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F Escande
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FP09 - Screening and Early Detection (ID 175)
- Event: WCLC 2020
- Type: Posters (Featured)
- Track: Screening and Early Detection
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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FP09.05 - Driver Oncogenic Alterations and Indoor Radon in NSCLC Patients From the IFCT Biomarker Cohort: Bioradon France Study (ID 1176)
00:00 - 00:00 | Author(s): F Escande
- Abstract
Introduction
Radon is a radioactive gas, considered as the leading cause of lung cancer in non-smokers. In a previous work, we studied the correlation between the estimation of radon concentration from the French Indoor Radon Map (Institut de Radioprotection et de Sûreté Nucléaire, IRSN) and the regional prevalence of driver alterations in a cohort of 116.424 NSCLC patients in France (Mezquita et al, WCLC 2018). The prevalence of driver oncogene alterations was significantly higher in high-radon areas but clinical data were not available. We aim to confirm this hypothesis in an annotated database of NSCLC patients with matched molecular data available for adjustment (Barlesi et al, Lancet 2016).
Methods
Retrospective assessment of patients with NSCLC tested for EGFR/BRAF/HER2/KRAS mutations (m) and ALK fusion from the 28 Platform led by the National Cancer Institute between Apr.2012 and Apr.2013, and included in the Biomarkers France dataset. We studied the association between the prevalence of driver oncogenic alterations (EGFR/ALK/BRAF/HER2/KRAS) and the radon mean concentration in the area where the patient was born according to the IRSN Map. Adjustment on age, gender and smoking was performed.
Results
Out of 17664 patients, we analyzed 3994 with birthplace available: 63% males, 82% smokers, with a median age of 64 years [18-94]. Lung cancer tumors were mostly adenocarcinoma (76%), followed by other histologies (18%) and squamous (6%). By molecular alterations: 468 tumors harbor EGFRm (12%), 129 ALK (3%), 89 BRAFm (2%), 32 HER2m (1%), 985 KRASm (25%); 2273 wildtype or harbor other non-driver alterations (control; 57%). Adenocarcinoma histology (83.7% vs. 80.2%, p=0.0034), and non-smoker habit (19.5% vs. 16.5%, p=0.0251) were more common in radon high-risk group (comparatively at the low risk group). The mean radon concentration by birthplace was 74.36 Bq/m3 ±53.28SD [range 16.6-622.3], and by molecular groups: EGFRm 72.49 Bq/m3 ± 47.98 SD [16.6-461.4], ALK 80.24 Bq/m3 ±55.22SD [19.3-384.7], BRAFm 73.22 Bq/m3 ±47.86SD [19.3-319.3], HER2m 72.74 Bq/m3 ±39.51SD Bq/m3 [27.8-231.3], KRASm 71.79 Bq/m3 ±53.32SD [16.6-576.8] and control group 75.67 Bq/m3 ± 54.5SD [16.6-622.3] (p=0.20). The prevalence of driver alterations was higher in high-radon areas (table 1; p=0.0472); but no significant difference was observed after adjustment on age, gender and smoking.
ConclusionLow radon
<50 Bq/m3High radon
≥50 Bq/m3P value
P value adjusted*
EGFR
Mutation
N (%)
155 (11.4%)
313 (13.2%)
0.1218
0.3024
Control (1)
N (%)
1199 (88.6)
2059 (86.8)
ALK
Fusion
N (%)
42 (3.4%)
87 (4.1%)
0.3272
0.4708
Control (1)
N (%)
1199 (96.6)
2059 (95.9)
BRAF
Mutation
N (%)
32 (2.6%)
57 (2.7%)
0.8708
0.9865
Control (1)
N (%)
1199 (97.4)
2059 (97.3)
HER2
Mutation
N (%)
7 (0.6%)
25 (1.2%)
0.0880
0.1781
Control (1)
N (%)
1199 (99.4)
2059 (98.8)
KRAS
Mutation
N (%)
375 (31.3%)
610 (29.6%)
0.3227
0.3478
Control (2)
N (%)
824 (68.7)
1449 (70.4)
DRIVER
Positive
N (%)
236 (16.4%)
482 (19%)
0.0472
0.2128
Control (1)
N (%)
1199 (83.6)
2059 (81)
(1) population no EGFRm, noBRAFm, no HER2m and no ALKr
(2) population no EGFRm, noBRAFm, no HER2m, no ALKr and no KRASm
*adjustment on age, gender and smoking
We observed a higher prevalence of driver oncogenic alterations in NSCLC patients born in high radon areas; but no significant difference was observed after adjustment on age, gender and smoker. This study warrants further research on radon gas and driver oncogenes.
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P84 - Targeted Therapy - Clinically Focused - ALK (ID 261)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P84.06 - Alectinib in ALK-Rearranged NSCLC Patients Following Crizotinib. Final Results and Biological Outcomes - Phase II ATALK Study (ID 3361)
00:00 - 00:00 | Author(s): F Escande
- Abstract
Introduction
Patients (pts) with advanced Anaplastic Lymphoma Kinase (ALK+) Non-Small Cell Lung Cancer (NSCLC) treated with crizotinib as first ALK inhibitor often develop acquired resistance during the 1st year of treatment. The ATALK study aimed at evaluating the efficacy and safety of alectinib, a 2nd generation ALK inhibitor, in selected pts with ALK-rearranged NSCLC, having progressed on prior treatment with crizotinib, without any supposed resistance mechanism to alectinib.
Methods
ATALK is an open-label, multicenter, single-arm, phase II study. Pts with ALK+ advanced or metastatic NSCLC progressing after crizotinib, whatever the line of treatment, received alectinib 600 mg twice daily until progressive disease (PD). Pts harbouring a mechanism suspected to confer resistance to alectinib (including selected ALK mutations, loss of ALK rearrangement, histological transformation) on a liquid or solid biopsy performed at inclusion were excluded. Pts were followed-up for 12 months.
The primary endpoint was the objective response rate (ORR) per investigator assessed from the Best Overall Response (BOR) using RECIST 1.1 within the 12 months following the first intake of alectinib.
Major secondary objectives were Progression-Free Survival (PFS), Overall Survival (OS), Disease Control Rate (DCR) and safety.
Results
Sixty four (64) pts were screened and 4 were excluded due to suspected resistance mechanisms to alectinib. A total of 44 pts were included (ITT/Safety population) and 39 pts had measurable disease at baseline (mITT population).
In the ITT population, 21 contributive fresh tumor tissue biopsies were obtained, all showed ALK rearrangement and absence of resistance mechanism to alectinib. Recruited pts were mostly men (57%), with a median age of 57 and an ECOG PS of 0-1 (89%)). Central nervous system (CNS) metastases were identified in 61% pts, of whom 16% had already been treated mainly with radiotherapy. All pts had ≥ 1 prior NSCLC therapy and 52% had received a 2nd therapy line; 11% had undergone ≥1 prior lung cancer surgery and 27 % ≥1 prior cancer radiotherapy.
In the mITT population, ORR was 51% (CI95%:34.8-67.6) and only 2 pts experienced a PD. The disease control rate was 94.9% (CI95%:82.7-99.4). In 11 pts with measurable CNS metastases at baseline, the CNS-ORR was 91% (CI95%:58.7-99.8).
In the ITT population, the median PFS was 14.4 months (9.2-NR). The OS rate at 12 months was 87.1% (71.6-94.4), median OS was not reached.
Efficacy outcomes regarding single nucleotide variants, ALK variants and ALK amplification are ongoing and will be presented later.
Grade ≥ 3 adverse events occurred in 34.1% pts, mainly respiratory disorders (13.6%) and cardiac disorders (6.8%). Death was reported in 11.4% pts, none was related to the treatment (pneumonia, stroke, general health deterioration, suffocation and ventricular dysfunction).
Conclusion
Alectinib efficacy and safety profile in this study align with known alectinib results in post-crizotinib setting. Identification of mechanisms of resistance emerging from exposure to previous ALK inhibitor was feasible and helped selecting subsequent treatment options.
