Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival
Por:
Lee, CK, Davies, L, Wu, YL, Mitsudomi, T, Inoue, A, Rosell, R, Zhou, C, Nakagawa, K, Thongprasert, S, Fukuoka, M, Lord, S, Marschner, I, Tu, YK, Gralla, RJ, Gebski, V, Mok, T and Yang, JCH
Publicada:
1 jun 2017
Resumen:
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 (Pinteraction = .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.
Filiaciones:
Lee, CK:
Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
St George Hosp, Canc Care Ctr, Sydney, NSW, Australia
Davies, L:
Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
Wu, YL:
Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China
Guangdong Acad Med Sci, Guangzhou, Guangdong, Peoples R China
Mitsudomi, T:
Kinki Univ, Fac Med, Dept Surg, Div Thorac Surg, Sayama, Osaka, Japan
Inoue, A:
Tohoku Univ, Sch Med, Dept Palliat Med, Sendai, Miyagi, Japan
:
Germans Trias & Pujol Hlth Sci Syst & Hosp, Catalan Inst Oncol, Barcelona, Spain
Zhou, C:
Tongji Univ, Shanghai Pulm Hosp, Sch Med, Dept Oncol, Shanghai, Peoples R China
Nakagawa, K:
Kinki Univ, Fac Med, Dept Med Oncol, Sayama, Osaka, Japan
Thongprasert, S:
Chiang Mai Univ, Fac Med, Chiang Mai, Thailand
Fukuoka, M:
Kinki Univ, Fac Med, Dept Med Oncol, Sayama, Osaka, Japan
Lord, S:
Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
Univ Norte Dame, Sch Med, Sydney, NSW, Australia
Marschner, I:
Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
Macquarie Univ, Dept Stat, Sydney, NSW, Australia
Tu, YK:
Natl Taiwan Univ, Coll Publ Hlth, Inst Epidemiol & Prevent Med, Taipei, Taiwan
Gralla, RJ:
Jacobi Med Ctr, Albert Einstein Coll Med, New York, NY USA
Gebski, V:
Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
Mok, T:
Chinese Univ Hong Kong, Hong Kong Canc Inst, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China
Bronze
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