2018 ASCO Annual Meeting!
Session: Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
Type: Oral Abstract Session
Time: Friday June 1, 2:45 PM to 5:45 PM
Biomarker-driven access to crizotinib in ALK, MET, or ROS1 positive (+) malignancies in adults and children: The French National AcSé Program.
Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics
2018 ASCO Annual Meeting
J Clin Oncol 36, 2018 (suppl; abstr 2504)
Author(s): Gilles Vassal, Nathalie Cozic, Gilbert Ferretti, Sophie Taieb, Roch Houot, Laurence Brugieres, Thomas Aparicio, Jean-Yves Blay, Ivan Bieche, Sylvie Lantuejoul, Celine Mahier - Ait Oukhatar, Natalie Hoog Labouret, Denis Moro-Sibilot; Gustave Roussy, Villejuif, France; Biostatistics Unit, Gustave Roussy Cancer Campus, Villejuif, France; Centre Hospitalier Universitaire, Grenoble, France; Centre Oscar Lambret, Lille, France; Centre Hospitalier Universitaire Pontchaillou, Rennes, France; Department of Gastroenterology, Saint Louis Hospital, Paris, France; Centre Léon Bérard, Lyon, France; Institut Curie, Paris, France; Centre Léon Bérard, Lyon, FR; Unicancer, Paris, France; French National Cancer Institute (INCa), Boulogne-Billancourt, France; Grenoble University Hospital, Grenoble, France
Background: Crizotinib (czb) is registered for the treatment of patients (pts) with ALK+ or ROS1+ lung cancer. Czb targets (ALK, MET, ROS1) are also altered (translocation [tlc], amplification [amp], mutation [mut]) in a wide range of malignancies (malg.) in adults and children. To generate high evidenced-based knowledge and to prevent off-label use, the French National Cancer Institute (INCa) launched the AcSé Program: equal access to tumor molecular diagnosis along with an exploratory phase II trial, to allow for a nationwide safe and controlled access to czb outside its indication. Methods: Biomarker identification was proposed to pts ≥ 1 year old (yo) with an advanced disease among more than 15 malg. known to harbor a czb target alteration. If not eligible for any other trial, pts may enter one of the 22 cohorts defined by the type of tumor and target. Tumor response was evaluated every 2 months (mo) using RECIST criteria v1.1. The primary endpoint is the objective response rate (ORR) at 2 mo [complete + partial response]. A two-stage Simon design is applied to each cohort. Results: From 08/2013 to 12/2017, 12836 pts from 186 centers have entered the biomarker program. Alterations found in pts were: ALK tlc, mut, amp in 14/2053, 8/306, 10/1846; MET amp ( > 6 copies/diploid genome) in 392/7847 [250/4127 NSCLC, 60/1232 glioblastomas, 28/939 colon, 33/546 esogastric, 7/635 ovarian, 3/82 kidney cancers]; MET mut in 98/2697; ROS1 tlc in 80/4625 [NSCLC, cholangiocarcinoma, inflammatory myofibroblastic tumor (IMT)]. Clinical trial information: NCT02034981 Overall, 235 pts (median age, 58 yo [1–92]) received czb (adult 250 mg bid; child 280 mg/m² bid). Conclusions: Czb displayed a wide antitumor activity in several MET, ALK and ROS1+ malg. Equal and safe access across France to molecular testing and targeted therapies outside their approved indication is feasible.
|Positive cohorts||Pts analyzed||CR/PR||ORR % [IC95%]|
|ALCL ALK tlc||22||12||54 [34-75]|
|NSCLC MET amp||25||6||24 [7-40]|
|ROS1 tlc||37||20||54 [40-70]|
|MET mut||27||6||22 [7-38]|
|Esogastric MET amp||8||3||37 [10-74]|
|IMT ALK tlc / ROS1 tlc||7||1||28 [5-70]|