Virtual Library
Start Your Search
Alexis B Cortot
Author of
-
+
MA 03 - Chemotherapy (ID 651)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Jin-Hyoung Kang, W. Su
- Coordinates: 10/16/2017, 11:00 - 12:30, Room 502
-
+
MA 03.10 - Prognostic Factors in NSCLC Patients Treated with a Fourth-Line Therapy (ID 7455)
12:05 - 12:10 | Author(s): Alexis B Cortot
- Abstract
- Presentation
Background:
Emergence of new active drugs and improvement in supportive care make it more likely for patients with advanced NSCLC to receive a fourth-line therapy.However, no survival benefit of such treatment has ever been demonstrated yet, although some studies suggest that it may be effective in selected patients. A better selection could avoid exposing patients to futile and toxic treatments. We conducted a study aiming at identifying prognostic factors in patients with advanced NSCLC treated with a fourth-line therapy.
Method:
In this retrospective, multicentric study, patients with advanced NSCLC receiving a fourth-line therapy were included. Factors associated with prolonged overall survival (OS, defined as OS >6 months) were identified by univariate and multivariate analysis using a Forward method.
Result:
151 patients were included in this study between Jan 2015 and Dec 2016. Median age was 60 (range 55-64). Most patients were male (70%) and had adenocarcinoma (72%). Most common prior treatments included platinum-based chemotherapy (92%), single-agent chemotherapy (81%), targeted therapies (46%) and immunotherapy (9%). Median OS was 7.39 months (6.7-9.43). Nine factors were significantly associated with OS >6 months: current smoker (Hazard Ratio (HR) 1.99, 95% confidence interval[1.16-3.41]), former smoker (HR 0.51[0.30-0.98]), Karnofsky Index (KI) ≥ 90% at the start of fourth-line therapy (HR 0.35[0.19-0.65]), weight loss since first-line therapy (HR 1.85[1.06-3.23]), early stage at diagnosis (HR 0.48[0.24-0.96]), number of cycles and delay since first-line therapy (HR 0.94[0,89-0,99]and 0.99[0.99-1]), Progressive Disease (PD) as Best Objective Response (BOR) in the first 3 lines of treatment (HR 2.92[1.9-5.37]), absence of grade ≥ 3 Adverse Events (AEs) during first-line therapy(HR 0.54[0.31-0.94]). Among them, 4 independent variables were found to be statistically significant by multivariate analysis, including early stage at diagnosis (HR 0.37[0.16-0.58]), absence of grade ≥ 3 AEs during first-line therapy (HR 0.56[0.32-0.98]), PD as BOR in the first 3 lines of treatment (HR 3.06[1.64 -5.73]) and KI ≥ 90% at the start of fourth-line therapy (HR 0.31[0.16-0.58]).
Conclusion:
We highlighted 4 factors significantly associated with OS >6 months in patients treated with fourth-line advanced NSCLC. These factors need to be prospectively assessed to confirm if they could help identifying patients who may benefit from fourth-line therapy.
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.
-
+
MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
-
+
MA 07.06 - Detection of Mechanisms of Resistance to ALK Inhibitors in Routine Practice: A Retrospective Study (ID 8942)
16:20 - 16:25 | Author(s): Alexis B Cortot
- Abstract
- Presentation
Background:
Treatment of ALK-rearranged Non-Small Cell Lung Cancer (NSCLC) relies on ALK tyrosine kinase inhibitors (TKI). However, efficacy of ALK TKI is limited by the emergence of drug resistance. ALK molecular alterations (amplification or mutation) account for about 40% of mechanisms of resistance to ALK TKI. Even though clinical and fundamental data suggest variability in drug efficacy according to the mechanism of resistance, these mutations are rarely investigated in routine practice. While targeted next-generation sequencing (t-NGS) is increasingly used for detecting molecular abnormalities, the impact of this tool in routine detection of ALK alterations is unknown.
Method:
We performed a retrospective multicentric study aiming at determining the frequency of ALK alterations using t-NGS in metastatic ALK-rearranged NSCLC patients progressing upon ALK TKI. Clinical, pathological, molecular characteristics, and patients outcome were collected.
Result:
We identified 22 patients with metastatic ALK-rearranged NSCLC who underwent a rebiopsy at progression on first ALK TKI, between January 2012 and May 2017. There were 12 females and 10 males, median age was 55, 18 patients (82%) were never smokers. Crizotinib was the first ALK TKI in 21 patients (95%). 15 patients (68%) received a second-generation ALK inhibitor and 3 patients (14%) received a third generation of ALK inhibitor. t-NGS on rebiopsy was performed in 16 patients. 6 ALK mutations (37.5%) were identified, including 3 G1202R, 1 C1156Y, 1 V1180L and 1 L1196M mutations . An ALK amplification (6%) was detected in a rebiopsy (6%) by FISH, with no concomitant ALK mutation. All ALK mutations were detected in solid biopsy, 2 ALK mutation was also detected in liquid biopsy. Median Overall Survival from first ALK TKI was 797 days (IC 95% 460-1135) and tended to be longer in patients with a known mechanism of resistance (1135 days Vs 543 days p=0.2).
Conclusion:
Targeted NGS is feasible in routine practice for detection of mechanisms of resistance to ALK TKI in ALK-rearranged NSCLC patients and may help selecting the best treatment at progression upon ALK TKI.
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.
-
+
P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P3.02-002 - Liquid and Solid Rebiopsies in EGFR-Mutated NSCLC Patients (ID 8442)
09:30 - 09:30 | Presenting Author(s): Alexis B Cortot
- Abstract
Background:
Treatment of EGFR-mutated NSCLC patients with acquired resistance to EGFR tyrosine kinase inhibitors (TKI) relies on identification of the mechanism of resistance.
Method:
We performed a retrospective multicentric study in order to investigate use and results of liquid (circulating free DNA) and solid rebiopsies in routine practice.
Result:
We included 95 EGFR-mutated NSCLC patients with at least one rebiopsy after treatment with EGFR TKI (mostly 1[st] generation TKI). 87 solid rebiopsies and 71 liquid rebiopsies were performed. The number of liquid biopsies increased over time, from 1/y (6,6% of all rebiopsies in 2014) to 53/y (70,6% of all rebiopsies in 2016). The proportion of liquid biopsies increased with the number of rebiopsies per patient, from 35,5% for the first rebiopsy to 83,3% for the third rebiopsy. The rebiopsy identified a mechanism of acquired resistance in 48 patients (50,5%), including 43 patients with a T790M mutation (45,2%), 2 patients (2,1%) with MET amplification, 1 patient (1%) with small cell lung cancer transformation, 1 patient (1%) with a C797S mutation and 1 patient (1%) with a KRAS mutation. The initial EGFR mutation was found in 74 solid rebiopsies (85%) and 43 liquid rebiopsies (60%). The T790M mutation was found in 32 solid rebiopsies (36,8%) and 18 liquid rebiopsies (25,3%). Among 44 patients having both liquid and solid rebiopsies performed at the same time, an EGFR mutation was found by both techniques in 26 cases (59,1%) and the overall concordance was 88,6%. Analysis of cerebrospinal fluid was positive in 10 patients (100%) for the initial EGFR mutation and 1 patient (10%) for the T790M mutation. A T790M mutation was identified in 37,3% of all first rebiopsies. Repeated rebiopsies when the first biopsy was negative identified the T790M mutation in 29,6% of cases.
Conclusion:
In our series representative of daily practice, rebiopsies of EGFR-mutated NSCLC patients with acquired resistance to EGFR TKI identified a mechanism of resistance in half of the cases. Repeating rebiopsies increased the chance of detecting a T790M mutation.
