Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry.

BACKGROUND: Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. PATIENTS AND METHODS: We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. RESULTS: We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). CONCLUSIONS: : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.

Severe SARS-CoV-2 pneumonia: Clinical, functional and imaging outcomes at 4 months.

INTRODUCTION: Given the pathophysiology of coronavirus disease 19 (COVID-19), persistent pulmonary abnormalities are likely. METHODS: We conducted a prospective cohort study in severe COVID-19 patients who had oxygen saturation<94% and were primarily admitted to hospital. We aimed to describe persistent gas exchange abnormalities at 4 months, defined as decreased diffusing capacity of the lungs for carbon monoxide (DLco) and/or desaturation on the 6-minute walk test (6MWT), along with associated mechanisms and risk factors. RESULTS: Of the 72 patients included, 76.1% required admission to an intensive care unit (ICU), while 68.5% required invasive mechanical ventilation (MV). A total of 39.1% developed venous thromboembolism (VTE). After 4 months, 61.4% were still symptomatic. Functionally, 39.1% had abnormal carbon monoxide test results and/or desaturation on 6MWT; high-flow oxygen, MV, and VTE during the acute phase were significantly associated. Restrictive lung disease was observed in 23.6% of cases, obstructive lung disease in 16.7%, and respiratory muscle dysfunction in 18.1%. A severe initial presentation with admission to ICU (P=0.0181), and VTE occurrence during the acute phase (P=0.0089) were associated with these abnormalities. 41% had interstitial lung disease in computed tomography (CT) of the chest. Four patients (5.5%) displayed residual defects on lung scintigraphy, only one of whom had developed VTE during the acute phase (5.5%). The main functional respiratory abnormality (31.9%) was reduced capillary volume (Vc<70%). CONCLUSION: Among patients with severe COVID-19 pneumonia who were admitted to hospital, 61% were still symptomatic, 39% of patients had persistent functional abnormalities and 41% radiological abnormalities after 4 months. Embolic sequelae were rare but the main functional respiratory abnormality was reduced capillary volume. A respiratory check-up after severe COVID-19 pneumonia may be relevant to improve future management of these patients.

[Use of endobronchial ultrasound in the management of cryptogenic haemoptysis]. / Apport de l'échoendoscopie radiaire dans la prise en charge de l'hémoptysie cryptogénique.

Currently about 50% of cases of haemoptysis are thought to be cryptogenic. Haemorrhage from the pulmonary arterial system is rare and usually due to aneurysms or pseudoaneurysms, the radiological diagnosis of which is often difficult. We report here the case of a patient admitted with a heavy haemoptysis in whom the thoracic CT scan did not reveal the diagnosis. Bronchoscopy with endobronchial ultrasound showed a vascular malformation of a branch of the pulmonary artery allowing a radiological embolisation. This case underlines the importance of bronchoscopy and the role of ultrasound in the diagnosis of haemoptysis, considered ideopathic, complicating vascular malformations.