Overall survival (OS) by EGFR mutation status and subtypes (Deletion 19/L858R) for first-line therapies with maintenance regimens in advanced non-small-cell lung cancer (NSCLC): a Bayesian multiple treatment comparison (MTC) meta-analysis

Date

20 Dec 2015

Session

Poster presentation 2

Presenters

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

Author affiliations

¹ Health Services And Systems Research, Duke-NUS Graduate Medical School, 169857 - Singapore/SG
² Oncoclinicas Do Brasil Group, Oncoclinicas do Brasil Group, SÃƒÂ£o Paulo/BR
³ Centre For Quantitative Medicine, Office Of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore/SG
⁴ Health Services And Systems Research, Duke-NUS Graduate Medical School, Singapore/SG
⁵ H. Milton Stewart School Of Industrial And Systems Engineering, Georgia Institute of Technology, Atlanta/US

Abstract 673

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.

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