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Isabelle Monnet
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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): Isabelle Monnet
- 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: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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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): Isabelle Monnet
- 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.
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P1.04 - Immunooncology (Not CME Accredited Session) (ID 936)
- 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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P1.04-31 - Efficacy and Tolerance of Immune-Checkpoint Inhibitors in EGFR, ALK/ROS 1 Non-Small-Cell-Lung-Cancer (NSCLC): GFPC 03-2016 IMAD Study (ID 11166)
16:45 - 18:00 | Author(s): Isabelle Monnet
- Abstract
Background
Patients with molecular alterations are considered to be poor candidates for immune- checkpoint inhibitors (ICI) on the second-line phase III trials. Here, we analyze the efficacy of ICI in EGFR /ALK/ROS1 NSCLC patients in real world setting
a9ded1e5ce5d75814730bb4caaf49419 Method
This retrospective, multicentric study in EGFR, ALK and ROS1 NSCLC treated by ICI, analyzed clinical characteristics and outcomes (progression free survival (PFS), duration of ICI treatment and overall survival (OS), since initiation of ICI .
4c3880bb027f159e801041b1021e88e8 Result
51 patients were included from 20 centers in France: 100% adenocarcinoma, 60.7% never smokers, 58.8% female, 58 ± 8.8 years age at diagnosis (36-83), 82.3% EGFR mutated, 15.7 % and 2% ALK and ROS 1 translocated respectively. ICI was a third line treatment in 35,3% of cases, a fourth and more lines treatment in 64,7% of cases. Median PFS was 2.1. [95% CI: 1.5-3.2] months for the whole population, 2.15 [95% CI: 1.4-3;2], for EGFR patients and 2.4 [95% CI: 2.1; NR] for ALK tranlocated patients; 3 months-PFS were 37,3% [95% CI: 26.1; 53.2]; 8 weeks ORR were 19.6% (10 pts with partial response). The median OS for the whole population was 14.7.[95%CI: 12.1-19.2] months, 13.9 [95% CI: 8.8-20] for EGFR patients, 19.2. [95% CI: 13.1-NR] for ALK translocated; 7 (13.7%) patients were treated more than 9 months by ICI; 21.6% (11/51) of patients reported toxicities, all < grade3.
8eea62084ca7e541d918e823422bd82e Conclusion
In this real-world setting analysis, efficacy of ICI in EGFR, ALK, ROS1 NSCLC patients appears close to the efficacy observed in pretreated unselected NSCLC patients. Large prospective studies are needed in these populations
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P1.04-35 - Quick Progression (QP) in Patients Treated by Nivolumab (IO) in 2nd Line or More for Non-Small Cell Lung Cancer: ERORECI Study (GFPC 2016-04) (ID 11936)
16:45 - 18:00 | Author(s): Isabelle Monnet
- Abstract
Background
Nivolumab has been approved in 2nd line for advanced non-small cell lung cancer (NSCLC). However, more than half of the patients had progressive disease at 16 weeks, without any response and sometimes with deleterious progressions. This descriptive prospective study aimed to assess the characteristics of non responders with QP after IO and the following treatments.
a9ded1e5ce5d75814730bb4caaf49419 Method
From September 1st, 2016 to August 31th, 2017, patients (pts) treated by IO (second line or more) with QP<16 weeks were included by 20 GFPC centers. NSCLC characteristics at the diagnosis, at the IO initiation, treatments (before IO, IO and after IO) and outcomes responses, progression free survival (PFS) according to lines of treatments were recorded.
4c3880bb027f159e801041b1021e88e8 Result
The sample included 319 pts: 64,3y± 9,6, smokers/ex-smokers: 48.0%-42.9%, male: 70.8%, PS01/2: 92.8%-7.2%, stage IV at diagnosis: 71.8%; adenocarcinoma: 63.9%. K-Ras mutated: 25.7%. Only 29% of patients had a PDL1 determination. 93% of pts received first line therapy, 32% second line, 10.3% third line before IO. First line PFS (PFS1) was 6.9m [6.43-7.8], PFS2: 9.33m [1.2-19], PFS3: 4.1m [1.56-12.43]. PFS for IO was 1.7m [0.76-4.16]. 229 (71,8%) patients had a IO PFS<2m; 14.7% of these patients stopped the treatment for toxicity. Among the 146 pts evaluable for response, PR was found in 23% of cases, SD in 30%, and PD in 47%.The table describe a comparison between two groups of QP during IO.
8eea62084ca7e541d918e823422bd82e Conclusion
In real life, QP during IO remains a challenge in NSCLC. Multivariate analyses will be presented to characterize these patients.
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In collaboration with the GFPC* team and supported by an academic grant from Pierre-Fabre pharmaceuticals.
*GFPC: French Lung Cancer Group
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P1.09 - Pathology (Not CME Accredited Session) (ID 941)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.09-02 - PD-L1 Expression Pattern in Large Cell Neuroendocrine Carcinoma of the Lung: The GFPC 03-2017 "EPNEC" Study. (ID 11945)
16:45 - 18:00 | Author(s): Isabelle Monnet
- Abstract
Background
Large cell neuroendocrine carcinomas of the lung (LCNECs) are rare neoplasms with few therapeutics options especially for stage IV diseases. Pathological diagnostic of LCNECs may be difficult with low interobserver reproducibility and need immunohistochemical (IHC) staining. Immune checkpoint inhibitors targeting tumoral and immune cells interaction have revolutionized the treatment of NSCLC, but few data's are available on LCNECs immune environment and particulary the expression of PD-L1 on both tumors (TC) and immune infiltrating (IC) cells. The objective of the present study is to determine the pattern of PD-L1 staining in a cohort of LCNECs patients.
a9ded1e5ce5d75814730bb4caaf49419 Method
Clinical files and tumors biopsies of patients (pts) with a LCNEC diagnosed between 01.01.2014 and 31.12.2016 were retrospectively collected (GFPC 03-2017). All histological samples were centrally reviewed by a panel of six independent pathologists, according to the WHO 2015 classification. LCNEC was confirmed and PD-L1 expression was determined both in TC and IC, using the anti-PD-L1 antibody 22C3 (kit and automat Dako). PD-L1 expression was scored on TC as the percentage of PD-L1 positive cells (0 to 100%). PD-L1 expression on IC was determined as follows: IC0: positive IC representing<1% of the tumor surface; IC1: positive IC representing>=1% but<5% of the tumor surface; IC2: positive IC representing>=5% but<10% of the tumor surface; and IC3: positive IC representing>10% of the tumor surface.
4c3880bb027f159e801041b1021e88e8 Result
Eighty-six pts were initially included in the study.Twenty-eight (32%) of them were excluded for non-LCNEC diagnosis after review. Among the 58 remaining pts with confirmed LCNEC, five (8%) had a mixed histology with a NSCLC component.The mean age of the population was 65 years, mainly mens (86%) and former or current heavy smokers (93%). Fifty-five and 51 tumors samples were respectively available for TC and IC PD-L1 IHC expression. PD-L1 expression on TC was found in only 12% of the samples (7/55), while 76% (39/51) of the samples shows IC PD-L1 positive, with respectively 18 (35%) IC3, 8 (14%) IC 2, and 13 (25%) IC1.
8eea62084ca7e541d918e823422bd82e Conclusion
Histological diagnosis of LCNEC remains difficult, and prospective studies concerning patients with LCNEC should include a centrally pathological review of tumors.The PD-L1 expression pattern looks different for LCNEC in comparison to other lung carcinomas, as few TC were found positive although IC were frequently positive, half of the tumors having high PD-L1 IC infiltration (IC3/2). This PD-L1 pattern may suggest a potential effectiveness of therapeutic anti PD-L1 antibodies and this hypothesis have to be adressed in clinical trials.
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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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P1.13-09 - Efficacy and Tolerance of Osimertinib in Real Word Setting: Results of the French Early Access Program (EXPLORE T790M GFPC Study). (ID 11335)
16:45 - 18:00 | Author(s): Isabelle Monnet
- Abstract
Background
Based on the Phase III AURA3 trial, osimertinib a third-generation EGFR TKI is approved in France in EGFR T790M-positive advanced NSCLC whose disease have progressed on or after first or second generation EGFR TKI.
Objective: to assess efficacy and tolerance of Osimertinib in real world setting.
a9ded1e5ce5d75814730bb4caaf49419 Method
Retrospective, multicentric study including T790M-positive advanced NSCLC receiving osimertinib from 07 April 2015 to 27 April 2016 in French early access program. Overall survival (OS) and progression free survival PFS) were analyzed in the whole population, in the subgroup of patients with cerebral metastasis at osimertinib initiation and according to the number of previous treatment lines (1 versus 2 or more).
4c3880bb027f159e801041b1021e88e8 Result
The analysis included 205 patients treated in 52 centers; mean age 69.5 ± 11.1 years, female 68.8%, adenocarcinoma 97.5%, EGFR mutations exons 19/21: 66.5%/ 30.5%, never smokers 71.5 %, PS 0-1/2/ 3-4: 54%/18,8%/27.2%, stage IV: 87.4%,presence of cerebral metastasis at osimertinib initiation: 43.7% .
EGFR T790M mutation diagnosis have been done by liquid biopsy in 34.4 % or on tissue re-biopsy in 65.6%. Patients received a median of 2.8 ± 1.5 lines of treatment before osimertinib initiation. All patients received a first or second generation EGFR TKI before osimertinib. Osimertinib has been used in second line setting in 18% of cases and in third line or more setting in 82%.
Median PFS was 12.4 (CI 95%: 10.1-15.1) months in the whole population, 9.7 (CI 95%: 7.7-13.5) in patients with cerebral metastasis and 15.8 (CI 95%: 11.9-17) months in patients without cerebral metastasis, (p : 0.2). PFS was not significantly different according to the use of osimertinib as second or third line of treatment: 12.6 (CI 95%: 6.7-17.5) vs 12.4 (CI 95%: 9.7-15.3) months, respectively.
Median OS since osimertinib initiation was 20.5 (CI 95%: 16.9-24.3) months, 23.06 [18.56;27.83] and 18.00 [12.16;22.21] months in patients without and with cerebral metastasis, respectively. OS was not significantly different according the use of osimertinib as second or third line of treatment: 17.5 (CI 95%: 11.6;27.8) vs 21.7 (CI 95%: 17.3;24.3) months (p=0.4).
A new biopsy was performed at disease progression on osimertinib in 50 patients: data will be presented.
8eea62084ca7e541d918e823422bd82e Conclusion
Efficacy of Osimertinib in real world setting appears similar to that observed in clinical trials in patients with EGFR T790M mutation in ≥2ndline.
Clinical trial information: Supported by an academic grant from Astra Zeneca
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P2.15 - Treatment in the Real World - Support, Survivorship, Systems Research (Not CME Accredited Session) (ID 964)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Track:
- Presentations: 1
- Moderators:
- Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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P2.15-29 - Eligibility for Anti-Angiogenic Treatments in Patients with Squamous Non-Small Cell Lung Cancer (SQ-NSCLC): EPISQUAMAB Study (GFPC 2015-01) (ID 11338)
16:45 - 18:00 | Author(s): Isabelle Monnet
- Abstract
Background
Antiangiogenic treatments are today restricted to non-squamous NSCLC. New drugs, like ramucirumab, have been approved in second line setting for advanced NSCLC regardless histology but there is little information about the rate of squamous NSLC eligible to these treatments. This descriptive, prospective, observational study aimed to assess the rate of squamous advanced NSCLC patients eligible to anti-angiogenic treatments.
a9ded1e5ce5d75814730bb4caaf49419 Method
Each participating center had to include consecutive relapsed advanced SQ-NSCLC and to assess the presence of common criteria which restricted the use of antiangiogenic treatments (hemoptysis, cardiovascular diseases, tumoral extension to blood vessels and tumoral cavitation).
4c3880bb027f159e801041b1021e88e8 Result
From july 2016 to july 2017, 317 patients were included: 256 (80.8%) men, PS0/1/2 in 30.5%/54.5%/14.9% patients, stage IV in 74.5% of cases. Ineligibility criteria for anti-angiogenic therapy were found in 53.6% of patients (one single criteria in 29,3%, two criteria in 19,9%, three in 3.5%). The main reasons for ineligibility was as followed: blood vessel extension 39.8%, cavitation 20.5%, hemoptysis 7.2%, cardiovascular diseases 12.1%.
Table described patients characteristics according to the ineligibility criteria: Cavitation had the highest number of metastatic disease, cardiovascular diseases the highest number of men and number of metastatic site.
8eea62084ca7e541d918e823422bd82e Conclusion
In a non-selected advanced SQ-NSCLC population, only half of these patients are ineligible to a second line anti-angiogenic treatments with a wide majority of tumoral blood vessel extensions and cavitations.
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In collaboration with the GFPC* team and supported by an academic grant from Lilly pharmaceuticals.
*GFPC: French Lung Cancer Group
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