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E. Caballe-Perez
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P2.03b - Poster Session with Presenters Present (ID 465)
- Event: WCLC 2016
- Type: Poster Presenters Present
- Track: Advanced NSCLC
- Presentations: 2
- Moderators:
- Coordinates: 12/06/2016, 14:30 - 15:45, Hall B (Poster Area)
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P2.03b-003 - Mutation Profile & Histology According to ERS/ATC/IASCL Associated with IPFS to WBI in BM Patients with Recent Adenocarcinoma Lung Cancer (ID 5817)
14:30 - 14:30 | Author(s): E. Caballe-Perez
- Abstract
Background:
Brain-metastases (BM) are a common metastatic site in non-small-cell lung cancer (NSCLC). We studied the impact of genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR), intracranial-progression-free survival (IPFS) and overall-survival (OS) after whole-brain irradiation (WBI) in patients at recently diagnosis with NSCLC and BM.
Methods:
From 2009-2015, 231 NSCLC patients with BM were reviewed for eligibility. Among them, 121 patients with recently diagnosis of NSCLC, were treated with WBI and have available genotyping status.
Results:
EGFR, KRAS, ALK and WT patients were found in 38.0%, 6.6%, 5.8% and 49.6%, respectively. Overall, ORR and disease control rate (DCR) were 62.0% and 76.8%, respectively. ORR for EGFR, KRAS, ALK and WT patients were 82.6%, 25.0%, 71.4% and 50.0%, respectively (p=0.001). Female gender (OR 2.22 [95% CI: 1.01 – 4.89] P=0.047) and EGFR were associated to better response to WBI (OR 5.67 [95% CI 2.0-15.8], P = 0.001). A high architectural histological grade was independently associated with resistance to WBI. Median IPFS was 9.06 months [95% CI 6.5 -11.4]. IPFS for EGFR, K-RAS,ALK and WT patients were 11.9, 4.6,12.5 and 6.6 months, respectively (P <0.0001). EGFR mutation status (HR 0.54 [95%CI 0.3-0.9], P = 0.030) was the only factor associated with higher IPFS in the multivariate Cox-regression analysis. Median OS was 16.6 months [95% CI 11.6-22.6]. OS for EGFR, ALK, KRAS and WT patients were 26.8, 13.5, 4.9 and 13.6 months, respectively (P < 0.001). Intracranial OR was associated with a higher OS (HR 0.28 [95%CI 0.2-0.5], P < 0.001), while KRAS mutation positive status (HR 3.45 [95%CI 1.4-8.4], P = 0.006) was independently associated with worse OS. Figure 1
Conclusion:
EGFR mutation is an independent predictive factor for OR to WBI for BM in patients with NSCLC. KRAS mutation is an independent predictive factor for worse OS after BM.
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P2.03b-025 - Mutation Profile and Histology Subtype According to IASLC/ERS/ATC as Risk Factors for Brain Metastases in Lung Adenocarcinoma (ID 5850)
14:30 - 14:30 | Author(s): E. Caballe-Perez
- Abstract
Background:
Brain metastases (BM) are common among patients with adenocarcinoma, affecting treatment response, quality of life and overall survival(OS). We examine the impact of the main histological pattern and the genetic alterations in EGFR and ALK on the incidence of BM in patients with advanced non-small cell lung cancer (NSCLC).
Methods:
From January 2004 through December 2014 the medical records of 991 patients with NSCLC were reviewed for eligibility, among them 711 had adenocarcinoma histology. We describe the factors associated with the overall incidence of BM as well as the incidence of BM stratified on the histological grade pattern according to the ERS/ATC/IASLC classification (lepidic vs acinar+papilar vs micropapilar+solid).
Results:
Among 711 patients, 53.6% were female, 47.1% were less than 60 years-old at the time of diagnosis, exposure to tobacco, wood-smoke and asbestos were found in 52.0%, 40.5% and 13.8%, respectively. Seventy-six percent had a good performance status, and nearly sixty percent (59.8%) had oligometastatic disease. Most of the patients had a stage IV disease at the time of diagnosis (79.3%). Regarding histological grade classification, male patients were more likely to have a poorly differentiated adenocarcinoma in comparison with women (61.2% vs. 51.2%, p=0.027), as well as ever-smokers compared with non-smokers (61.4% vs. 49.9%). Likewise, patients harboring an ALK rearrangement were more likely to have a highly- or moderate differentiated adenocarcinoma (100% vs. 43.6%, p=0.008). A total of 122 patients (17.1 %) had a brain metastasis at diagnosis and 37.4% had baseline carcinoembryonic levels above 20 pg/ml.By Kaplan-Meier method 6.45% and 12.10% of patients developed BM at 12 and 24 months. The factors associated with a high incidence of BM were: female gender (40.9% vs. 34.4%; p=0.036), age < 60 years (44.4% vs. 32.1%, p=<0.001), EGFR activating mutation (53.9% vs. 39.3%; p=0.001), advanced metastatic disease (IIIB vs IV 42.8% vs. 20.3%; p=<0.0001), serological carcinoembryonic level >20pg/ml (47.2% vs. 32.8%; p=<0.0001) Finally, brain metastases were more likely to be found among patients with moderate and poorly-differentiated adenocarcinomas in comparison with highly differentiated adenocarcinomas (54.2, and 48.1% vs. 7.7%; p=0.050). In the multivariate analysis EGFR (HR:0.63;95%CI 0.44-0.92, p=0.017) and highly differentiated adenocarcinomas EGFR (HR:1.59;95%CI 1.03-2.44, p=0.034) were found to be independent factors for the development of BM.
Conclusion:
Adenocarcinoma histological-architectural-grade differentiation according to ERS/ATC/IASCL classification was found to be a predictive factor for development of BM like other previously described clinically characteristics (e.g. gender, age, EGFR activating mutations and carcinoembryonic-antigen).
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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-125 - Failure to Tyrosine Kinase Inhibitors and Patterns of Progression in Patients with Advanced Non-Small Cell Lung Cancer (ID 5089)
14:30 - 14:30 | Author(s): E. Caballe-Perez
- Abstract
Background:
Some studies have evaluated the impact of patterns of progression after treatment with tyrosine kinase inhibitors (TKI) in non-small cell lung cancer (NSCLC). We evaluated the patterns of progression and prognosis of NSCLC patients that received TKI.
Methods:
Using the criteria established by Yang to define models of progression to TKI we did a retrospective analysis. Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis.
Results:
Eighty-three NSCLC patients were included: 43 patients with dramatic-progression (51.8%), 26 with gradual-progression (31.3%), and 17 with local-progression (16.9%); demographic and clinical characteristics were similar in all subgroups. There was a significant difference in the median Progression-Free Survival (PFS) among the three groups, for the group with dramatic-progression it was 9.1 months, 16 months for gradual-progression and 11.9 for local-progression (P: 0.044). The overall survival (OS) was different among the three groups, for patients in gradual-progression 56 months, for patients in dramatic-progression 30 months and local-progression 36.4 months (figure A). Additionally 41.7% were treated with afatinib after progression to erlotinib and gefitinib. PFS in all patients was 8.08 months. Patients that present asymptomatic progression have a longer OS compared to those who present symptomatic progression (42 vs 31.9 months; p = 0.048). Figure 1
Conclusion:
There is a subgroup of patients with NSCLC and EGFR mutations with better prognosis and they can be identified according to the pattern of progression and presence of symptoms, as well as the duration of response during treatment. These could help decide which patients will benefit from continuing the anti-EGFR therapy beyond progression or to prescribe an aggressive approach when there is oligometastatic disease or local progression, especially in countries where access to third-generation TKIs is limited.
