.29-39.28; P=0.002) and OS time (NR vs. 32.8 months; HR=4.85; 95% CI, 1.16-20.29; P=0.03) with osimertinib treatment. Taken together, the results demonstrated that positive genetic alteration status predicted greater efficacy of first-line chemotherapy, while concomitant genetic alterations were associated with poor treatment outcome for first- or second-generation EGFR-TKI and third-generation EGFR-TKI treatment.

Keywords: EGFR-TKI; NGS; NSCLC; chemotherapy; tumor genetic alteration profiling.

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Figures

Figure 1.
Figure 1.
Genetic alterations prior to first-line chemotherapy based on next-generation sequencing, targeting 59 genes from 64 patients with advanced non-small cell lung cancer. PR, partial response; SD, stable disease; PD, progressive disease; VAF, variant allele frequency; EGFR, epidermal growth factor receptor.
Figure 2.
Figure 2.
Kaplan-Meier survival analyses of first-line chemotherapy among patients with advanced non-small cell lung cancer. (A) Kaplan-Meier estimates of progression-free survival (9.1 months vs. 4.0 months) between patients with and without genetic alterations; (B) Kaplan-Meier estimates of overall survival (47.0 months vs. 47.0 months) between patients with and without genetic alterations. HR, hazard ratio.
Figure 3.
Figure 3.
Genetic alterations prior to first- or second-generation EGFR-tyrosine kinase inhibitors treatment based on next-generation sequencing targeting 59 genes from 41 patients with advanced non-small cell lung cancer harboring EGFR mutation. EGFR, epidermal growth factor receptor; PR, partial response; SD, stable disease; PD, progressive disease; VAF, variant allele frequency.
Figure 4.
Figure 4.
Kaplan-Meier survival analyses among advanced EGFR-mutant non-small cell lung cancer. (A) Kaplan-Meier estimates of progression-free survival (11.1 months vs. 7.4 months) of first- or second-generation EGFR-tyrosine kinase inhibitors treatment between patients with and without genetic alterations; (B) Kaplan-Meier estimates of overall survival (NR vs. 32.8 months) of first- or second-generation EGFR-tyrosine kinase inhibitors treatment between patients with and without genetic alterations . NR, not reached; EGFR, epidermal growth factor receptor; HR, hazard ratio.
Figure 5.
Figure 5.
Genetic alterations prior to treatment with osimertinib based on next-generation sequencing, targeting 59 genes from 21 patients with T790M-positive cases resistant to first- or second-generation EGFR-tyrosine kinase inhibitors. EGFR, epidermal growth factor receptor; PR, partial response; SD, stable disease; PD, progressive disease; VAF, variant allele frequency.
Figure 6.
Figure 6.
Kaplan-Meier survival analyses among T790M-positive NSCLC. (A) Kaplan-Meier estimates of progression-free survival (15.6 months vs. 3.6 months) of osimertinib treatment between patients with or without concomitant alterations beyond EGFR; (B) Kaplan-Meier estimates of overall survival (NR vs. 32.8 months) of osimertinib treatment between patients with or without concomitant alterations beyond EGFR. NR, not reached; EGFR, epidermal growth factor receptor; HR, hazard ratio.
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