Concordance Between Tissue ALK Detection by Immunohistochemistry and Plasma ALK Detection by Next-Generation Sequencing in the Randomized Phase 3 ALEX Study in Patients With Treatment-Naive Advanced ALK-Positive NSCLC

INTRODUCTION: The Blood First Assay Screening Trial revealed the clinical applicability of blood-based next-generation sequencing to identify patients with ALK-positive NSCLC for alectinib treatment. To understand the relationship between tissue-based versus blood-based testing, we retrospectively investigated concordance between VENTANA ALK (D5F3) CDx immunohistochemistry and the FoundationACT (FACT; Foundation Medicine, Inc.) plasma assay, and compared clinical efficacy between phase 3 ALEX study subpopulations. METHODS: Patients with advanced ALK-positive (by immunohistochemistry) NSCLC were randomized 1:1 to alectinib 600 mg or crizotinib 250 mg, twice daily. Assessable baseline plasma samples were analyzed for ALK positivity by FACT; positive percent agreement with immunohistochemistry was evaluated. Progression-free survival (PFS), duration of response, and objective response rate were compared between intention-to-treat (ITT) and biomarker-evaluable populations, and plasma ALK-positive and plasma ALK-negative subpopulations. RESULTS: In the ITT population (303 patients; alectinib, 152; crizotinib, 151), all patients had ALK-positive tumors by immunohistochemistry. In the biomarker-evaluable population (149 patients; alectinib, 76; crizotinib, 73), 105 had plasma ALK-positive and 44 had plasma ALK-negative tumors. Positive percent agreement between immunohistochemistry and FACT was 70.5% (105 of 149; 95% confidence interval: 62.5-77.7). Baseline characteristics were generally balanced, with some exceptions, notably tumor burden. Median PFS in plasma ALK-positive and ALK-negative patients was 22.4 months and not estimable with alectinib and 7.3 months and 12.9 months with crizotinib, respectively; median duration of response was 25.9 months and not estimable with alectinib and 5.6 months and 11.5 months with crizotinib, respectively. CONCLUSIONS: Reasonable concordance between FACT and immunohistochemistry was observed; both methods are valuable in identifying ALK-positive patients, separately or concurrently. Alectinib was found to have superior PFS in the plasma ALK-positive population, as in the ITT population

Nursing care for patient with Crohn's disease in the surgical department

U radu se prikazuje vanjskotrgovinska razmjena Republike Hrvatske od 2012. do 2016. godine. Glavne komponente vanjskotrgovinske razmjene su, izvoz i uvoz, a njihov odnos iskazuje se na vanjskotrgovinskoj bilanci, u pozitivnom iznosu kao suficit, u negativnom kao deficit. Rad prikazuje kretanje izvoza i uvoza u apsolutnim iznosima i strukturu vanjskotrgovinske bilance te daje pregled vanjskotrgovinske razmjene s najvažnijim zemljama partnerima Republike Hrvatske. Činjenica je da sve zemlje teže ostvarivanju suficita, stoga se u radu naglašava važnost i mogućnosti stimuliranja izvoza u Republici Hrvatskoj. Metodom intervjua, na primjeru iz prakse jednog izvoznika, prikazani su problemi s kojima se susreće u poslovanju.This thesis discusses foreign trade in the Republic of Croatia since 2012 until 2016. Relations in the foreign trade are determined by Croatia's foreign trade policy. Key foreign trade components have been defined, as well as import and export. Their relations are shown in the foreign trade balance, in the positive amount as surplus and in the negative as deficit. This thesis shows the movement of exports and imports in absolute terms and structure of foreign trade balance and it gives an overview of foreign trade with the most important Croatia's partner countries. It is a fact that all countries seek to achieve a surplus, therefore, the importance and the possibility of export stimulation has been emphasized. This paper shows, in an interview, all the problems that a Croatian exporter has had during his business experience

Development of a functional screening in melanocytes

SIGLEAvailable from British Library Document Supply Centre- DSC:DXN059641 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Comparative effectiveness from a single-arm trial and real-world data: alectinib versus ceritinib.

To compare the overall survival of anaplastic lymphoma kinase-positive non-small-cell lung cancer patients who received alectinib with those who received ceritinib.Two treatment arms (alectinib [n = 183] and ceritinib [n = 67]) were extracted from clinical trials and an electronic health record database, respectively. Propensity scores were applied to balance baseline characteristics. Kaplan-Meier and multivariate Cox regression were conducted.After propensity score adjustment, baseline characteristics were balanced. Alectinib had a prolonged median overall survival (alectinib = 24.3 months and ceritinib = 15.6 months) and lower risk of death (hazard ratio: 0.65; 95% CI: 0.48-0.88).Alectinib was associated with prolonged overall survival versus ceritinib, which is consistent with efficacy evidence from clinical trials

Patient-reported outcomes in a phase II, North American study of alectinib in patients with ALK-positive, crizotinib-resistant, non-small cell lung cancer.

BackgroundIn a phase II North American study (NP28761; NCT01871805), the anaplastic lymphoma kinase (ALK) inhibitor alectinib demonstrated both systemic and central nervous system (CNS) efficacy with good tolerability in patients with ALK-positive non-small cell lung cancer. We describe patient-reported outcomes (PROs) from the NP28761 study.Patients and methodsPROs and health-related quality of life (HRQoL) benefits were assessed using two self-administered questionnaires (the European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire-Core (EORTC QLQ-C30), and the 13-item EORTC QLQ-lung cancer-specific module) at enrolment and every 6 weeks until week 66, disease progression or death.ResultsClinically meaningful mean improvements (≥10 point change from baseline) were observed in 10 domains, including global health status (GHS), role and social functioning, fatigue, pain, dyspnoea, and appetite loss. A clinically meaningful improvement was observed in GHS from the first assessment (6 weeks) until week 60. Alectinib demonstrated a rapid effect, with a median time to symptom improvement, using the composite endpoint of cough, dyspnoea and pain in the chest, of 1.4 months (6.1 weeks) (95% CI 1.4 to 1.6) and a median time to symptom deterioration of 5.1 months (22.1 weeks) (95% CI 2.8 to 6.8). Patients with CNS metastases at baseline experienced comparable HRQoL over the duration of the study as patients without CNS metastases. Exploratory analysis showed that the occurrence of an objective response may be associated with a better HRQoL.ConclusionsPatients treated with alectinib in this phase II study achieved clinically meaningful improvements in HRQoL and symptoms and had delayed time to symptom deterioration

Alectinib in crizotinib-refractory alk-rearranged non-small-cell lung cancer: A phase II global study

Purpose Crizotinib confers improved progression-free survival compared with chemotherapy in anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC), but progression invariably occurs. We investigated the efficacy and safety of alectinib, a potent and selective ALK inhibitor with excellent CNS penetration, in patients with crizotinib-refractory ALK-positive NSCLC. Patients and Methods Alectinib 600 mg was administered orally twice daily. The primary end point was objective response rate (ORR) by central independent review committee (IRC). Results Of the 138 patients treated, 84 patients (61%) had CNS metastases at baseline, and 122 were response evaluable (RE) by IRC. ORR by IRC was 50%(95% CI, 41% to 59%), and the median duration of response (DOR) was 11.2 months (95% CI, 9.6 months to not reached). In 96 patients (79%) previously treated with chemotherapy, the ORR was 45% (95% CI, 35% to 55%). Median IRC-assessed progression-free survival for all 138 patients was 8.9 months (95% CI, 5.6 to 11.3 months). CNS disease control rate was 83% (95% CI, 74% to 91%), and the median CNS DOR was 10.3 months (95% CI, 7.6 to 11.2 months). CNS ORR in 35 patients with baseline measurable CNS lesions was 57% (95% CI, 39% to 74%). Of the 23 patients with baseline CNS metastases (measurable or nonmeasurable) and no prior radiation, 10 (43%) had a complete CNS response. At 12 months, the cumulative CNS progression rate (24.8%) was lower than the cumulative non-CNS progression rate (33.2%) for all patients. Common adverse events were constipation (33%), fatigue (26%), and peripheral edema (25%); most were grade 1 to 2. Conclusion Alectinib is highly active and well tolerated in patients with advanced, crizotinib-refractory ALK-positive NSCLC, including those with CNS metastases. (C) 2015 by American Society of Clinical Oncology