Showing papers by "David Planchard published in 2014"
TL;DR: AZD9291 is a selective, third generation EGFR-TKI, effective against both EG FR sensitizing and resistance T790M mutations in preclinical models, and is conducting a phase I clinical trial.
Abstract: 8009^ Background: AZD9291 is a selective, third generation EGFR-TKI, effective against both EGFR-TKI sensitizing and resistance T790M mutations in preclinical models. We are conducting a phase I st...
133 citations
TL;DR: In this paper, the authors explored whether KRAS mutations could impact tumor response, and disease control rate (DCR) to first-line platinum-based chemotherapy (CT) as well as progression-free survival (PFS) or overall survival (OS).
41 citations
University of Duisburg-Essen1, National Taiwan University2, Samsung Medical Center3, Taipei Veterans General Hospital4, European Institute of Oncology5, Seoul National University Hospital6, Shanghai Jiao Tong University7, Tongji University8, Boehringer Ingelheim9, Yonsei University10, Institut Gustave Roussy11
TL;DR: In this article, the authors evaluated the efficacy of continuation of the irreversible ErbB family blocker, afatinib (A), beyond progression with the addition of P in NSCLC pts with prior benefit from reversible EGFR tyrosine kinase inhibitors (E/G) and A.
Abstract: 8019^ Background: Improved disease control with continuation of EGFR inhibition beyond progression has been suggested in retrospective/non-randomized studies, however, this has yet to be prospectively evaluated in a randomized trial. LL5 is a randomized trial, which assessed the efficacy of continuation of the irreversible ErbB family blocker, afatinib (A), beyond progression with the addition of P in NSCLC pts with prior benefit from reversible EGFR tyrosine kinase inhibitors (E/G) and A. Methods: In this open-label, global phase III trial, pts with NSCLC who had failed ≥1 line of CT and E/G (after ≥12 wks treatment) were treated with A (50 mg/day) in Part A (n=1154). Upon progression, those with ≥12 wks on A were eligible to be randomized 2:1 to A+P (40 mg/day; 80 mg/m2/week) or single agent investigator’s choice CT in Part B. Primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), overall survival (OS), and safety. Results: 202 pts were randomiz...
30 citations
Institut Gustave Roussy1, Seoul National University Hospital2, Memorial Sloan Kettering Cancer Center3, Aix-Marseille University4, VU University Amsterdam5, University Medical Center Groningen6, Johns Hopkins University7, Yonsei University8, University of Pittsburgh9, GlaxoSmithKline10, Research Triangle Park11, Harvard University12
TL;DR: Dabrafenib is the first drug of its class to show activity in a prospective trial of NSCLC with BRAF mutations, and demonstrated significant antitumor activity with durable objective responses and acceptable safety profile.
27 citations
Emory University1, Institut Gustave Roussy2, University of North Carolina at Chapel Hill3, Roswell Park Cancer Institute4, Vanderbilt University5, University of Rennes6, Ohio State University7, University of California, Davis8, Lehigh Valley Hospital9, Bristol-Myers Squibb10, Memorial Sloan Kettering Cancer Center11
21 citations
National Taiwan University1, Seoul National University Hospital2, Institut Gustave Roussy3, Emory University4, Samsung Medical Center5, Asan Medical Center6, National Cheng Kung University7, Vanderbilt University8, Hebron University9, Yonsei University10, AstraZeneca11, University of Manchester12, Harvard University13
TL;DR: AZD9291 has been well tolerated at all dose levels tested and clinical activity has been shown in pts with centrally confirmed EGFR T790M+ NSCLC, with durable responses of >6 months.
17 citations
TL;DR: In this article, the authors used a log-rank test to investigate the association between toxicity profile, overall survival (OS) and progression free survival (PFS) using Kaplan-Meier and their association with baseline characteristics.
7 citations
TL;DR: Plasma levels of EGFR-TKI-sensitising mutations correlate more closely with tumour genotype than T790M, likely due to the greater genomic heterogeneity of resistance.
6 citations
TL;DR: In this small group of pts with SCC, the authors observed prolonged PFS, higher OR and trend towards longer OS in patients treated with A + P vs IC following A, and signs of activity in this difficult-to-treat population are encouraging.
5 citations
Institut Gustave Roussy1, Samsung Medical Center2, National Taiwan University3, Yonsei University4, European Institute of Oncology5, Taipei Veterans General Hospital6, Shanghai Chest Hospital7, University of Münster8, Academy of Military Medical Sciences9, Boehringer Ingelheim10, University of Duisburg-Essen11
TL;DR: A + P showed trends for symptom improvement and delayed TTD vs IC in heavily-pretreated NSCLC patients and GHS/QoL was maintained over time despite a doubling of median treatment time and PFS with A + P.
4 citations
TL;DR: Initial assessment of key demographic factors indicated no relationship between any demographic factor and PK, and PK results support once daily dosing, the same dose for all ethnic populations and switching from capsule to tablet in future studies.
01 Jan 2014
TL;DR: Gender Female 99 (50%) 10 (27%) 40 (57%) 149 (49%) 11 (35%) 16 (13%) 22 (37%) 9 (26%) 32 (53%)
Abstract: 198 (100%) 22 (59%) 70 (100%) 290 (95%) 19 (61%) 73 (60%) 0 (0%) 0 (0%) 60 (100%) SCC 0 (0%) 15 (41%) 0 (0%) 15 (5%) 12 (39%) 49 (40%) 59 (100%) 35 (100%) 0 (0%) Stage 1A 96 (48%) 9 (24%) 33 (47%) 138 (45%) 0 (0%) 112 (92%) 21 (36%) 6 (17%) 22 (37%) 1B 102 (52%) 28 (76%) 37 (53%) 167 (55%) 31 (100%) 10 (8%) 38 (64%) 29 (83%) 38 (63%) Gender Female 99 (50%) 10 (27%) 40 (57%) 149 (49%) 11 (35%) 16 (13%) 22 (37%) 9 (26%) 32 (53%)
TL;DR: Practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with cezotinib.
Abstract: Crizotinib (XALKORI(™), Pfizer) is a tyrosine kinase inhibitor of ALK, MET, and ROS1, which is currently approved for the second line treatment for ALK-rearranged lung cancer. This work from an expert group, based on the review of the data from the Profile studies, aims to provide practical elements in order to optimize the tolerability of crizotinib. Specific major or frequent side effects of crizotinib are discussed: visual disturbances, cardiac effects, elevated transaminases, and hypogonadism. In the routine practice, patients should be advised about visual disturbances, especially with regard to driving in low brightness. Digestive disorders related to crizotinib are exceptionally persistent or severe. Dietary measures and symptomatic treatments usually control these disorders. It is recommended to perform an electrocardiogram before introduction of crizotinib, to identify prolonged QT interval. Torsades de pointes may produce dizziness or syncope. Hypogonadism should be considered in case of fatigue, decreased libido, and even depression, taking into account that these symptoms may be related to cancer; testosterone serum level should be measured to identify patients that may be eligible to receive a supplementation. Monitoring of liver function tests, including transaminases and bilirubin, is necessary. To conclude, these practical elements are helpful to optimize treatment with crizotinib in patients with ALK-rearranged lung cancer; in the future, academic initiatives should be taken to study these aspects, based on the monitoring of large cohorts of patients treated with crizotinib.
TL;DR: This trial is aimed at elucidating whether or not adding anti-CTLA-4 therapy to existing Gef would complement and enhance its effects and to establish a recommended phase 2 dose.
TL;DR: Prophylactic irradiation of chest scars and drains is validated by French guidelines and the diagnosis of MPM is based on histology and on biopsies best obtained by thoracoscopy.
Abstract: Le mesotheliome pleural malin (MPM) est une tumeur rare et agressive, souvent consecutive a une exposition professionnelle a l’amiante. La symptomatologie clinique et radiologique est aspecifique. Le diagnostic est apporte par l’histologie a partir de biopsies pleurales obtenues par thoracoscopie. L’irradiation des orifices chirurgicaux diagnostiques est validee par les recommandations francophones. La chirurgie par pleuropneumonectomie elargie ou par pleurectomie/decortication n’est pas recommandee en dehors d’un essai clinique. La chimiotherapie par la combinaison pemetrexed-cisplatine est le traitement de reference du MPM. Le bevacizumab est evalue dans l’essai de phase III MAPS dont les 445 inclusions se sont terminees en decembre 2013.
01 Jan 2014
TL;DR: The fact that the model is robust in 3 lung adenocarcinoma data sets but fails to accurately predict the outcome in LCC & SCC patients is indicative of an underlying biological heterogeneity and validates the choice to restrict the population to one tumor type only.
Abstract: 2. Biological significance From the 9 genes used in our model (not disclosed here), 8 of them have been reported to be linked with key oncogenic processes. Alterations have been reported for all 9 genes in TCGA lung adenocarcinoma patients (n= 129). Genes were altered in 31% of cases and alterations tended to be mutually exclusive. The fact that the model is robust in 3 lung adenocarcinoma data sets but fails to accurately predict the outcome in LCC & SCC patients is indicative of an underlying biological heterogeneity and validates our choice to restrict our population to one tumor type only.