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ORAL 17 - EGFR Mutant Lung Cancer (ID 116)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 1
- Moderators:P. Meldgaard, E. Felip
- Coordinates: 9/08/2015, 10:45 - 12:15, Four Seasons Ballroom F3+F4
ORAL17.05 - Clinical Outcomes in Patients with Non-Small-Cell Lung Cancer (NSCLC) Harboring Rare Epidermal Growth Factor Receptor (EGFR) Mutations (ID 534)
10:45 - 12:15 | Author(s): C. Baldotto
The most described EGFR mutations are deletions in exon-19 and L858R in exon-21. They constitute approximately 50-90% of total EGFR mutations. Their clinical characteristics and sensitivity to EGFR tyrosine kinase inhibitors (EGFR-TKI) are well-known, given that they are described as classic/sensitizing mutations. Recently, despite the lower frequency G719X in exon-18, T790M and insertions in exon-20, and L861Q in exon-21 were described as uncommon EGFR mutations with known clinical significance having distinct features and EGFR-TKI sensitivity. Meanwhile, several other mutations have been reported and characterized as novel mutations. However, the characteristics and clinical benefit of EGFR-TKI in patients with these rare mutations remains unclear. This study aims to describe the epidemiology and the clinical outcomes of patients with rare EGFR mutations.
We retrospectively analyzed 287 patients with advanced NSCLC tested for EGFR mutations at the Brazilian National Cancer Institute from May-2011 to May-2014. Del 19 and L858R were described as classic EGFR mutations (CM). All other EGFR mutations, excluding uncommon mutations with known clinical significance (G719X, T790M, insertions in exon-20, and L861Q), were considered rare EGFR mutations (RM). All samples were formalin-fixed paraffin embedded (FFPE). The best response was considered as the best outcome the assistant physician registered in the medical chart. Time for Treatment Failure (TTF) was considered from the beginning of the treatment until suspension by the medical staff. Overall Survival (OS) was measured from diagnosis to death.
Of the 287 tested patients, 40 (14%) harbored CM, and 32 (11%) had RM. Only 7 patients harbored uncommon mutations with known clinical significance (1 with G719X and 6 with insertions in exon-20). Of the RM, 18 (56%) were women, 22 (69%) were ever-smokers and only 10 (31%) were never-smokers. RM were associated with smoking as compared to CM (p=0.04). OS was increased in the CM patients (26.4 v 13.4 v 13.7 months,p<0.001; for CM, RM and wild-type, respectively). Sixty patients received EGFR-TKI treatment with 17 harboring RM. Of these 17 RM treated patients, 5 received Erlotinib as first-line, 8 as second/third-line, and 4 as maintenance. When EGFR-TKI was started most patients had PS≤2 (89%). The best response documented was stable disease in 4 (24%) cases. All other 13 (76%) cases had progressive disease. Only three patients received Erlotinib for more than 6 months. Median-TTF was 3.4 months. Median-OS was 17.2 months. In seven cases the mutations have never been described before. In the Erlotinib-treated cohort, RM were associated with worse outcomes (TTF: 13.9 v 3.4 v 3.9 months,p<0.001; OS: 62.9 v 17.2 v 25months,p=0.002; for CM, RM and wild-type, respectively).
Clinical characteristics of rare EGFR mutant patients differ from classic EGFR mutant. Rare EGFR mutations also conferred little clinical benefit and short TTF with EGFR-TKI treatment. The TTF and OS in rare EGFR mutations were similar to EGFR wild-type patients. Thereby, in this subset of patients the indiscriminate use of EGFR-TKI should be abandoned.
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P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
P2.04-032 - Epidemiology and Clinical Outcomes of Epidermal Growth Factor Receptor (EGFR) Mutant Patients at the Brazilian National Cancer Institute (INCA) (ID 2794)
09:30 - 17:00 | Author(s): C. Baldotto
It is largely recognized the relationship between ethnicity and frequency of EGFR mutation. In Eastern Asia EGFR mutation prevalence in unselected lung adenocarcinoma reaches 52% as reported by large molecular studies. In withe populations, such as in European and North-American data, the EGFR mutation frequency decreases to 13-24%. Latin-America is a large and heterogeneous region with an elevated frequency of non-small-cell lung cancer (NSCLC) tumors. However, with the hurdles to access a high quality molecular test and targeted drugs, data regarding EGFR epidemiology in this region are lacking. For instance, in Brazil is estimated that less than 15% of advanced non-squamous cell lung cancer are tested. In this study, we describe the epidemiology and clinical outcomes of EGFR-mutant patients with advanced NSCLC after the implementation of EGFR reflex testing at a Brazilian public hospital.
From May-2011 to Dec-2014 we retrospectively collected data from EGFR reflex test at INCA. The test was recommended for all advanced non-squamous NSCLC patients treated at the institution. EGFR exons 18, 19, 20 and 21 were examined using either Cobas® platform or Sanger sequencing.
From May 2011 to Dec 2014, 288 samples were screened for EGFR mutations and 40 (13.9%) harbored common EGFR mutations (del19-L858R). Of all tested patients, 21% had >70 years-old, 56% were women and 26% were never-smokers. Most patients had adenocarcinoma (95%). Results were obtained from cytological specimen in 65 cases (23%). Sanger sequencing was performed in the majority of patients (73%). EGFR mutation frequency was significantly higher in females than in males (19%[13.4–25.4] vs 8%[4.4–13.9]), and in never-smokers (29%[20.2–40.4] vs 8%[5.1–12.6] in ever-smokers)[Table 1]. The median Overall Survival (OS) of the entire cohort was 15.1 months. EGFR mutation was associated with better OS, as compared with EGFR-WT (26.4 vs 13.7 months [HR-0.37;p<0.001], respectively). Other prognostic factors identified were age>70y (p=0.01) and stage IV (p=0.008). In the 40 EGFR-mutant patients, 32 received EGFR-TKI. The exposure to EGFR-TKI was associated with better survival as compared with no TKI treatment (62.9 vs 9.8 months [HR-0.25;p<0.01], respectively).Figure 1
Our results have demonstrated that the epidemiology and clinical outcomes of EGFR-mutant patients in a Brazilian cohort are in line with previous western studies. Further data with a higher number of patients and a wider extension are needed to confirm this results and point out possible intraregional differences.