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A. Gazzah
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MINI 25 - Trials, Radiation and Other (ID 142)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Thymoma, Mesothelioma and Other Thoracic Malignancies
- Presentations: 1
- Moderators:J.M. Clavero, R. Hassan
- Coordinates: 9/08/2015, 16:45 - 18:15, 702+704+706
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MINI25.07 - Clinical Activity of Lucitanib in Advanced Thymic Epithelial Tumours (ID 2153)
16:45 - 18:15 | Author(s): A. Gazzah
- Abstract
- Presentation
Background:
Thymic epithelial tumours are rare malignancies for which there is no standard treatment for patients with advanced disease progressing on or after chemotherapy. Despite the lack of identified targets in thymic malignancies, several studies demonstrated that VEGFR and KIT pathways are the most relevant targets for therapeutic intervention. Lucitanib is an oral, potent, selective inhibitor of the tyrosine kinase activity of FGFR1-3, VEGFR1-3, and PDGFR α/β, all key targets involved in pro-angiogenic and proliferative pathways leading to tumour progression. Therefore, lucitanib could be a potential therapeutic alternative for patients with recurrent or refractory disease.
Methods:
This first in human study is currently evaluating oral lucitanib as monotherapy in various solid tumours. The escalation phase used a 3+3 design in patients with advanced solid tumours to establish the recommended phase II dose. Safety and efficacy were further evaluated in patients whose tumours were determined to be FGF aberrant (FGFR1 and/or 11q amplification) or in patients with tumours known to be anti-angiogenesis-sensitive such as thymic epithelial tumours. In addition, different doses and administration schedules were investigated.
Results:
Of the 134 patients treated in the study, 3 had B-type Thymoma (T) and 12 had Thymic Carcinoma (TC). Among these patients, median age was 54 years [range 37-72], 7 were males and 8 females. Twelve patients (80%) were treated at 12.5mg on daily basis. The other 3 patients (T) received 5, 15 and 20mg respectively. Patients had received a median of 2 previous anti-cancer treatments [range: 0-6]. Median duration of treatment with lucitanib was 7 cycles [range 2-44]. All patients were evaluable for anti-tumour activity according to RECIST v1.1. Two patients had confirmed partial response (1T / 1TC) lasting at least 7 months (TC patient is still ongoing) and 10 patients had a stable disease with 6 of them lasting at least 6 months. To date, 4 patients are still ongoing and receiving benefit from lucitanib independently of the number of previous regimens. The most common adverse events related to lucitanib in this population (all grades, all doses) were hypertension (80%), hypothyroidism (53%), proteinuria (53%) and diarrhoea (40%). There was no major bleeding event reported. These findings were in line with the overall safety profile of lucitanib already described.
Conclusion:
The results of this tumour cohort analysis suggest that lucitanib has signs of clinical activity in patients with advanced thymic epithelial tumours, and should be further investigated in dedicated studies.
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ORAL 06 - Next Generation Sequencing and Testing Implications (ID 90)
- Event: WCLC 2015
- Type: Oral Session
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:G. De Lima Lopes, V. Miller
- Coordinates: 9/07/2015, 10:45 - 12:15, Mile High Ballroom 1a-1f
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ORAL06.05 - Molecular Tumor Board (MTB) in Non-Small Cell Lung Cancers (NSCLC) to Optimize Targeted Therapies: 4 Years' Experience at Gustave Roussy (ID 2563)
10:45 - 12:15 | Author(s): A. Gazzah
- Abstract
- Presentation
Background:
Molecular biology has changed the treatment of advanced NSCLC, leading to many small subgroups of patients (pts) eligible for targeted therapies, many of them being not approved. Since 2010 we created a monthly MTB dedicated to NSCLC pts with potential driving molecular abnormalitie(s). MTB includes expert physicians from the lung tumor board and phase I unit, radiation therapists, researchers, geneticists, pathologists and biologists. A medical report summarizes the findings and treatment recommendations for each pts. We report 4 years of activity of MTB at Gustave-Roussy.
Methods:
All consecutive files discussed in MTB for a NSCLC were reviewed. MTB included pts with at least one molecular alteration based on a 75 gene panel (NGS analysis and FISH for ALK, HER2, MET, FGFR1, ROS1 and RET). Tumor and pts characteristics were collected as well as treatments. Pts outcome was calculated from the MTB date. Kaplan-Meier methods, and Cox proportional hazards models were used for survival analysis, adjusting for sex, histology, smoking status, metastasis at diagnosis, number of line(s) before MTB.
Results:
502 files were discussed between 02/2010 and 09/2014. Median age was 60 yrs (25–88 yrs), 53% were male, 86% Caucasian, 26% never-smokers, and 93% had PS ≤1. Initial clinical stage was III-IV in 417 pts (84%) and 79%/10%/11% were adenocarcinomas/squamous cell carcinomas/others NSCLC. Median number of treatment-lines before MTB was 1 (0-10), 86% were previously treated by a platinum-based chemotherapy regimen, 17% in a therapeutic trial, and median time from diagnosis to MTB was 5 months. Biopsy for Molecular Analysis (MoA) mostly came from CT guided biopsies (62%), surgery (21%) or endoscopy (16%). Biopsy was repeated in 19% of pts to get enough material for MoA. The MoA results were ALK rearrangement in 11%, exon 18/19/20/21 EGFR mutation (mut) in 2/14/4/7% respectively, KRAS mut in 32%, PI3KCA mut in 3%, BRAF mut in 5%, HER2 mut (Exon 20) in 2%, HER2 amplification in 2%, FGFR1 amplification in 3%, MET amplification in 3% and other rare mutations in 27%. MTB recommended a targeted therapy in 344 pts (68%) either within clinical trials (57%), EMA approved therapy (23%), an off label drug (9%), or an expanded access program (11%). 162pts (47%) actually received the recommended therapy, 141 (41%) did not and 41 (12%) might receive it at the time of progression. Median follow-up was 24 months (1-24; follow-up censored after 24 months). Median OS was 13.1 months [95%CI: 8.8; 18.2] for non-oriented pts, and 14.3 months [11.5; 16.7] for oriented pts (p=0.39). We observed a significant difference between EGFR/ALK/ROS1 mutated/rearranged pts (median 23.8 months) vs. pts with KRAS (8.6 months) or others mutations (11.1 months) or non-oriented pts (13.1 m; p=0.0008, HR=0.56, 1.15 and 0.97 respectively compared to non-oriented).
Conclusion:
MTB is feasible in daily practice with treatment recommendations in a majority of NSCLC pts (68%), enrichment in clinical trials or expanded access programs, and limitation of off-label drugs use. Benefit on survival for all oriented pts has to be clarified based on the type of molecular abnormality. Update results will be presented at the meeting.
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