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J.Z. Tan
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P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P3.04-026 - Reflex Testing of EGFR and ALK in Non-Squamous Non-Small Cell Lung Cancer (ID 476)
09:30 - 09:30 | Author(s): J.Z. Tan
- Abstract
Background:
Reflex molecular testing has affirmed the paradigm shift in the classification of tumors by genetic profile, in addition to conventional histopathology. It plays a critical role in identifying actionable targets and prompt allocation of patients to the appropriate treatment. We sought to compare the clinical characteristics and treatment outcomes between patients with genetic alterations against wild-type (WT) tumors for both EGFR and ALK in non-squamous non-small cell lung cancer (NSCLC) to examine the impact of reflex testing which was recently implemented in the National Cancer Centre Singapore.
Methods:
We analyzed all NSCLC patients diagnosed between Jan 2010 and Mar 2014 from a prospective database maintained by the Lung Cancer Consortium Singapore. Patients underwent reflex Sanger-based EGFR analysis from 2010 and ALK-FISH analysis from 2012. These analyses were undertaken upon histological diagnosis, regardless of the AJCC stage at presentation. Clinical characteristics of the mutant and WT groups were compared using chi-squared and Mann Whitney U tests. Overall survival(OS) was estimated using Kaplan-Meier method. Survivals were compared using log-rank test, and prognostic factors were determined using multivariate cox regression.
Results:
The overall EGFR mutation rate in our cohort (n=1308) was 51.4%. The corresponding rates in adenocarcinoma and non-adenocarcinoma groups were 52.5% and 34.9% respectively. EGFR mutants were more prevalent among females, never-smokers, and less symptomatic. A higher proportion had better ECOG status, well to moderately differentiated histology, more sites of distant metastases especially in the lungs and bones, presented with Stage IV, , and received more lines of palliative treatment (all p<0.05). The median OS(months) for the mutant group was 24.8 versus 13.3 for the WT group (p<0.001). Prognostic factors included ethnicity, smoking status, stage, histology, number of symptoms, ECOG status, number of metastatic sites, treatment intention and EGFR tyrosine kinase inhibitor (TKI) treatment (all p<0.02). The overall ALK alteration rate (n=405) was 12.6%, 12.4% in adenocarcinoma and 15.2% in non-adenocarcinoma. Contrary to prior reports, there were no differences in gender, diagnosis age, and smoking status between fusion and WT groups. The percentage of ALK fusion among Malays was higher (26.3% vs 7.9%; p=0.031). While ALK fusion had more lines of palliative treatment than WT, there was no significant difference in OS between both groups. Prognostic factors include gender, ethnicity, ECOG status, treatment intent, and number of palliative treatment and metastatic sites (all p<0.02).
Conclusion:
This study demonstrated significant differences in clinical features, management and subsequent response to treatment between genetically altered and WT patients for both EGFR and ALK profiles, reiterating the importance of reflex testing in patient management. While significant survival benefit was demonstrated with EGFR TKI therapy in EGFR cohort, this was not demonstrated for the ALK cohort, which can be attributed to the relative lack of access to ALK TKI (93% treated with EGFR TKI compared to 46.6% treated with ALK TKI). Finally, the considerable rate of EGFR and ALK mutations in non-adenocarcinoma groups reflects the need to extend reflex testing to these patient groups, and not just in patients with adenocarcinoma or adenocarcinoma components.
