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Purpose An increasing number of advanced non–small cell lung cancer (NSCLC) cases are being reported in the ageing population. However, studies on the use of afatinib in elderly patients are scarce. We conducted a prospective multicentre, single-arm, and open-label phase II trial for low-dose afatinib (30 mg/day) use in elderly patients with NSCLC with EGFR mutation to assess quality-of-life (QOL) and pharmacokinetic (PK)/pharmacogenomic (PGx) parameters. Patients and methods The primary end-point was the objective response rate (ORR), and the planned number of registered cases was 35, with a threshold ORR of 50%, an expected ORR of 75%, α of 0.05, and β of 0.1. Secondary end-points were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (Css) and at the occurrence of clinically significant AEs. Results The median age of the patients was 79 years. The ORR was 80.0% and the disease control rate was 91.4%. The median PFS and OS were 15.6 and 29.5 months, respectively. Four patients discontinued because of AEs. Treatment-related death was not observed. No significant change in QOL was observed at baseline and after 4, 8, and 12 weeks. Css was comparable with those in previous reports and was significantly higher in patients with grade 3 AEs. Direct correlations between afatinib treatment and PGx profiles were not observed. Conclusions An afatinib starting dose of 30 mg/day could be an effective and safe treatment option for elderly patients.

The immune checkpoint inhibitor nivolumab is entering routine oncologic practice. We investigated the safety and efficacy of nivolumab in the real world and alternative predictive factors for survival in patients with advanced non-small-cell lung cancer (NSCLC).We performed a prospective observational study to evaluate the activity of nivolumab treatment for chemotherapy-refractory NSCLC. Patients were treated with nivolumab once every 2 weeks, and the efficacy was assessed every 8 ± 2 weeks.Fifty-two patients were enrolled after nivolumab approval in Japan. These patients received a median of 4 (range, 1-43) cycles of nivolumab. Overall objective response was observed in 12 patients (23.1%). Median progression-free survival was 2.1 (95% confidence interval, 1.0-3.2) months, and 1-year overall survival rate was 59.9%. A total of 23 immune-related adverse events occurred in 20 patients, as follows: 7 cases of pneumonitis, 6 of oral mucositis, 5 of hypothyroidism, 2 of colitis, 2 of liver dysfunction, and 1 of arthritis. All patients recovered after appropriate management. A pretreatment neutrophil-to-lymphocyte ratio (NLR) of ≥ 5 was significantly associated with poor prognosis compared to NLR 5 (hazard ratio, 4.52; 95% confidence interval, 1.84-11.14; P = .013), independently.Nivolumab showed promising activity with a manageable safety profile in clinical practice, consistent with effects of previous clinical trials. This drug could affect a specific population of patients with advanced NSCLC, and pretreatment NLR was a candidate for surrogate markers for survival benefit of patients with NSCLC treated with nivolumab.

Background: Hospital with long-term treatment ward well intermediates between specialized medical care and home medical care, and also plays an important role in the end of life care of lung cancer. We examined its prospects from the viewpoint of functional changes of various wards with the revision of medical treatment fees for 2014. Methods: We investigated medical records of 73 lung cancer patients (48males, 25females, median age 77) treated in Tokyo Kensei Hospital and already dead since 2008 in that year we opened long-term treatment ward. We checked frequency and period of hospitalization, involvement with long-term treatment ward, and situation of medical cooperation included home medical care. Results: 3cases are in Stage2, 11cases in Stage3, 57cases in Stage4, 2cases in unknown Stage, and patients 75 years or older exceeded 60%. 43cases entered hospital only once, and 24cases passed away in long-term treatment ward, 5cases at home. In those cases we had frequent contact with various hospitals and clinics. Average hospitalization period was 34days, and 41patients entered long-term treatment ward, whose mean days in hospital were 58, significantly longer than those of other patients. 4cases entered hospital 10times or more, received repeated chemotherapy in general ward, and 2cases of them entered long-term treatment ward in their end of life care. Conclusions: In medical care of aged patients with lung cancer, hospital with long-term treatment ward is important from the viewpoint of medical cooperation. Especially in the trend of medical shift towards home care, we should consider the backgrounds of the patients and their families, and estimate the hospitalization period. Finally we should selectively use various wards effectively, for example sub-acute medical ward expected as the ward based on the region in the near future.

Aim: Repetitive genotyping is useful to assess the genetic evolution of NSCLC during the treatment course, but the need for a biopsy is a major barrier. Digital PCR is a promising procedure for the detection of mutant alleles in the plasma of cancer patients. Methods: This prospective study enrolled patients with NSCLC harboring known EGFR mutations and who had experienced disease progression during ongoing EGFR-TKI therapy. Eligible patients received daily gefitinib (250 mg) and either PEM (500 mg/m2) or S-1 (80 mg/m2, day 1-14). The treatment was repeated every 3 weeks until disease progression or unacceptable toxicity. Plasma was collected before and after the combination therapy, and digital PCR was performed to assess EGFR L858R, exon 19 deletions and T790M. Serum hepatocyte growth factor (HGF) was measured along with tumor evaluation. Results: From May 2012 to January 2014, nine patients were enrolled. Median age was 67 (range, 52-80) years, and seven patients were female. EGFR mutations at the time of disease diagnosis included L858R in six patients and exon 19 deletions in three patients. Patterns of disease progression during adjacent EGFR-TKI therapy were acquired resistance in seven patients, and primary resistance in two patients. Known EGFR mutations were detected in plasma samples from six (67%) patients at study enrollment. Of these, T790M was concurrently detected in three (50%) patients. HGF level was elevated in one patient with T790M mutation. Four patients underwent gefitinib plus PEM therapy, and five patients received treatment with gefitinib and S-1. The median number of cycles delivered was five, and the median progression-free survival was 5.8 months. Efficacy outcomes did not differ between the two treatment regimens. After the combination therapy, plasma T790M status changed to positive in two patients. HGF did not increase in any patient. Conclusions: Data from noninvasive genetic profiling suggest that the retention of the T790M-positive cell population contributed to the better outcomes in response to combination therapy with EGFR-TKI and cytotoxic agents. Disclosure: A. Kagei: The author is an employee of GeneticLab Co., Ltd. (Sapporo, Japan); T. Yamamoto: The author is an employee of GeneticLab Co., Ltd. (Sapporo, Japan). All other authors have declared no conflicts of interest.

Background Eligibility is often narrowed in clinical trials of targeted drugs because of specific adverse effects. Modified eligibility criteria can affect endpoints such as overall survival independently of the actual effect of an investigational drug. Methods Patients with stage IIIB/IV, non-squamous non-small cell lung cancer (NSCLC) who started chemotherapy from 2005 to 2009 were reviewed. Bevacizumab (BV) was first used to treat lung cancer at our institution in 2010. We divided patients into BV-eligible (A) and -ineligible (B) groups. To estimate survival, Kaplan-Meier curves were calculated and compared between the groups using the log-rank test. We also examined the prognostic impact of age, gender, M factor, performance status (PS), use of platinum in first-line chemotherapy, history of hemoptysis, major blood vessel invasion (MVI) by the tumor and clinically significant cardiovascular disease upon overall survival using the Cox proportional hazards model. A radiologist who was blinded to the clinical outcomes evaluated MVI. All tests were two sided with a significance level of 0.05. Results Among 576 patients with lung cancer who undergone chemotherapy at our department, 283 of them had stage IIIB/IV non-squamous NSCLC. After excluding 15 patients with indications for combined chemoradiotherapy and 22 with PS 3/4, the eligibility of 246 patients for BV was finally evaluated. Eighty-nine patients were considered ineligible for BV (cohort B), based on one or more of a history of hemoptysis (N = 32), MVI (N = 64) and cardiovascular disease (N = 13). Eligibility could not be determined in ten patients and the remaining 147 patients were classified into cohort A. Overall survival was significantly better in cohort A (median, 14.9 months) than in cohort B (median, 8.6 months; hazard ratio, 0.55; 95%CI, 0.42-0.74; P Conclusion Eligibility for BV itself is a powerful prognostic factor for patients with non-squamous NSCLC. Disclosure All authors have declared no conflicts of interest.

Background Thymic carcinoma is a rare cancer that represents an incidence of 0.15 per 100,000 persons per year. Thus, clinical characteristics and prognostic factors have not been investigated in detail. In this study, we tried to elucidate the disease profiles, outcomes, and prognostic factors for survival among patients with advanced thymic carcinoma treated with palliative-intent chemotherapy. Patients and methods This study was a retrospective review of medical records of 38 patients treated with palliative-intent chemotherapy for advanced thymic carcinoma between 1991 and 2011. Clinical demographics, histology, overall survival, and factors expected to predict survival were analyzed. Differences in survival were assessed using Kaplan-Meier analysis and uni- and multivariate Cox proportional hazards regression analyses. Results The study included 20 males (52.6%) and 18 females (47.4%). The median age at diagnosis was 59.5 years. The most common metastatic sites at diagnosis were lung (44.7%), liver (15.8%), lymph nodes (15.8%), bone (13.2%), and brain (5.7%). The most common histological subtypes were squamous cell carcinoma (73.7%), followed by neuroendocrine carcinoma (15.8%), and mucoepidermoid carcinoma (7.9%). The median survival time was 25.4 months. Overall survival rates at 1- and 2-years were 73.6% and 52.6%, respectively. In univariate and multivariate analyses, the only favorable prognostic factor for overall survival was response to first-line chemotherapy (p = 0.009). Conclusion Response to first-line chemotherapy may be a prognostic factor for overall survival in patients with advanced thymic carcinoma. Disclosure All authors have declared no conflicts of interest.