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G. Mountzios
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P1.07 - Poster Session with Presenters Present (ID 459)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: SCLC/Neuroendocrine Tumors
- Presentations: 1
- Moderators:
- Coordinates: 12/05/2016, 14:30 - 15:45, Hall B (Poster Area)
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P1.07-018 - Incidence of Brain Recurrence and Survival Outcomes in High-Grade Neuroendocrine Carcinomas of the Lung: Implications for Clinical Practice (ID 3879)
14:30 - 14:30 | Author(s): G. Mountzios
- Abstract
Background:
Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage.
Methods:
Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated.
Results:
Overall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively), (Figure 1). Histologic subtype (LCNEC vs SCLC) was an independent prognosticator in multivariate analysis. In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 moFigure 1
Conclusion:
Patients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.
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P3.02b - Poster Session with Presenters Present (ID 494)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)
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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. Mountzios
- 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.
