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G. De Lima Lopes
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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P3.02b-057 - Network Meta-Analysis of First-Line and Maintenance Regimens in EGFR Mutated Advanced Non-Small-Cell Lung Cancer (NSCLC) (ID 4434)
14:30 - 14:30 | Author(s): G. De Lima Lopes
- Abstract
Background:
More evidence is needed to select the best first line treatment strategy for patients harboring EGFR mutations and its subtypes
Methods:
We performed a systematic search and included studies reporting OS and/or PFS efficacy estimates by EGFR mutation status or subtypes (Del19/L858R). Hazard ratios of competing treatments were pooled using a Bayesian hierarchical model incorporating both within and between study heterogeneities. Treatment benefits were evaluated using posterior hazard ratios with 95% credible intervals (CrI) and ranked by surface under the cumulative ranking curve (SUCRA) for OS benefit
Results:
4,177 records were screened and 20 trials were meta-analyzed. Statistically significant OS and PFS benefits were seen with (i) first-line intercalated chemotherapy+erlotinib in EGFR mutation positive, and (ii) first-line afatinib in Deletion 19. In L858R, no OS benefit was seen although treatments showed PFS benefitsFirst-line Maintenance All SUCRA OS PFS Chemotherapy+erlotinib Erlotinib[a] 91.5% 0.48 (0.26-0.88) 0.25 (0.15-0.43) Erlotinib+bevacizumab Erlotinib+bevacizumab 89.1% 0.40 (0.11-1.52) 0.18 (0.11-0.30) Afatinib Afatinib 65.0% 0.90 (0.74-1.10) 0.38 (0.29-0.49) Chemotherapy+bevacizumab Bevacizumab 54.8% 0.90 (0.38-2.14) 0.23 (0.12-0.45) Chemotherapy NoMaintenance 48.7% 1.00 1.00 Chemotherapy+erlotinib Erlotinib 48.5% 1.00 (0.66-1.50) 0.49 (0.18-1.31) Erlotinib Erlotinib 43.3% 1.03 (0.83-1.30) 0.32 (0.24-0.42) Gefitinib Gefitinib 43.0% 1.03 (0.86-1.23) 0.45 (0.37-0.56) Del19 Afatinib Afatinib 96.3% 0.59 (0.43-0.80) 0.24 (0.18-0.32) Gefitinib Gefitinib 69.3% 0.80 (0.58-1.11) 0.33 (0.26-0.43) Chemotherapy No maintenance 37.5% 1.00 1.00 Erlotinib Erlotinib 34.1% 1.03 (0.75-1.42) 0.20 (0.14-0.29) Chemotherapy Gefitinib 12.8% 1.89 (0.47-7.56) -
Conclusion:
Among all available strategies, first-line intercalated chemotherapy+erlotinib in EGFR mutation positive and afatinib in Del 19 are the only strategies showing both OS and PFS benefits
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P3.02b-081 - Comparative Outcome Assessment of EGFR TKIs for the Treatment of Advanced Non-Small-Cell Lung Cancer: A Network Meta-Analysis (ID 4904)
14:30 - 14:30 | Author(s): G. De Lima Lopes
- Abstract
Background:
Patients with advanced non small-cell lung cancer (NSCLC) whose tumors harbor activating mutations in the epidermal growth factor receptor (EGFR) gene, derive substantial clinical benefit from treatment with first and second-line EGFR tyrosine kinase inhibitors (EGFR-TKIs), including gefitinib, erlotinib and afatinib. However, their comparative effectiveness in this setting has not been evaluated, due to the paucity of randomized comparative clinical trials.
Methods:
We performed a comprehensive literature search in PUBMED, EMBASE, SCOPUS and ISI databases for randomized clinical trials evaluating either of the aforementioned EGFR-TKIs in first- and subsequent-lines treatment of EGFR-positive advanced NSCLC. All sensitizing mutations to EGFR-TKI inhibition were included in the current analysis. Patients with active brain metastases, with ECOG performance status of more than 2, as well as trials comparing the combination of EGFR-TKI with chemotherapy to chemotherapy alone were excluded. Comparative study outcomes included objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and rate of adverse events (AE). Cochrane guidelines were used for statistical analysis.
Results:
13 randomized trials incorporating 3,853 patients were eligible for the analysis. In the first-line setting, all EGFR TKIs showed improved outcomes with respect to ORR and PFS when compared to standard platinum-doublet chemotherapy. Comparative ORR rates for gefitinib, erlotinib and afatinib in first-line were 71.5%, 70.2% and 50.1% respectively. HRs for PFS were 0.40 (95% CI: 0.31- 0.50) for gefitinib, 0.25 (0.11-0.56) for erlotinib and 0.40 (0.28-0.57) for afatinib, all three with p<0.001. Respective HRs for OS were 0.89 (0.72-1.10) for Gefitinib, 0.91 (0.76-1.13) for erlotinib and 1.05 (0.88-1.25) for afatinib. No significant diferences were detected regarding common AEs (rash, diarrhea) among the three agents. Evidence data for gefitinib were less heterogeneous than those for erlotinib and afatinib.
Conclusion:
When compared indirectly, gefitinib exhibited the more consistent results from a statistical point of view and erlotinib had the more favorable profile regarding PFS prolongation. These data challenge the current landscape of first and second generation EGFR-TKIs in EGFR mutant advanced NSCLC and especially those of the recently reported LUX-LUNG 7 trial.
