Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma.

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) have adverse outcomes. We evaluated the efficacy and safety of the phosphatidylinositol 3-kinase inhibitor copanlisib in patients with relapsed/refractory DLBCL and assessed the relationship between efficacy and DLBCL cell of origin (COO; activated B-cell like [ABC] and germinal center B-cell like [GCB]) and other biomarkers. The primary endpoint was objective response rate (ORR) in DLBCL COO subgroups (ABC, GCB, and unclassifiable) and by CD79B mutational status (NCT02391116). Sixty-seven patients received copanlisib (ABC DLBCL, n = 19; GCB DLBCL, n = 30; unclassifiable, n = 3; missing, n = 15). The ORR was 19.4%; 31.6% and 13.3% in ABC and GCB DLBCL patients, respectively. ORR was 22.2%/20.0% for patients with/without CD79B mutations (wild type, n = 45; mutant, n = 9; missing, n = 13). Overall median progression-free survival and duration of response were 1.8 and 4.3 months, respectively. Adverse events included hypertension (40.3%), diarrhea (37.3%), and hyperglycemia (32.8%). Aberrations were detected in 338 genes, including BCL2 (53.7%) and MLL2 (53.7%). A 16-gene signature separating responders from nonresponders was identified. Copanlisib treatment demonstrated a manageable safety profile in patients with relapsed/refractory DLBCL and a numerically higher response rate in ABC vs. GCB DLBCL patients.

Randomized phase II study of dacomitinib (PF-00299804), an irreversible pan-human epidermal growth factor receptor inhibitor, versus erlotinib in patients with advanced non-small-cell lung cancer.

PURPOSE: This randomized, open-label trial compared dacomitinib (PF-00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, with erlotinib, a reversible EGFR inhibitor, in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, no prior HER-directed therapy, and one/two prior chemotherapy regimens received dacomitinib 45 mg or erlotinib 150 mg once daily. RESULTS: One hundred eighty-eight patients were randomly assigned. Treatment arms were balanced for most clinical and molecular characteristics. Median progression-free survival (PFS; primary end point) was 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (hazard ratio [HR] = 0.66; 95% CI, 0.47 to 0.91; two-sided P = .012); in patients with KRAS wild-type tumors, median PFS was 3.71 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR = 0.55; 95% CI, 0.35 to 0.85; two-sided P = .006); and in patients with KRAS wild-type/EGFR wild-type tumors, median PFS was 2.21 months for patients treated with dacomitinib and 1.84 months for patients treated with erlotinib (HR = 0.61; 95% CI, 0.37 to 0.99; two-sided P = .043). Median overall survival was 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR = 0.80; 95% CI, 0.56 to 1.13; two-sided P = .205). Adverse event-related discontinuations were uncommon in both arms. Common treatment-related adverse events were dermatologic and gastrointestinal, predominantly grade 1 to 2, and more frequent with dacomitinib. CONCLUSION: Dacomitinib demonstrated significantly improved PFS versus erlotinib, with acceptable toxicity. PFS benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants.

A survey of the perspectives of patients who are seriously ill regarding end-of-life decisions in some medical institutions of Korea, China and Japan.

PURPOSE: The debate about the end-of-life care decision is becoming a serious ethical and legal concern in the Far-Eastern countries of Korea, China and Japan. However, the issues regarding end-of-life care will reflect the cultural background, current medical practices and socioeconomic conditions of the countries, which are different from Western countries and between each other. Understanding the genuine thoughts of patients who are critically ill is the first step in confronting the issues, and a comparative descriptive study of these perspectives was conducted by collaboration between researchers in all three countries. METHODS: Surveys using self-reporting paper questionnaire forms were conducted from December 2008 to April 2009 in Korea (six hospitals in two regions), China (five hospitals in four regions) and Japan (nine hospitals in one region). The subjects were patients who were critically ill who had been diagnosed as having cancer. A total of 235 participants (Korea, 91; China, 62; Japan, 52) were eventually recruited and statistically analysed. RESULTS: Most respondents had sometimes or often thought of their own death, mostly fear of 'separation from loved ones'. They wanted to hear the news regarding their own condition directly and frankly from the physician. A quarter of them preferred making end-of-life care decisions by themselves, while many respondents favoured a 'joint decision' with their family members. The most favoured proxy decision maker was the spouse, followed by the children. Most admitted the necessity of 'advance directives' and agreed with artificial ventilation withdrawal in irreversible conditions. The most common reason was 'artificial prolongation of life is unnecessary'. Most respondents agreed with the concept of active euthanasia; however, significant differences were sometimes observed in the responses according to variables such as patient's country of origin, age, gender and education level. CONCLUSION: Patients in Far-Eastern countries gave various responses regarding end-of-life care decisions. Although familial input is still influential, most patients think of themselves as the major decision maker and accept the necessity of advance directives with Westernization of the society. Artificial ventilation withdrawal and even active euthanasia may be acceptable to them.

Biological characteristics and treatment outcomes of metastatic or recurrent neuroendocrine tumors: tumor grade and metastatic site are important for treatment strategy.

BACKGROUND: Studies about the biology, treatment pattern, and treatment outcome of metastatic/recurrent neuroendocrine tumor (NET) have been few. METHODS: We enrolled patients with metastatic/recurrent NET diagnosed between January 1996 and July 2007 and retrospectively analyzed. RESULTS: A total of 103 patients were evaluated. Twenty-six patients (25.2%) had pancreatic NET, 27 (26.2%) had gastrointestinal NET, 2 (1.9%) had lung NET, 28 (27.2%) had NET from other sites, and 20 (19.4%) had NET from unknown origin. The liver was the most common metastatic site (68.9%). Thirty-four patients had grade 1 disease, 1 (1.0%) had grade 2 disease, 15 (14.6%) had grade 3 disease, 9 (8.7%) had large cell disease, and 7 (6.8%) had small cell disease.Sixty-six patients received systemic treatment (interferon, somatostatin analogues or chemotherapy), 64 patients received local treatment (TACE, radiofrequency ablation, metastasectomy, etc.). Thirty-six patients received both systemic and local treatments.Median overall survival (OS) was 29.0 months (95% confidence interval, 25.0-33.0) in the 103 patients. OS was significantly influenced by grade (p = .001). OS was 43.0, 23.0, and 29.0 months in patients who received local treatment only, systemic treatment only, and both treatments, respectively (p = .245). The median time-to-progression (TTP) was 6.0 months. Overall response rate was 34.0% and disease-control rate was 64.2%. TTP was influenced by the presence of liver metastasis (p = .011). CONCLUSIONS: OS of metastatic/recurrent NET was different according to tumor grade. TTP was different according to metastasis site. Therefore, development of optimal treatment strategy based on the characteristics of NET is warranted.

Validation study of the Korean version of the McGill Quality of Life Questionnaire.

This study aimed to test the reliability and validity of the Korean version of McGill Quality of Life Questionnaire (MQOL-K) for use with 140 palliative care patients in Korea. Our results confirmed the suitability of using the 16 questions of the questionnaire clustered into four domains (physical, psychological, existential and support) as in the original version of the MQOL, although the distribution of items among the domains differed somewhat from the original. The MQOL-K demonstrated moderate to high internal consistency (Cronbach's alpha, 0.62-0.90), convergent validity without scaling error, and a good concurrent validity with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, sense of dignity, and general health perception. In addition, we tested the clinical validity of the MQOL-K using a known group comparison to quantify sensitivity. Regression results indicated that the existential and psychological domains had independent effects on the overall quality of life of patients in Korea. Therefore, the MQOL-K is deemed suitable for assessing the quality of life in a Korean palliative care setting.