444P - Overall survival (OS) by EGFR mutation status and subtypes (Deletion 19/L858R) for first-line therapies with maintenance regimens in advanced non-s...

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Pui San Tan
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors P.S. Tan1, G. Lopes2, S. Aacharyya3, M. Bilger4, B. Haaland5
  • 1Health Services And Systems Research, Duke-NUS Graduate Medical School, 169857 - Singapore/SG
  • 2Oncoclinicas Do Brasil Group, Oncoclinicas do Brasil Group, São Paulo/BR
  • 3Centre For Quantitative Medicine, Office Of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore/SG
  • 4Health Services And Systems Research, Duke-NUS Graduate Medical School, Singapore/SG
  • 5H. Milton Stewart School Of Industrial And Systems Engineering, Georgia Institute of Technology, Atlanta/US

Abstract

Aim/Background

Survival benefits with first-line treatments followed by maintenance regimens in advanced NSCLC patients remain unclear. This MTC meta-analysis compared first-line treatments followed by maintenance regimens head-to-head by EGFR mutation status and subtypes.

Methods

PubMed and conference proceedings were searched for phase II/III randomized controlled trials comparing first-line treatments followed by maintenance regimens in advanced NSCLC patients. Individual study OS hazard ratios (HRs) by EGFR mutation status and subtypes were meta-analyzed using a Bayesian hierarchical model. Treatment efficacies were compared using (i) surface under the cumulative ranking curve (SUCRA), a summary estimate of treatment efficacy, (ii) posterior HRs with 95% credible intervals (CrI), and (iii) probability better than standard chemotherapy with no maintenance. Clinically meaningful OS benefit was defined by (i) ≥20% reduction in hazards of death and (ii) ≥90% probability to perform better than standard chemotherapy with no maintenance.

Results

4,156 records were screened and 18 trials with relevant information were included. Results are shown in Table. Clinically meaningful OS benefits were demonstrated with first-line (i) intercalated chemotherapy + erlotinib or erlotinib + bevacizumab in EGFR mutation positive, (ii) afatinib or gefitinib in Deletion 19, and (iii) chemotherapy + bevacizumab in EGFR wild-type, each with corresponding maintenance regimens as in Table. No treatments compared within L858R suggested clinically meaningful OS benefit.

Overall survival by EGFR mutation status and subtypes for first-line therapies with maintenance regimens in advanced NSCLC

First-line Maintenance SUCRA Overall survival, HR (95% CrI) Probability better than standard chemotherapy with no maintenance
EGFR mutation positive
Intercalated chemotherapy + erlotinib Erlotinib 91.1% 0.48 (0.26-0.88) 0.99
Erlotinib + bevacizumab Erlotinib + bevacizumab 88.6% 0.40 (0.11-1.52) 0.91
Afatinib Afatinib 61.2% 0.91 (0.72-1.14) 0.81
Chemotherapy + bevacizumab Bevacizumab 52.2% 0.90 (0.38-2.14) 0.60
Standard chemotherapy No maintenance 45.9% 1.00
Chemotherapy + erlotinib Erlotinib 45.5% 1.00 (0.66-1.51) 0.50
Erlotinib Erlotinib 41.1% 1.03 (0.82-1.29) 0.40
Gefitinib Gefitinib 40.6% 1.03 (0.84-1.26) 0.38
Chemotherapy + cetuximab Cetuximab 24.7% 1.22 (0.76-1.96) 0.20
Chemotherapy + gefitinib Gefitinib 9.2% 1.66 (0.82-3.35) 0.08
EGFR mutation Deletion 19
Afatinib Afatinib 96.3% 0.59 (0.43-0.80) >0.99
Gefitinib Gefitinib 69.3% 0.80 (0.58-1.11) 0.91
Standard chemotherapy No maintenance 37.5% 1.00
Erlotinib Erlotinib 34.1% 1.03 (0.75-1.42) 0.42
Chemotherapy + gefitinib Gefitinib 12.8% 1.89 (0.47-7.55) 0.17
EGFR mutation L858R
Erlotinib Erlotinib 69.4% 0.98 (0.70-1.37) 0.54
Standard chemotherapy No maintenance 69.2% 1.00
Gefitinib Gefitinib 47.8% 1.11 (0.76-1.63) 0.29
Chemotherapy + gefitinib Gefitinib 35.3% 1.37 (0.38-4.96) 0.30
Afatinib Afatinib 28.4% 1.25 (0.89-1.77) 0.10
EGFR wild-type
Chemotherapy + bevacizumab Bevacizumab 95.2% 0.57 (0.35-0.94) 0.99
Intercalated chemotherapy + erlotinib Erlotinib 75.0% 0.77 (0.51-1.17) 0.89
Chemotherapy + gefitinib Gefitinib 60.3% 0.89 (0.63-1.25) 0.76
Chemotherapy + cetuximab Cetuximab 58.3% 0.91 (0.71-1.17) 0.80
Erlotinib + bevacizumab Erlotinib + bevacizumab 43.1% 1.00 (0.50-2.01) 0.50
Standard chemotherapy No maintenance 42.1% 1.00
Chemotherapy + erlotinib Erlotinib 40.9% 1.02 (0.67-1.54) 0.46
Gefitinib Gefitinib 22.6% 1.16 (0.85-1.59) 0.17
Erlotinib Erlotinib 12.5% 1.29 (0.91-1.82) 0.07

Conclusions

Particular first-line treatments with maintenance regimens show clinically meaningful survival benefits in patients selected by EGFR mutation status and subtype Deletion 19.

Clinical trial identification

Disclosure

G. Lopes: research funds and honoraria from Astra Zeneca, Roche, Boehringer Ingelheim, Eli Lilly. All other authors have declared no conflicts of interest.