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.
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.
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|
|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|
|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|
|Standard chemotherapy||No maintenance||37.5%||1.00||−|
|Chemotherapy + gefitinib||Gefitinib||12.8%||1.89 (0.47-7.55)||0.17|
|EGFR mutation L858R|
|Standard chemotherapy||No maintenance||69.2%||1.00||−|
|Chemotherapy + gefitinib||Gefitinib||35.3%||1.37 (0.38-4.96)||0.30|
|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|
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
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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