Virtual Library
Start Your Search
Cecile Lepéchoux
Author of
-
+
OA09 - Prevention and Cessation (ID 909)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Prevention and Tobacco Control
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 15:15 - 16:45, Room 205 BD
-
+
OA09.06 - Molecular Alterations and Estimated Indoor Radon in NSCLC Patients from the French National Cancer Institute Registry: Radon France Study (ID 14168)
16:10 - 16:20 | Author(s): Cecile Lepéchoux
- Abstract
- Presentation
Background
Radon is a radioactive gas, considered the leading cause of lung cancer in non-smokers. We assessed the correlation between the radon exposure areas in France and the molecular alterations nationally registered in non-small cell lung cancer (NSCLC) patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
We retrospectively collected all NSCLC tested for EGFR, BRAF, HER2 and KRAS mutations (m) and ALK and ROS1 rearrangements (r) on the 28 French Plateform led by INCa (French National Cancer Institute). The prevalence of molecular alterations by region was correlated to the indoor radon risk area based on the official French (Institut de Radioprotection et de Sûreté Nucléaire, INSN, France). Paris and its region Ile-de-France were not included in this analysis due to its high rate of patients that are native from other regions.
4c3880bb027f159e801041b1021e88e8 Result
116.424 NSCLC were included. Overall, KRAS was positive in 27,7% (27.314/98.522), EGFR in 11,27% (13.125/116.424), ALK in 3,2% (2.928/91.291), BRAF in 2,3% (2.419/105.919), ROS1 in 1,12% (373/33.222) and HER2 in 0,8% (816/97.749) of all cases.
We stratified the French regions in 3 areas based on their exposure to radon: high (Auvergne-Rhône-Alpes, Bretagne, Normandie, Pays de la Loire), intermediate (Bourgogne-Franche-Comté, Nouvelle Aquitaine, Occitanie, Provence-Alpes-Cote-d'Azur) and low explosure (Centre Val-de-Loire, Grand Est, Hauts de France). The prevalence of driver alterations (EGFR, BRAF, HER2 and ROS1 were significantly higher in high exposure area. The prevalence of KRAS mutations was significantly higher in low exposure area.
8eea62084ca7e541d918e823422bd82e ConclusionLow risk
Intermediate
High
P
EGFR mutation
1962 (10%)
4338 (11%)
4176 (11.4%)
<0.0001
ALK rearrangement
577 (3.3%)
1019 (3%)
896 (3%)
0.35
BRAF mutation
327 (1.8%)
830 (2.4%)
692 (2.4%)
0.0001
HER2 mutation
109 (0.6%)
266 (0.9%)
252 (0.8%)
0.01
ROS1 rearrangement
61 (0.9%)
133 (0.9%)
126 (1.3%)
0.005
KRAS mutation
4717 (29.8%)
9215 (28.2%)
7895 (27%)
<0.0001
Molecular drivers*
3037 (3.9%)
6587 (4.4%)
6142 (4.4%)
<0.0001
* EGFR, BRAF & HER2 mutations, ALK & ROS1 rearrangements; KRAS mutation excluded.
NSCLC molecular alterations that are linked to low tobacco consumption were higher in the French region with high radon exposure. Role of the radon in lung cancer carcinogenesis of specific molecular subtypes should be further explored.
6f8b794f3246b0c1e1780bb4d4d5dc53Information from this presentation has been removed upon request of the author.
-
+
P2.13 - Targeted Therapy (Not CME Accredited Session) (ID 962)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
-
+
P2.13-24 - Prospective Efficacy of Osimertinib in Circulating Tumour DNA (ctDNA) T790M-Mutant NSCLC Patients (ID 14031)
16:45 - 18:00 | Author(s): Cecile Lepéchoux
- Abstract
Background
Liquid biopsy circulating tumor DNA (ctDNA) analysis in advanced EGFR-mutant NSCLC patients is an approved tool for molecular profiling and disease surveillance when tissue is not available. Long-term efficacy of osimertinib in patients with the T790M resistance mutation positive detected only by ctDNA (without tissue information) has not been fully validated.
a9ded1e5ce5d75814730bb4caaf49419 Method
In a prospective study, EGFR-mutant advanced NSCLC patients with acquired resistance to EGFR TKI, in whom a repeat tissue biopsy was not feasible, were assessed for ctDNA T790M mutational status using InVisionSeqTM. T790M-positive NSCLC patients received osimertinib (80 mg daily; extended access program or approval) at RECIST progression. The objectives were to assess: proportion of patients with acquired ctDNA-T790M positive; overall survival (OS) of the overall EGFR-mutant population as well as OS comparison for T790M +ve/-ve. Also, for those T790M-positive NSCLC patients who received osimertinib in a real world data we assessed: response rate (RR) according to RECIST 1.1 by investigator and progression free survival (PFS), calculated from the date of osimertinib initiation until the date of progression or death (whichever came first), or the date of last follow-up are also reported.
4c3880bb027f159e801041b1021e88e8 Result
We recruited 82 patients (71% female, median age 64 years, 72% Del19 EGFR mutation, 71% never-smokers). The ctDNA T790M mutation was detected in 55% (N=45) of NSCLC patients. Median OS of EGFR-mutant population was 38.2 months (mo.). According to T790M status, median OS was 41.2 months and 30.4 mo. for T790M-positive and T790M-negative NSCLC patients, respectively. Both cohorts had already received a median of 3 previous treatment lines. In 40 T790M-positive NSCLC patients who receive osimertinib, RR was 55% (PR: 55%, SD 27.5% and PD: 12.5%) and median PFS of 8.5 mo. Median OS on osimertinib among 10 patients with brain and/or leptomeningeal metastases at baseline was of 13.4 months.
8eea62084ca7e541d918e823422bd82e Conclusion
In patients with acquired resistance to first- or second-generation EGFR TKIs, ctDNA T790M detection by InVisionSeq™ is equivalent to what has been reported in tissue biopsy. Osimertinib has clinical benefit in patients for which the T790M resistance mutation is detected only through a liquid biopsy procedure.
6f8b794f3246b0c1e1780bb4d4d5dc53
