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Fabrice Barlesi
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MA04 - Novel Approaches with IO (ID 900)
- Event: WCLC 2018
- Type: Mini Oral Abstract Session
- Track: Immunooncology
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 107
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MA04.03 - Immunotherapy for Non-Small Cell Lung Cancers (NSCLC) with Oncogenic Driver Mutations: New Results from the Global IMMUNOTARGET Registry (ID 13187)
13:40 - 13:45 | Author(s): Fabrice Barlesi
- Abstract
- Presentation
Background
Prospective data on immunotherapy for NSCLC with oncogenic driver mutations are limited. We recently reported first results from the global IMMUNOTARGET registry (Mazières, ASCO 2018). Here, we present new data for PD-L1 and mutation subgroups.
a9ded1e5ce5d75814730bb4caaf49419 Method
In 2017, we started an international retrospective registry study ("IMMUNOTARGET") for patients with advanced NSCLC, known driver mutations (KRAS, EGFR, ALK, ROS1, BRAF, HER2, MET and RET) and PD-L1 immune checkpoint inhibitor therapy. The registry is approved by University of Toulouse and Swissethics, and funded by University of Toulouse and Cantonal Hospital of Lucerne. Anonymized real-world data submitted to the coordinating center include: patient and tumor characteristics, mutation test methods and results, systemic therapy lines, immune related adverse events, best response by RECIST, survival, and tumor PD-L1 expression (optional). Statistical calculations including best response, median PFS and OS are done at University of Toulouse.
4c3880bb027f159e801041b1021e88e8 Result
In April 2018, the registry included 551 pts from Europe, USA, Israel and Australia. Patients were 50% male/female, 28% current smokers, median age 60 years (range 28-83), 85% had PS0/1. Most (73%) tumors were stage IV at diagnosis, almost all (96%) were adenocarcinomas. Molecular classification by dominant driver mutation: KRAS=271 (49%), EGFR=125 (23%), BRAF=43 (8%), MET=36 (7%), HER2=29 (5%), ALK=23 (4%), RET=16 (3%), ROS1=7 (1%), 1 (0.2%) not classified (ALK+RET+MET). Most pts received nivolumab (466) or pembrolizumab (48) and were treated with immunotherapy in second or third line (67%). The median number of cycles was 5 (range 1-68). Fifty (11%) pts had grade 3-5 toxicity. Median OS from start of immunotherapy was 13.3 months, median PFS was 2.8 months. Best response was PR/CR in: KRAS=26%, BRAF=24%, ROS1=17%, MET=16%, EGFR=12%, HER2=7%, RET=6%, ALK=0%. Percentage of PD-L1 positive cells was available for 177 pts: 0%=71 (40%), 1-49%=46 (26%), 50-100%=60 (34%). Median % of positive cells was highest for ROS1 (90%), BRAF (50%), MET (30%) and RET (26%) mutant tumors. PD-L1 positivity was predictive for improved PFS in KRAS and EGFR mutant tumors. PD-L1 status was known in 18 tumors with ALK, ROS1 or RET rearrangements: 5 had 0%, 4 had 1-49% and 9 had 50%-100%. No tumor remissions were observed in this subgroup. The registry remains open, updated results will be presented at the conference.
8eea62084ca7e541d918e823422bd82e Conclusion
Although response rates were lower than in KRAS mutant NSCLC, individual tumors with other driver mutations responded to immunotherapy. PD-L1 expression may not accurately predict clinical benefit from immunotherapy in some molecular subgroups, better markers are needed.
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MS26 - From Textbook to Practice Around the World (ID 804)
- Event: WCLC 2018
- Type: Mini Symposium
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 10:30 - 12:00, Room 205 AC
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MS26.03 - Translation of Clinical Data to Real World - Europe (ID 11513)
11:00 - 11:15 | Presenting Author(s): Fabrice Barlesi
- Abstract
- Presentation
Abstract not provided
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OA02 - Novel Therapies in ROS1, HER2 and EGFR (ID 893)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 10:30 - 12:00, Room 105
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OA02.01 - Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic ROS1 Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) (ID 13903)
10:30 - 10:40 | Author(s): Fabrice Barlesi
- Abstract
- Presentation
Background
Entrectinib is a central nervous system (CNS) active, potent, and selective inhibitor of ROS1, TRKA/B/C and ALK. Entrectinib is more potent against ROS1 than crizotinib, the only agent currently approved for the treatment of ROS1-positive NSCLC. Interim data demonstrated that entrectinib was tolerable and achieved high objective response rates (ORR) in patients with ROS1-positive, ROS1 inhibitor-naive NSCLC, including patients with baseline CNS disease (Ahn MJ WCLC 2017).
a9ded1e5ce5d75814730bb4caaf49419 Method
Phase 1/2 studies of entrectinib (ALKA, STARTRK-1, STARTRK-2; EudraCT 2012-000148-88; NCT02097810; NCT02568267) enrolled patients with locally advanced or metastatic solid tumors. The safety-evaluable population included patients who received ≥1 dose of entrectinib. The integrated efficacy analysis included ROS1-positive NSCLC patients enrolled based on identification of ROS1 fusions via nucleic acid-based diagnostic platforms. Safety was assessed by monitoring adverse events (AEs), laboratory tests, and physical examination. Tumor assessments were performed at the end of cycle 1 and every 8 weeks thereafter. All scans were submitted for blinded independent central review (BICR) using RECISTv1.1. Primary endpoints were ORR and duration of response (DOR) by BICR. Key secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Additional endpoints evaluated in patients with baseline CNS disease were intracranial ORR (defined as complete or partial responses in patients with baseline CNS lesions per BICR using RECISTv1.1), intracranial DOR, and PFS. For intracranial assessments, the CNS subgroup was derived per BICR; for systemic analyses, the CNS subgroup was derived per investigator.
4c3880bb027f159e801041b1021e88e8 Result
There were 53 efficacy-evaluable patients with treatment-naïve, ROS1-positive NSCLC. BICR ORR was 77.4% (95% CI 63.8–87.7) with complete responses in three patients (5.7%); median BICR DOR was 24.6 months (95% CI 11.4–34.8). Per baseline CNS status (as determined by investigator), median BICR PFS was 26.3 months (95% CI 15.7–36.6) and 13.6 months (95% CI 4.5–NR) for patients without (n=30) and with CNS disease (n=23), respectively. Intracranial ORR was 55.0% (95% CI 31.5–76.9) and median intracranial DOR was 12.9 months (95% CI 5.6–not reached [NR]) in patients with baseline CNS disease per BICR (n=20). In the overall safety-evaluable population (n=355), most treatment-related AEs were grade 1–2. Few patients required dose reduction (27.3%) or discontinued treatment (3.9%) due to treatment-related AEs.
8eea62084ca7e541d918e823422bd82e Conclusion
Entrectinib was tolerable with a manageable safety profile, and showed clinically meaningful, deep and durable systemic responses in ROS1-positive NSCLC. Clinically meaningful intracranial activity was also demonstrated in patients with baseline CNS disease.
6f8b794f3246b0c1e1780bb4d4d5dc53
Study Sponsor: Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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OA05 - Clinical Trials in IO (ID 899)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 13:30 - 15:00, Room 106
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OA05.05 - Avelumab vs Docetaxel for Previously Treated Advanced NSCLC: Primary Analysis of the Phase 3 JAVELIN Lung 200 Trial (ID 12930)
14:15 - 14:25 | Presenting Author(s): Fabrice Barlesi
- Abstract
- Presentation
Background
Avelumab is a human anti–PD-L1 IgG1 monoclonal antibody that is an approved treatment for metastatic Merkel cell carcinoma (various regions) and platinum-treated advanced urothelial carcinoma (US). We report findings from a global, open-label, phase 3 trial of avelumab vs docetaxel in patients with advanced NSCLC after platinum failure (NCT02395172).
a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with stage IIIB/IV or recurrent NSCLC with disease progression after platinum doublet therapy were randomized 1:1 to avelumab 10 mg/kg Q2W or docetaxel 75 mg/m2 Q3W, stratified by PD-L1 status (PD-L1+/PD-L1−) and histology (squamous/nonsquamous). The primary endpoint was overall survival (OS) in the PD-L1+ population (expression on ≥1% of tumor cells, assessed using the PD-L1 IHC 73-10 assay).
4c3880bb027f159e801041b1021e88e8 Result
Between April 2015 and February 2017, 792 patients were randomized to receive avelumab or docetaxel, including 264 and 265 with PD-L1+ tumors, respectively; 0.8% vs 7.5% did not receive study treatment. Median follow-up in the avelumab and docetaxel arms was 18.9 and 17.8 months; 15.5% vs 1.5% remained on treatment at data cutoff (November 22, 2017). In the avelumab and docetaxel arms, 39.8% vs 47.5% received subsequent anticancer therapy after discontinuation, including checkpoint inhibitors in 5.7% vs 26.4%, respectively. In the PD-L1+ population, median OS in the avelumab and docetaxel arms was 11.4 vs 10.3 months (hazard ratio [HR], 0.90 [96% CI, 0.72-1.12]; P=0.1627, 1-sided). Pre-planned exploratory analyses based on higher PD-L1 cutoffs showed increased OS with avelumab vs docetaxel, including PD-L1-high (≥80% cutoff, 29% of patients; 17.1 vs 9.3 months; HR, 0.59 [95% CI, 0.42-0.83]; P=.0022, 2-sided) and PD-L1-medium/high (≥50% cutoff, 40% of patients; 13.6 vs 9.2 months; HR, 0.67 [95% CI, 0.51-0.89]; P=0.0052, 2-sided) subgroups. In the PD-L1+ population (≥1% cutoff), ORR was 18.9% vs 11.7% (odds ratio, 1.76 [95% CI, 1.08-2.86]; P=0.0105, 1-sided); median duration of response was not reached with avelumab (95% CI, 9.9-not estimable [NE]) vs 6.9 months with docetaxel (95% CI, 3.5-NE). Overall rates of treatment-related adverse events (AEs) were lower with avelumab than docetaxel, including all grades (63.9% vs 85.8%) and grade ≥3 (9.9% vs 49.3%). Immune-related AEs occurred in 16.5% of avelumab-treated patients (grade ≥3 in 2.8%).
8eea62084ca7e541d918e823422bd82e Conclusion
Avelumab showed increasing clinical activity in patients who had platinum-treated NSCLC with higher tumor PD-L1 expression; however, the trial did not meet its primary objective of improving OS vs docetaxel in PD-L1+ tumors (≥1% cutoff). OS findings may have been confounded by subsequent checkpoint inhibitor therapy in the docetaxel arm.
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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
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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): Fabrice Barlesi
- 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.
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OA12 - Novel Therapies in MET, RET and BRAF (ID 921)
- Event: WCLC 2018
- Type: Oral Abstract Session
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 15:15 - 16:45, Room 106
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OA12.05 - Vemurafenib in Patients Harboring V600 and Non V600 BRAF Mutations: Final Results of the NSCLC Cohort from the AcSé Trial. (ID 12936)
16:00 - 16:10 | Author(s): Fabrice Barlesi
- Abstract
- Presentation
Background
BRAF mutations are found in 2-3% of NSCLC. BRAF inhibitors reportedly have antitumor activity. The French National Cancer Institute (INCa) launched a program giving nationwide access to vemurafenib for cancer patients with BRAF-mutated tumors and supported molecular screening. We herein report the NSCLC cohort results.
a9ded1e5ce5d75814730bb4caaf49419 Method
BRAF mutational status was assessed on INCa molecular genetic centers by direct sequencing or NGS. Patients with mutated BRAF (V600E and others mutations) progressing after ≥1 standard treatment were proposed vemurafenib 960 mg BID. Objective Response Rate (ORR) was assessed using RECIST v1.1 every 8 weeks. A sequential Bayesian approach was planned to allow early stopping using an inefficacy bound for ORR of 10%. If no early stopping occurred, the treatment was considered worthy for further evaluation if there was a 90% probability that the estimated ORR is ≥30%, the efficacy bound.
4c3880bb027f159e801041b1021e88e8 Result
From 10/2014 to 10/2017, 118 NSCLC patients were enrolled: 101 with BRAF V600E and 17 with other potentially activating mutations (4 G466, 4 G469, 1 G596, 5 K601, and 3 N581). Median age was 68 years (range 34–85), 71% smokers, 48% females, 100% non-squamous histology, and 20% with ECOG PS 2. Most frequent grade ≥3 adverse events (AEs) were asthenia (9% of patients), epidermoid carcinoma (6%), dermatitis (5%), and increased GGT (5%). Three toxic deaths were reported: 1 nausea and vomiting leading to dehydration, 1 pneumonia, and 1 neutropenic sepsis.
Nine patients were still on treatment at the cut-off date, 106 had stopped vemurafenib (65 PD, 26 AEs, 3 deaths, 1 doctor’s decision, 11 patient’s decisions).
8eea62084ca7e541d918e823422bd82e Conclusion
Vemurafenib provided reasonable response rate and extended PFS in pretreated NSCLC patients with BRAF V600E mutations but was not effective in those with other BRAF mutations. These results emphasize the need of integrating BRAF V600E in routine biomarkers screening.
6f8b794f3246b0c1e1780bb4d4d5dc53Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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P1.01 - Advanced NSCLC (Not CME Accredited Session) (ID 933)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.01-04 - Treatment Patterns and Overall Survival Following Biomarker Testing in Real-World Advanced NSCLC Patients (ID 12743)
16:45 - 18:00 | Presenting Author(s): Fabrice Barlesi
- Abstract
Background
Foundation Medicine (FMI) comprehensive genomic profiling and other next-generation sequencing (NGS) tests are gaining importance in routine clinical management of non-small cell lung cancer (NSCLC). They assess multiple genetic alterations that drive sensitivity or resistance to treatment, enabling optimal therapeutic decisions. We evaluated the effect of biomarker testing on treatment patterns and overall survival (OS) in real-world advanced NSCLC (aNSCLC) patients receiving different test types, and in non-tested patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
The Flatiron Health (FH) Database comprises patient-level electronic health records from a large network of US cancer clinics. Patients had aNSCLC diagnoses between 01/2013 and 05/2017, ≥2 clinic visits in the FH network, first treatment starting ≤90 days after aNSCLC diagnosis, and biomarker tests before first treatment. Testing data were abstracted for five biomarkers (EGFR, ALK, KRAS, ROS1, and PD-L1). Patients were hierarchically categorized into three testing groups: FMI, other NGS, and single-biomarker non-NGS. Biomarker status and patterns in first treatment were described. Cox proportional hazards models were used to compare OS among testing groups and non-tested patients.
4c3880bb027f159e801041b1021e88e8 Result
As of 11/30/2017, 355 patients had ≥1 FMI test, 780 had ≥1 other NGS test, and 6,363 had ≥1 non-NGS test prior to first treatment; 5,148 patients were never tested. Table 1 summarizes biomarker status, treatment patterns, and results of multivariate survival models adjusted for baseline demographic and clinical differences among testing groups. Patients with FMI tests were more likely to receive NCCN-recommended targeted treatments. Better OS was observed for FMI, other NGS, and non-NGS compared with non-tested patients.
FMI
Other NGS
Non-NGS
Non-tested
(n = 355)
(n = 780)
(n = 6,363)
(n = 5,148)
n
%
n
%
n
%
n
%
Biomarker status1
EGFR mutation
51
14.4
121
15.5
853
13.4
-
-
ALK rearrangement
8
2.3
23
2.9
187
2.9
-
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ROS1 rearrangement
0
0
3
0.4
33
0.5
-
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KRAS mutation
94
26.5
189
24.2
415
6.5
-
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PD-L1-positive
21
5.9
112
14.4
234
3.7
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Patterns in first treatment
NCCN-recommended
targeted therapy2,377
21.7
129
16.5
1,037
16.3
112
2.2
Non NCCN-recommended targeted therapy2,4
2
0.6
3
0.4
11
0.2
40
0.8
NCCN-recommended ICI2,5
36
10.1
102
13.1
381
6.0
229
4.4
Non NCCN-recommended ICI2,6
2
0.6
0
0
8
0.1
3
0.1
Multivariate Cox proportional hazards model to compare OS, hazard ratio (95% CI)
All aNSCLC7
0.72*
(0.61, 0.85)
0.74*
(0.66, 0.83)
0.78*
(0.74, 0.83)
1.00
(ref)
aNSCLC, non-squamous
cell histology80.69*
(0.61, 0.79)
0.76*
(0.70, 0.80)
0.69*
(0.57, 0.83)
1.00
(ref)
All aNSCLC9
0.93
(0.77, 1.13)
1.05
(0.92, 1.21)
1.00
(ref)
-
-
aNSCLC, non-squamous
cell histology100.91
(0.74, 1.13)
1.01
(0.87, 1.17)
1.00
(ref)
-
-
aNSCLC, non-EGFR-mutated, non-ALK-rearranged, non-squamous cell histology11
0.9
(0.74, 1.10)
0.94
(0.82, 1.08)
1.00
(ref)
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ECOG, Eastern Cooperative Oncology Group; ICI, immune checkpoint inhibitor; NCCN, National Comprehensive Cancer Network.1 Denotes biomarker status overall prior to starting first treatment and represents overall status from all test-types. In case of multiple tests, the following hierarchy is used: positive>negative>pending/unsuccessful/indeterminate/unknown.
2 Based on the NSCLC NCCN Guidelines, Version 3. 2018; 02/21/2018.
3 NCCN-recommended targeted therapy implies treatment regimens containing at least one of the following: erlotinib, afatinib, gefitinib, osimertinib, crizotinib, ceritinib, alectinib, brigatinib, dabrafenib+trametinib, cabozantinib, vandetanib, ado-trastuzumab emtansine.
4 Non NCCN-recommended targeted therapy implies treatment regimens containing at least one of the following: necitumumab, cetuximab, panitumumab, vemurafenib, dabrafenib, trametinib, trastuzumab, pertuzumab+trastuzumab, venetoclax.
5 NCCN-recommended ICI implies treatment regimens containing at least one of the following: pembrolizumab, nivolumab, atezolizumab.
6 Non NCCN-recommended ICI implies treatment regimens containing at least one of the following: ipilimumab, avelumab.
7 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, histology, and year of advanced diagnosis.
8 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, and year of advanced diagnosis.
9 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, histology, year of advanced diagnosis, sample type used for the test, and biomarker status.10 Adjusted for age, sex, race, clinic type, payer type, smoking history, stage at initial diagnosis, ECOG performance status, year of advanced diagnosis, sample type used for test, and biomarker status.
11 Adjusted for age, sex, race, clinic type, smoking history, stage at initial diagnosis, ECOG performance status, and year of advanced diagnosis.
* Indicates a statistically significant estimate (p<0.05).
8eea62084ca7e541d918e823422bd82e Conclusion
Complexity of real-world aNSCLC biomarker testing and associated treatments creates challenges when comparing OS among testing groups. In the future, as more treatments targeting a wider array of genomic alterations become available and accessible, the utility of NGS-based assays to guide NCCN-recommended treatments with actionable targets and differences in OS may become more apparent.
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P1.01-66 - Randomized Phase II Evaluating EGFR-TKI Associated with Anti-Estrogen in Women with Non-Squamous Advanced Stage NSCLC: IFCT-1003 LADIE Trial. (ID 13740)
16:45 - 18:00 | Author(s): Fabrice Barlesi
- Abstract
Background
The incidence of lung cancer is increasing dramatically in women with recent findings as the preferential involvement of the EGFR pathway and the potential impact of hormonal factors in women. Preclinical data have shown that the combination of an EGFR-TKI with an anti-estrogen could overcome resistance to EGFR-TKI.
a9ded1e5ce5d75814730bb4caaf49419 Method
IFCT-1003 LADIE Trial was a 2x2 arms parallel open-label randomized phase II trial. PS 0-2 post-menopausal women with advanced stage lung adenocarcinoma were treated with gefitinib (G 250 mg/day) vs. G + fulvestrant 500 mg / month with a supplementary dose at day 15 (G+F) in the EGFR mutated group (EGFR+) in 1st or 2nd line setting or with erlotinib (E 150 mg/day) vs. E + fulvestrant (E+F) in the EGFR wild-type group (EGFR WT) in 2nd or 3rd line setting until progression or unacceptable toxicity. Primary objective was progression-free survival (PFS) at 3 and 9 months for EGFR WT and EGFR+ patients, respectively.
4c3880bb027f159e801041b1021e88e8 Result
From 02/2012 to 03/2017, 204 pts (G 104, G+F 100) and 175 (E 87, E+F 88) were enrolled in the EGFR+ and EGFR WT cohorts respectively. The median number of fulvestrant injections was 10 in the G+F group and 3 in the E+F group. The tolerance was correct (grade 3/4: 24.2% in the G+F group vs 21.3% in the G group, 16.0% in the E+F group vs 13.8% in the E group) and no treatment-related death. In the EGFR+ cohort, the primary endpoint was reached as 54 pts in the G+F group were non-progressive at 9 months. Nevertheless, addition of F to G was not associated with significant better PFS (9.9 vs 10.1 months) or OS (22.1 vs 29.9 months). In the EGFR WT cohort, the primary endpoint was not reached as 29 patients were non-progressive at 3 months. Here also, addition of F to E was not associated with better outcome (PFS 1.8 vs 2.0 and OS 10.0 vs 7.3 months). No PFS difference was observed in the subgroup of patients with positive staining for REα.
8eea62084ca7e541d918e823422bd82e Conclusion
Addition of fulvestrant to EGFR-TKI is feasible and is associated with good PFS in the EGFR mutated group. Nevertheless, the lack of benefit associated with the combination of fulvestrant to EGFR-TKI does not support its future development in a phase 3 trial in women with NSCLC.
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.03 - Biology (Not CME Accredited Session) (ID 969)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.03-27 - Somatic BRCA1/2 Mutations in Advanced NSCLC Patients: Description of a Sub-Population from the Ongoing Unicancer SAFIR02-Lung / IFCT-1301 Trial (ID 13332)
12:00 - 13:30 | Author(s): Fabrice Barlesi
- Abstract
Background
Molecular profiling is considered standard of care in advanced NSCLC. Identification of druggable molecular alterations may enhance the percentage of patients suitable for personalized treatment.
a9ded1e5ce5d75814730bb4caaf49419 Method
From 04/2014 to 03/2017, 602 newly diagnosed,advanced NSCLC patients (pts) were enrolled in SAFIR02-Lung trial (NCT02117167). Molecular profile provided information on copy number alterations and mutations on 71 oncogenes and tumor suppressor genes. The profile was performed for 420 pts (70%) on archival tissue or frozen tissue collected from a new biopsy performed before the 3rd cycle (tissue or liquid) of chemotherapy. The frequency of BRCA mutation (mut) was assessed and clinicopathologic data collected. A homologous recombinant deficiency (HRD) score was performed on the copy number variations (CNV) data and the germline status was based on blood analysis. The BRCAshare database was the reference for the variants classification.
4c3880bb027f159e801041b1021e88e8 Result
18 pts were identified with BRCA alterations. BRCA variants of unknown significance were detected in 11 pts (2.6%). Response to chemotherapy according to RECIST 1.1 by investigator was: 6 stable disease (SD), 1 partial response, and 4 progressive disease (PD). CNV profile was evaluable for HRD in 6 out of 11 pts, with 50% positive.
Seven pts (1.7%) were identified with deleterious BRCA-mut. 2 pts (0.5%) harboured germline BRCA2-mut (1 with breast cancer familiar history). Both pts had SD to chemotherapy. Somatic BRCA-mut was identified in 5 pts (1.2%, 2 BRCA1- and 3 BRCA2-mut). All were male, 100% adenocarcinoma, 75% smokers of 40 pack/year, 1 pt with familial cancer history, and 80% of pts had bone metastases. Response to chemotherapy was: 4 SD, and 1 PD. Three of 7 corresponding CNV profiles were evaluable for HRD score analysis with 100% positive.
8eea62084ca7e541d918e823422bd82e ConclusionN=420
BRCA alterations (N=18)
BRCA VUS
N=11
BRCA deleterious
N=7
Somatic
6
5
Germline
5
2
HRD positive- Somatic
Germline
3/6*
2
1
3/3*
3
0
VUS: variants of unknown significance
*Amongst patients with available samples for analysis
Pathogenic BRCA1/2 mutations occur in 1.7% of advanced NSCLC with 71% of somatic mutations suggesting its value for exploring new therapeutic strategies in this population
6f8b794f3246b0c1e1780bb4d4d5dc53
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P3.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 982)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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P3.16-02 - Phase III Study of Canakinumab (ACZ885) as Adjuvant Therapy in Patients with Surgically Resected NSCLC (ID 12069)
12:00 - 13:30 | Author(s): Fabrice Barlesi
- Abstract
Background
Preclinical and clinical data suggest that cytokines such as interleukin (IL)-1β can promote angiogenesis and tumor growth, and are essential to tumor invasiveness. Canakinumab (ACZ885) is a high-affinity human IgGκ anti-IL-1β monoclonal antibody approved for patients with various IL-1–driven auto-inflammatory diseases. In the Phase III Canakinumab Anti-Inflammatory Thrombosis Outcomes Study (CANTOS) in patients with atherosclerosis, canakinumab was associated with a significant reduction in the incidence of fatal and non-fatal lung cancer in patients with increased high-sensitivity C-reactive protein levels. ACZ885T2301 (NCT03447769) is evaluating the efficacy and safety of adjuvant canakinumab versus placebo in patients with surgically resected non-small cell lung cancer (NSCLC).
a9ded1e5ce5d75814730bb4caaf49419 Method
This Phase III, randomized, double-blind, placebo-controlled study is enrolling patients (≥18 years, Eastern Cooperative Oncology Group Performance Status ≤1) with completely resected (R0) American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) v.8 stages II−IIIA and IIIB (T >5 cm and N2) NSCLC, who have completed standard-of-care adjuvant treatments, including cisplatin-based chemotherapy and mediastinal radiation therapy (if applicable). Prior treatment with neoadjuvant chemotherapy or radiotherapy is not permitted. Approximately 1500 patients will be randomized 1:1 to receive canakinumab (200 mg every 3 weeks [Q3W], subcutaneous [s.c.]) or placebo (Q3W, s.c.) on Day 1 of 21-day cycles for 18 cycles or until disease recurrence, unacceptable toxicity, treatment discontinuation at the discretion of the investigator or patient, death, or loss to follow-up. Following baseline screening, imaging assessment will be performed every 12 weeks for the first year (treatment phase) following Cycle 1 Day 1, then every 26 weeks during Years 2 and 3, and annually during Years 4 and 5 (post-treatment surveillance phase). Randomization will be stratified by AJCC/UICC v.8 stage, tumor histology, and region.
The primary objective is to compare disease-free survival (DFS) in the canakinumab versus placebo arms, as determined by local investigator assessment. Secondary objectives include a comparison of the two treatment groups with respect to overall survival (key secondary objective), lung cancer-specific survival, safety, pharmacokinetics and immunogenicity of canakinumab, and patient-reported outcomes. Exploratory objectives include assessment of the relationship between pharmacokinetics, pharmacodynamics, safety, and efficacy, and evaluation of correlation between cytokines/soluble markers and efficacy endpoints. Enrollment is ongoing.
4c3880bb027f159e801041b1021e88e8 Result
Section not applicable
8eea62084ca7e541d918e823422bd82e Conclusion
Section not applicable
6f8b794f3246b0c1e1780bb4d4d5dc53
