In clinical practice, patients with anaplastic lymphoma kinase (ALK)-rearrangement–positive non–small-cell lung cancer commonly receive sequential treatment with ALK tyrosine kinase inhibitors. The third-generation agent lorlatinib has been shown to inhibit a wide range of ALK resistance mutations and thus offers potential benefit in later lines, although real-world data are lacking. This multicenter study retrospectively investigated later-line, real-world use of lorlatinib in patients with advanced ALK- or ROS1-positive lung cancer. Fifty-one patients registered in a compassionate use program in Austria, who received second- or later-line lorlatinib between January 2016 and May 2020, were included in this retrospective real-world data analysis. Median follow-up was 25.3 months. Median time of lorlatinib treatment was 4.4 months for ALK-positive and 12.2 months for ROS-positive patients. ALK-positive patients showed a response rate of 43.2%, while 85.7% percent of the ROS1-positive patients were considered responders. Median overall survival from lorlatinib initiation was 10.2 and 20.0 months for the ALK- and ROS1-positive groups, respectively. In the ALK-positive group, lorlatinib proved efficacy after both brigatinib and alectinib. Lorlatinib treatment was well tolerated. Later-line lorlatinib treatment can induce sustained responses in patients with advanced ALK- and ROS1-positive lung cancer.

Rationale: The long-term safety and effectiveness of bronchoscopic lung volume reduction with Zephyr endobronchial valves in subjects with severe homogeneous emphysema with little to no collateral ventilation beyond 3 months have yet to be established. Methods: Ninety-three subjects were randomized to either bronchoscopic lung volume reduction with Zephyr valves or standard of care (SoC) (1:1). Zephyr valve subjects were assessed at 3, 6, and 12 months. SoC subjects were assessed at 3 and 6 months; they were then offered crossover to Zephyr valve treatment. Results: The mean group difference (Zephyr valve – SoC) for change in FEV₁ from baseline to 6 months was 16.3 ± 22.1% (mean ± SD; p < 0.001). Secondary outcomes showed the mean between-group difference for the six-minute walk distance of +28.3 ± 55.3 m (p = 0.016); St. George’s Respiratory Questionnaire, −7.51 ± 9.56 points (p < 0.001); modified Medical Research Council, −0.42 ± 0.81 points (p = 0.019); BODE index, −0.85 ± 1.39 points (p = 0.006); and residual volume of −430 ± 830 mL (p = 0.011) in favor of the Zephyr valve group. At 6 months, there were significantly more responders based on the minimal clinically important difference for these same measures in the Zephyr valve versus the SoC group. The clinical benefits were persistent at 12 months. The percentage of subjects with respiratory serious adverse events was higher in the Zephyr valve group compared to SoC during the first 30 days post-procedure but not statistically different for the Zephyr valve and SoC groups from 31 days to 6 months, and stable in the Zephyr valve group out to 12 months. There were 2 deaths in the SoC group in the 31-day to 6-month period and none in the Zephyr valve group out to 12 months. Conclusions: Bronchoscopic lung volume reduction with Zephyr valves in subjects with severe homogeneous emphysema and little to no collateral ventilation provides clinically meaningful change from baseline in lung function, quality of life, exercise capacity, dyspnea, and the BODE index at 6 months, with benefits maintained out to 12 months.

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition with constantly increasing mortality rates. Interleukin (IL)-33 and its decoy receptor, soluble suppression of tumorigenicity 2 (sST2), play a central role in the inflammatory response during infection. sST2 was suggested as a factor in the pathogenesis of COPD and emerged as a predictor of mortality in other non-communicable diseases. The role of sST2 as a predictor of mortality remains unclear in COPD yet. In this cohort study, we measured circulating concentrations of IL-33 and sST2 in the serum of patients with stable COPD (n = 59), patients with acute exacerbation of COPD (n = 29) and smoking (n = 20) and non-smoking controls (n = 20), using commercially available ELISAs, and investigated the prognostic role of sST2 in stable COPD. sST2 levels were significantly higher in COPD patients and smokers compared with non-smoking controls. We identified systolic blood pressure, forced expiratory volume in 1 s (FEV1% predicted), neutrophil count, lactate dehydrogenase and pack-years index as independent predictors of sST2 levels. During a median follow-up time of 10.6 years, 28 patients (47.5%) died. sST2 was an independent predictor of all-cause mortality in patients with COPD with a hazard ratio of 2.9 (95% CI 1.1–8.4, p = 0.035) per one standard deviation after adjustment for age, sex, pack-years, FEV1% predicted and C-reactive protein (CRP). sST2 concentrations are associated with severity of disease and long-term outcome in patients with COPD.

Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs. It causes symptoms such as breathlessness, cough, and production of phlegm. In people with COPD, these symptoms often reduce the quality of their lives. From time to time, symptoms may get worse in people with the disease. This worsening is known as ‘exacerbation’. Exacerbations of COPD can be so bad that they lead to hospital admissions. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) regularly gives advice to doctors around the world. This can help them to provide their patients with the best possible treatment for COPD. However, people with the disease and healthcare systems vary from country to country. This means that the guidance may need to be adjusted to the needs and available resources of different regions. This review looks at how COPD is treated in Central and Eastern Europe. We suggest how to adapt the GOLD recommendations to best suit the Central and Eastern European region. Graphical Abstract

Patients with lung cancer frequently suffer from physical deconditioning, low exercise capacity, and reduced quality of life. There is little evidence on the effects of a structured outpatient pulmonary rehabilitation program (OPR) on exercise capacity and symptom load in these patients. We performed a retrospective, single-center analysis of surgically resected lung cancer patients, who underwent a multiprofessional 6-week OPR. The primary endpoint was a change in the six-minute walk test distance (6 MWT). Secondary endpoints included changes in maximal workload and constant work-rate test results during cycle-ergometry, upper and lower extremity strength, and inspiratory muscle strength. The COPD Assessment Test (CAT) was used to assess symptom burden. Fifty-seven patients were included. Of those, fifty-two (91.2%) completed the full 6 weeks of OPR. The mean age was 56.4 (SD 9.2) years, and 58% were female. At completion of OPR, there was a statistically significant mean of a 50 m (95% CI, 29.6–70.7; p < 0.001) increase in 6 MWT. Significant improvements were also seen in all other exercise and strength tests (p < 0.001), accompanied by a significant reduction in the CAT score (mean difference −3.1, p = 0.001). No adverse effects were reported. OPR for surgically resected lung cancer patients was safe and effective and showed high adherence in the current study.

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24–45). The response rate in treatment-naïve patients was 27% (95% CI, 8–58). The median progression-free and overall survival was 5 months (95% CI, 3.5–6.5) and 12 months (95% CI, 6.8–17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.