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L. Bei
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MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
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MA 07.03 - Incidence, Predictors and Prognostic Significance of Thromboembolic Events in Patients with Advanced Alk-Rearranged NSCLCs (ID 9532)
15:45 - 17:30 | Author(s): L. Bei
- Abstract
- Presentation
Background:
The incidence of venous thromboembolic events all along the course of the disease in advanced-stage lung adenocarcinomas is approximately 15 %. It is plausible that the different molecular subtypes might influence on the risk of thrombosis. Based on our clinical observation, and supported by limited data from isolated small series, patients bearing ALK rearranged tumors could be at a particularly high-risk of thromboembolic disease.
Method:
We included consecutive patients diagnosed with advanced-stage ALK fusion positive non-small cell lung cancers (NSCLC) between January 2012 and December 2016. Clinical data were contributed by 29 Medical Centers from Spain and one large Academic Cancer Center from Portugal. Investigators at each institution retrospectively reviewed patients’ medical records. A thromboembolic event was defined as any venous or arterial thromboembolism, or both, at any site, documented by appropriate imaging studies, that occurred at the time or after advanced-stage cancer diagnosis.
Result:
A total of 241 ALK-rearranged NSCLCs were included in our study. Half of the patients were never smokers (52 %), and most had stage IV pulmonary adenocarcinomas (n=204, 85%). Baseline brain and liver metastasis were detected in 22 % and 25 % of the patients respectively. Seventy-three patients (30 %) developed thromboembolic disease. In 54 patients (74 %) thromboembolic complications occurred within the first 6 months from diagnosis. In the multivariate competing-risk regression analysis, the presence of baseline liver metastases (HR of 1.85, CI 95 % 1.09-3.15; p = 0.021) and baseline leukocyte counts > 11.0000 cells/mm3 (HR of 2.34, CI 95 % 1.43-3.82; p = 0.001) were independent predictors of thromboembolic disease. Remarkably, 50 % of the patients with either liver metastases or leukocytosis at diagnosis developed thromboembolic disease. Patients experiencing thromboembolic events had shorter median overall survival (OS) (20 months) than patients without thrombosis (36 months) (p = 0.035). In the multivariate Cox Model, thromboembolic disease remained associated with worse OS (HR of 1.70, CI 95 % 1.10-2.62; p = 0.016) when considered as a time-varying covariate. The presence of baseline thromboembolic disease (n = 24) was associated with a numerical non-significant increased risk of death (HR 1.67, CI 95 % 0.96-2.91; p = 0.068).
Conclusion:
Venous and/or arterial thromboembolic complications occur in a high proportion of patients with advanced-stage ALK fusion positive NSCLCs, particularly in the presence of baseline liver metastasis or leukocytosis. The development of thromboembolic disease is associated with a lower OS in these patients.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-049 - T790M Mutation Detection, Clinical Characteristics and Impact in NSCLC Patients Treated with EGFR Tyrosine Kinase Inhibitors (ID 9594)
09:30 - 16:00 | Author(s): L. Bei
- Abstract
Background:
All EGFR mutated lung cancers will eventually develop acquired resistance to first-line EGFR tyrosine kinase inhibitors (TKi). The most common cause is the EGFR T790M point mutation. Recent studies demonstrated the utility of liquid biopsies (LB) as initial detection strategy. The mutation may be indicative of a more indolent disease and plasma positivity seems to be related to more extensive disease.
Method:
Retrospective evaluation of T790M status and clinical characteristics of patients with advanced or recurrent non-small cell lung cancer (NSCLC) who progressed under EGFR-TKi was performed at our institution. The T790M mutation was assessed in circulating cell-free DNA (cfDNA) in plasma as initial strategy; if negative, a tumor biopsy (TB) was obtained. Samples were analyzed using Cobas® EGFR Mutation Test v2. The purposes of this study were: to explore the feasibility of T790M mutation detection in our practice; to evaluate objective response rate (ORR) and progression-free survival (PFS) on first-line TKi therapy according to T790M status and clinical characteristics.
Result:
We identified 29 patients. Regarding the pre-treatment activating EGFR mutations, 59% (n=17) harbored an exon 19 deletion, 38% (n=11) the L858R mutation and one case had both mutations (two primaries). All patients were treated with EGFR-TKi, 90% (n=26) in the first-line treatment setting. The T790M mutation was positive in 18 patients (12 plasma+ and 6 plasma-/tissue+). The remaining 11 negative results, 7 were assessed only by plasma and the other 4 were confirmed on TB. The resistance mutation was more frequent in patients with EGFR exon 19 deletions (71%, 12/17). In patients with a positive T790M result, those with extra-thoracic disease had detectable T790M mutation in plasma in the majority of cases (86%, 12/14), while all patients with exclusive intra-thoracic disease (n=4) had negative result in plasma. Patients who developed a T790M mutation had a longer PFS under first-line TKi, but not statistically significant (14 months in T790M+ [CI 95% 7.8-20.2] vs. 9 months [CI 95% 6.8-11.2] in T790M-, p=0.201) with similar ORR (55.6% in T790M+ vs. 45.5% in T790M-, p=0.597).
Conclusion:
The evaluation of EGFR T790M mutation is feasible in LB (cfDNA) in patients progressing under EGFR-TKi, but TB is recommended in the negative cases. The likelihood of detection of T790M in plasma is greater in patients with extra-thoracic disease, probably related with higher disease burden. Tumors which develop T790M tend to have a more indolent course, but the conclusion is limited due to the small sample size.
