[Bronchoscopic COPD treatments]. / Traitements endoscopiques de la BPCO.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with disabling respiratory symptoms including dyspnea, frequent exacerbations and chronic bronchitis. The currently available pharmacological and non-pharmacological therapies have limited efficacy, necessitating the development of interventional strategies, many of them endoscopic. STATE OF THE ART: Endoscopic lung volume reduction has markedly increased over recent years, principally as regards the endobronchial valves currently used in routine care. Indeed, multiple randomized trials have demonstrated a significant clinical benefit in a selected population identifiable due to the absence of interlobar collateral ventilation. Other endoscopic volume reduction techniques (polymers, thermal vapor, spirals) shall require additional studies before being considered as options in routine care. Targeted lung denervation (TLD) has aroused interest as a means of reducing exacerbations in the early phases of relevant studies. Endobronchial techniques (bronchoscopic cryospray, bronchial rheoplasty) are still at a very early stage of development, which is aimed at reducing the symptoms of chronic bronchitis. OUTLOOK: Aside from endobronchial valves, which are currently employed in routine care, all the above-mentioned endoscopic techniques require additional studies in order to determine their benefit/risk balance and to identify the population that would benefit the most. CONCLUSIONS: Endoscopic treatments constitute a major avenue of research and innovation in the therapeutic management of COPD. Inclusion of patients in disease registries and clinical trials remains essential, the objective being to gauge the interest of these treatments and their future role in everyday COPD management.

Lorlatinib for advanced ROS1+ non-small-cell lung cancer: results of the IFCT-1803 LORLATU study.

INTRODUCTION: ROS1-rearranged (ROS1+) non-small-cell lung cancer (NSCLC) is a rare lung cancer with limited treatment options. Phase I-II studies with ROS1-tyrosine kinase inhibitors (TKIs) included small numbers of patients and real-world data are lacking. We investigate the efficacy and safety of lorlatinib, a third-generation TKI targeting ALK and ROS1, in patients with ROS1+ NSCLC treated through an expanded access program. METHODS: Consecutive patients with advanced ROS1+ NSCLC treated with lorlatinib between October 2015 and June 2019 were included. Data were collected from medical records. The primary endpoint was progression-free survival. RESULTS: Out of the 80 patients included, 47(59%) were female, 49(62%) never smokers (less than 100 cigarettes over the lifetime), and 68(85%) had stage IV NSCLC at diagnosis. Most frequent histology was adenocarcinoma (95%) and median age was 58.2 years. At the time of lorlatinib initiation, 51(64%) patients had brain metastases and 55(81%) were PS 0-1. Lorlatinib was administered as second/third/fourth/fifth+ line in 29%/28%/18%/26% of patients. All patients previously received at least one ROS1 TKI, and 55(69%) previously received chemotherapy. Median follow-up from lorlatinib initiation was 22.2 months. Median progression-free survival and overall survival from lorlatinib initiation were 7.1 months [95% confidence interval (CI) 5.0-9.9 months] and 19.6 months (95% CI 12.3-27.5 months). Median duration of treatment with lorlatinib was 7.4 months (95% CI 6.5-13.1 months). Overall response and disease control rates were 45% and 82%, respectively. The central nervous system response rate was 72%. Treatment was stopped due to toxicity in 10 patients (13%). The safety profile was consistent with previously published data. CONCLUSIONS: Lorlatinib is a major treatment option for advanced refractory ROS1+ NSCLC in treatment strategy.