TY - JOUR
T1 - Gefitinib or erlotinib vs chemotherapy for EGFR mutation-positive lung cancer
T2 - individual patient data meta-analysis of overall survival
AU - Lee, Chee Khoon
AU - Davies, Lucy
AU - Wu, Yi Long
AU - Mitsudomi, Tetsuya
AU - Inoue, Akira
AU - Rosell, Rafael
AU - Zhou, Caicun
AU - Nakagawa, Kazuhiko
AU - Thongprasert, Sumitra
AU - Fukuoka, Masahiro
AU - Lord, Sally
AU - Marschner, Ian
AU - Tu, Yu Kang
AU - Gralla, Richard J.
AU - Gebski, Val
AU - Mok, Tony
AU - Yang, James Chih Hsin
PY - 2017/6
Y1 - 2017/6
N2 - Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P = .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P = .59) subgroups (P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P < .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.
AB - Background: We performed an individual patient data meta-analysis to examine the impact of first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy on overall survival (OS) in advanced non-small cell lung cancer (NSCLC).Methods: Data from trials comparing EGFR-TKI against chemotherapy in exon 19 deletion (del19) or exon 21 L858R (L858R) EGFR mutations patients were used. We performed Cox regression to obtain hazard ratios (HRs) and 95% confidence intervals (CIs). Impact of postprogression therapies was examined in exploratory analyses. All statistical tests were two-sided.Results: Six eligible trials (gefitinib = 3, erlotinib = 3) included 1231 patients; 632 received EGFR-TKI and 599 received chemotherapy. At a median 35.0 months follow-up, there were 780 deaths and 1004 progressions. There was no difference in OS between EGFR-TKI and chemotherapy (HR = 1.01, 95% CI = 0.88 to 1.17, P = .84). There was also no difference in OS for Del19 (n = 682, HR = 0.96, 95% CI = 0.79 to 1.16, P = .68) and L858R (n = 540, HR = 1.06, 95% CI = 0.86 to 1.32, P = .59) subgroups (P interaction = .47), or according to smoking status, sex, performance status, age, ethnicity, or histology. However, EGFR-TKI statistically significantly prolonged progression-free survival (PFS) overall (HR = 0.37, 95% CI = 0.32 to 0.42, P < .001) and in all subgroups. Following progression, 73.8% from the chemotherapy arm received EGFR-TKI, and 65.9% from the EGFR-TKI arm received chemotherapy. Nine percent from the EGFR-TKI arm received no further treatment vs 0.6% from the chemotherapy arm. Following disease progression, patients randomly assigned to EGFR-TKI had shorter OS than those randomly assigned to chemotherapy (12.8 months, 95% CI = 11.4 to 14.3, vs 19.8 months, 95% CI = 17.6 to 21.7).Conclusions: Despite statistically significant PFS benefit, there is no relative OS advantage with frontline gefitinib or erlotinib vs chemotherapy in EGFR -mutated NSCLC. This finding is likely due to the high rate of crossover at progression.
KW - mutation
KW - chemotherapy regimen
KW - non-small-cell lung carcinoma
KW - disease progression
KW - exons
KW - receptor
KW - epidermal growth factor
KW - erlotinib
KW - lung cancer
KW - protein-tyrosine kinase inhibitor
KW - gefitinib
UR - http://www.scopus.com/inward/record.url?scp=85027265241&partnerID=8YFLogxK
U2 - 10.1093/jnci/djw279
DO - 10.1093/jnci/djw279
M3 - Review article
C2 - 28376144
AN - SCOPUS:85027265241
SN - 0027-8874
VL - 109
SP - 1
EP - 9
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 6
M1 - djw279
ER -