Subsequent chemotherapy improves survival outcome in advanced non-small-cell lung cancer with acquired tyrosine kinase inhibitor resistance.
BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide promising effect against non-small-cell lung cancer (NSCLC), although most tumors acquire resistance. Our objective was to assess the survival outcome of patients with NSCLC with or without subsequent chemotherapy after acquired TKI resistance.


METHODS
A total of 114 patients with pathologically confirmed stage IIIB or IV NSCLC who had had disease control with TKIs were retrospectively reviewed. After acquired TKI resistance, patients received either best supportive care (BSC) only or BSC plus subsequent chemotherapy. Both groups were well balanced in regard to performance status, age, sex, histology subtype, and smoking status.


RESULTS
Sixty-seven patients (58.8%) received subsequent chemotherapy, and 47 patients (41.2%) received BSC only. The median overall survival (OS) and progression-free survival (PFS) from the time of TKI resistance in the subsequent-chemotherapy group (11.2 months and 3.5 months, respectively) were longer than those of the BSC group (3.8 months and 1.5 months, respectively; P < .01). Patients who subsequently received taxane-based chemotherapy exhibited higher a response rate and disease control rate (48.7% and 79.5%, respectively) than patients treated with a nontaxane regimen (21.4% and 53.5%, respectively; P < .05). Overall survival and PFS in patients after taxane-based subsequent chemotherapy (12.7 months and 5.1 months, respectively) were longer than those of patients given a nontaxane regimen (7 months and 1.8 months, respectively; P < .01).


CONCLUSIONS
This study suggests that acquired TKI resistance should be managed aggressively. The higher antitumor response and survival outcome with a taxane-based regimen in this retrospective study could encourage further prospective investigation to confirm the efficacy of taxane over nontaxane chemotherapy in patients with NSCLC whose disease progresses with EGFR TKI treatment.
Kuo
Chih-Hsi
CH
Department of Thoracic Medicine, Chang Gung Memorial Hospital, Chang Gung University, School of Medicine, Taipei, Taiwan.
Lin
Shu-Min
SM
Lee
Kang-Yun
KY
Chung
Fu-Tsai
FT
Hsieh
Meng-Heng
MH
Fang
Yueh-Fu
YF
Yu
Chih-Ten
CT
Kuo
Han-Pin
HP
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016208:Databases, Factual; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D043823:Taxoids