RESUMO
The effectiveness of the tyrosine kinase inhibitor ALK (TKI) for non-small cell lung cancer has been confirmed. However, resistance to ALK-TKIs seems inevitable. Mutations in the ALK kinase domain have been reported as an important mechanism of acquired resistance to ALK therapy. However, patients with de novo ALK kinase domain mutations and ALK rearrangements who were not treated with ALK inhibitors have rarely been reported. Here, we report a case of primary drug resistance to first- and second-generation ALK inhibitors in a NSCLC patient with ALK-rearrangement. The next-generation sequencing test of the pathological biopsy showed that the de novo ALK kinase domain mutation F1174L-cis-S1189C may be the cause of primary drug resistance.
RESUMO
Aims: In this study, we determined whether different genotypes of drug-metabolizing enzymes are associated with the therapeutic effects of gefitinib in non-small cell lung cancer (NSCLC). Methods: A retrospective analysis of 112 patients with stage III or IV NSCLC was performed. The clinical characteristics of these patients, including progression-free survival (PFS), outcome of gefitinib treatment, and relationship between the genotypes of rs1065852/rs2242480 and prognosis, were analyzed. Results: The rs1065852 CT/TT genotype was associated with worse prognosis than the CC type (p = 0.0306), and the median PFS was lower than that with the CC type (287 days vs. 350 days). Compared with those with CC+CC genotypes, individuals carrying T alleles (CT/TT+CT/TT) at rs1065852/rs2242480 had a poorer prognosis, and the median PFS of CT/TT+CT/TT at rs1065852/rs2242480 was significantly lower than that of the CC+CC type (188 days vs. 444.5 days). Conclusions: Genotypes of the drug-metabolizing enzymes rs1065852 and rs2242480 have an impact on the prognosis of patients with NSCLC treated with gefitinib.
