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- Title
Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival.
- Authors
Chee Khoon Lee; Davies, Lucy; Yi-Long Wu; Tetsuya Mitsudomi; Akira Inoue; Rosell, Rafael; Caicun Zhou; Kazuhiko Nakagawa; Thongprasert, Sumitra; Masahiro Fukuoka; Lord, Sally; Marschner, Ian; Yu-Kang Tu; Gralla, Richard J.; Gebski, Val; Mok, Tony; Yang, James Chih-Hsin; Lee, Chee Khoon; Wu, Yi-Long; Mitsudomi, Tetsuya
- Abstract
<bold>Background: </bold>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).<bold>Methods: </bold>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.<bold>Results: </bold>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).<bold>Conclusions: </bold>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.
- Subjects
META-analysis; PROGNOSIS; EPIDERMAL growth factor receptors; PROTEIN-tyrosine kinase inhibitors; NON-small-cell lung carcinoma; CANCER treatment
- Publication
JNCI: Journal of the National Cancer Institute, 2017, Vol 109, Issue 6, p1
- ISSN
0027-8874
- Publication type
journal article
- DOI
10.1093/jnci/djw279