Real-life experience of ceritinib in crizotinib-pretreatedadvanced non-small cell lung cancer patients

Jacques Cadranel (1) , Alexis B Cortot (2, 3) , Hervé Lena (4) , Bertrand Mennecier , Pascal Do (5) , Eric Dansin (6) , Julien Mazieres (7) , Christos Chouaid , Maurice Perol (8) , Fabrice Barlesi , Gilles Robinet (9) , Sylvie Friard (10) , Luc Thiberville (11, 12) , Clarisse Audigier-Valette , Alain Vergnenegre (13) , Virginie Westeel (14) , Khemaies Slimane , Alexandru Buturuga , Denis Moro-Sibilot (15) , Benjamin Besse (16)

1 Service de Pneumologie = Pneumologie - Oncologie Thoracique - Maladies Pulmonaires Rares [CHU Tenon]
2 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
3 Université de Lille
4 CHU Pontchaillou [Rennes]
5 UNICANCER/CRLC - Centre Régional de Lutte contre le Cancer François Baclesse [Caen]
6 UNICANCER/Lille - Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille]
7 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
8 Centre Léon Bérard [Lyon]
9 CHU - BREST - Hôpital de la Cavale Blanche - CHRU Brest
10 Hôpital Foch [Suresnes]
11 QuantIF-LITIS - Equipe Quantification en Imagerie Fonctionnelle
12 Service de pneumologie, oncologie thoracique et soins intensifs respiratoires [Rouen]
13 Service de Pathologie respiratoire et allergologie [CHU Limoges]
14 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
15 CHU Grenoble
16 Oncologie thoracique

Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase () positive () non-small cell lung cancer (NSCLC) in a French temporary authorisation for use (TAU) study. The French TAU study included crizotinib-pretreated patients with advanced or ROS proto-oncogene 1 positive () tumours. Patients received oral ceritinib (750 mg·day as a starting dose) and best tumour response (as evaluated by the investigator) and safety were reported every 3 months. A total of 242 TAUs were granted from March 12, 2013 to August 05, 2015. Of the 242 patients, 228 had NSCLC and 13 had NSCLC. The median age of patients (n=214) was 58.5 years, 51.9% were female, 70.8% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 and 50.0% had brain metastases. Of the 149 efficacy evaluable NSCLC patients, 5.4% had a complete response (CR), 47.0% had a partial response (PR) and 22.8% had stable disease (SD). At September 05, 2015, the median duration of ceritinib treatment (n=182) was 3.9 months but 5.5 months for patients (n=71) with a follow-up of ≥12 months. Higher objective response rate (ORR) was observed for patients with ECOG PS 0 to 1 (55.0% 42.4%) and those receiving prior crizotinib for >5 months (51.6% 36.1%). Treatment-related adverse events (AEs) were reported in 118 of 208 patients (56.7%), the most common being diarrhoea (22.1%) and hepatic toxicity (19.7%). Ceritinib (750 mg·day) demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase 3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients with NSCLC.

Domains: Life Sciences [q-bio]; Cancer; Life Sciences [q-bio]; Human health and pathology; Pulmonology and respiratory tract; Life Sciences [q-bio]; Pharmaceutical sciences; Medication

Jacques Cadranel, Alexis B Cortot, Hervé Lena, Bertrand Mennecier, Pascal Do, et al.. Real-life experience of ceritinib in crizotinib-pretreatedadvanced non-small cell lung cancer patients. ERJ Open Research, 2018, 4 (1), pp.00058-2017. ⟨10.1183/23120541.00058-2017⟩. ⟨hal-01744408⟩