Hirohisa Ichikawa

Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non–Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)

Based on our preclinical study results, which showed that the activation of the hepatocyte growth factor/MET pathway is a potential mechanism of acquired resistance to alectinib, we launched the ALRIGHT (OLCSG1405 [alectinib-refractory non-small-cell lung cancer patients harboring the EML4-ALK fusion gene]), a phase II trial of the anaplastic lymphoma kinase (ALK)/MET inhibitor crizotinib in patients with non-small-cell lung cancer refractory to alectinib and harboring the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion gene. Patients with ALK-rearranged tumors who have developed disease progression during alectinib treatment will receive crizotinib monotherapy until disease progression or the occurrence of unacceptable toxicity. The primary endpoint is set as the objective response rate, assuming that a response in 50% of eligible patients will indicate potential usefulness and that 15% would be the lower limit of interest (1-sided α of 0.05, β of 0.20). The estimated accrual number of patients is 9. The secondary endpoints include progression-free survival, overall survival, adverse events, and patient-reported outcomes. We will also take tissue samples before crizotinib monotherapy to conduct an exploratory analysis of ALK and hepatocyte growth factor/MET expression levels and gene alterations (eg, mutations, amplifications, and translocations). We will obtain information regarding whether crizotinib, which targets not only ALK, but also MET, can truly produce efficacy with acceptable safety profiles in ALK+ non-small-cell lung cancer even in the alectinib-refractory setting.

Long-term effects of beta-blocker use on lung function in Japanese patients with chronic obstructive pulmonary disease

Background Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD) is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. Patients and methods We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1) was assessed. Results At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years); 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD) stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC), FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (−7.6±93.5 mL/year vs −4.7±118.9 mL/year, P=0.671). After controlling for relevant confounders in multivariate analyses, it was found that beta-blocker use was not significantly associated with the annual decline in FEV1 (β=−0.019; 95% confidence interval: −0.073 to 0.036; P=0.503). Conclusion Long-term beta-blocker use in Japanese COPD patients might not affect the FEV1, one of the most important parameters of lung function in COPD patients.

Phase II Study of the EGFR-TKI Rechallenge With Afatinib in Patients With Advanced NSCLC Harboring Sensitive EGFR Mutation Without T790M: Okayama Lung Cancer Study Group Trial OLCSG 1403

Abstract Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first‐line therapy for patients with EGFR‐mutated non–small‐cell lung cancer (NSCLC) have shown a significantly better objective response rate and progression‐free survival than platinum doublet therapy. However, acquired resistance often occurs within 12 months. One of the potential strategies for treating acquired resistance in NSCLC is the readministration of EGFR‐TKIs, a strategy that has mainly been evaluated using gefitinib or erlotinib. The aim of the present study is to investigate the efficacy and safety of EGFR‐TKI readministration with afatinib in patients with advanced NSCLC harboring activating EGFR mutations without T790M. The primary endpoint is progression‐free survival. The secondary endpoints include the objective response rate, disease control rate, overall survival, toxicity, and quality of life. A total of 12 patients will be enrolled in this trial.

Relationship of locomotive syndrome with health-related quality of life among patients with obstructive sleep apnea syndrome

[Purpose] This study aimed to examine the prevalence of locomotive syndrome among patients with obstructive sleep apnea syndrome (OSAS) using the “loco-check” recently developed by the Japanese Orthopedic Association, and to compare health-related quality of life (HRQOL) among patients with and without locomotive syndrome. [Subjects and Methods] This cross-sectional study evaluated 1,195 outpatients with OSAS (1,030 males and 165 females). Locomotive syndrome was evaluated using the Japanese Orthopedic Association’s “loco-check”. HRQOL and psychological distress were evaluated using the EuroQol 5-dimensional (EQ-5D) and 6-item Kessler questionnaires. [Results] Locomotive syndrome was detected in 578 patients (48.4%), including 398 males (38.6% of males) and 119 females (70.3% of females). Patients with OSAS and locomotive syndrome had significantly lower EQ-5D scores, compared to patients without locomotive syndrome. Multiple regression analysis revealed that HRQOL among patients with OSAS was independently associated with locomotive syndrome, age, gender, body mass index, apnea hypopnea index, the Japanese version of the Epworth Sleepiness Scale score, and exercise habits. [Conclusion] The prevalence of locomotive syndrome was thought to be comparatively high in patients with OSAS, and locomotive syndrome was associated with lower HRQOL, even after adjusting for confounding factors. Prevention or management of locomotive syndrome may be beneficial for improving HRQOL among patients with OSAS.