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Here we report our experience of ceritinib in crizotinib-pretreated patients with anaplastic lymphoma kinase (ALK) positive (ALK+) 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 ALK+ or ROS proto-oncogene 1 positive (ROS1+) tumours. Patients received oral ceritinib (750 mg·day−1 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 ALK+ NSCLC and 13 had ROS1+ NSCLC. The median age of ALK+ 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 ALK+ 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% versus 42.4%) and those receiving prior crizotinib for >5 months (51.6% versus 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−1) demonstrated efficacy similar efficacy to ASCEND-1, ASCEND-2 and phase 3 ASCEND-5 trials with manageable safety in crizotinib-pretreated patients with ALK+ NSCLC., Ceritinib (750 mg per day) showed similar efficacy as in clinical trials in crizotinib-pretreated ALK+ NSCLC patients http://ow.ly/8oXe30h27D0

To the Editor: Somatic epidermal growth factor receptor ( EGFR ) mutations are now routinely integrated in the molecular diagnosis of nonsmall cell lung cancers (NSCLC) [1, 2]. Thus, germ-line EGFR mutations are rarely mentioned or looked for in the context of patients with a family history of cancer, as their association with NSCLC familial cancer risk is not well established. Moreover, the predictive value of these mutations for response to EGFR tyrosine kinase inhibitors (TKIs) is not well known [3]. We report here two different heterozygous germ-line EGFR variants identified in two Caucasian NSCLC patients, who demonstrated different responses to EGFR-TKI. A 63-year-old Caucasian, male former smoker with no family history of cancer (fig. 1a), was admitted for dyspnoea in August 2011, leading to discovery of a lower left lobe lung tumour and pleural effusion. Trans-thoracic biopsy diagnosed an invasive, acinar-predominant adenocarcinoma, classified cT2a N3 M1a (stage IV). Molecular analyses of the tumour by direct sequencing identified two concomitant heterozygous EGFR exon 21 mutations, L858R and V843I, confirmed in two independent experiments (fig. 1b). The V843I variant, but not L858R, was also detected in DNA obtained from a blood sample, with written informed consent, confirming a germ-line mutation (fig. 1c). Following treatment with cisplatin and pemetrexed, the patient relapsed in December 2012 with vertebral metastasis. An EGFR-TKI (erlotinib) was initiated, resulting in a stable disease for 9 months. Figure 1. a–c) Case 1, with epidermal growth factor receptor ( EGFR ) exon 21 mutations (V843I and L858R). a) Pedigree chart. The black case corresponds to the index patient. b) DNA sequencing electrophoretograms for DNA obtained from lung tumour tissue identifying EGFR exon 21 mutations; both mutations are present. c) DNA sequencing electrophoretograms for DNA obtained from blood, identifying one EGFR exon 21 mutation, the V834I variant, is present and confirming …