11 research outputs found
A randomized, double-blind study of zinpentraxin alfa in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib:stage 2 of a phase II trial
A randomized, double-blind study of zinpentraxin alfa in patients with myelofibrosis who were previously treated with or ineligible for ruxolitinib:stage 2 of a phase II trial
Application of a real world endpoint to identify and characterize genetic profiles of patients (pts) with poor prognosis in advanced non-small-cell lung cancer (aNSCLC).
Whole Exome Sequencing of CLL Before Second-Line Treatment with Fludarabine and Cyclophosphamide with or without Rituximab (REACH trial).
A noninterventional, multinational study to assess PD-L1 expression in cytological and histological lung cancer specimens
BACKGROUND: The diagnosis of advanced lung cancer is made with minimally invasive procedures. This often results in the availability of cytological material only for subtype determination and companion diagnostic testing, with the latter being technically and clinically validated on histological material only. Thus, the primary objective of the MO29978 clinical study was to assess programmed death ligand 1 (PD-L1) protein expression on cytology samples as surrogates for histology samples in patients with lung cancer. METHODS: Formalin-fixed, paraffin-embedded histological samples and cytological cell blocks from 190 patients were analyzed with immunohistochemical assays using the rabbit monoclonal anti-PD-L1 antibody clones SP142 and SP263. PD-L1 expression was quantified on both tumor cells (TC) and tumor-infiltrating immune cells (IC). Overall concordance, sensitivity, specificity, and accuracy, with a 1% cutoff used for both assays, were assessed for PD-L1 expression on TC and IC. RESULTS: In non-small cell lung cancer histology and cytology samples measured with the PD-L1 (SP142) antibody (n = 173), the intraclass correlation coefficients were 0.40 and 0.06 on TC and IC, respectively. With SP142 and SP263, accuracies of 74.1% for TC and 51.9% for IC and accuracies of 75.2% for TC and 61.2% for IC, respectively, were reported. CONCLUSIONS: Overall, this study has demonstrated that PD-L1 analysis on TC is feasible in cytological material, but quantification is challenging. Tumor tissue should be preferred over cell block cytology for PD-L1 immunohistochemical analysis unless laboratories have validated their cytology preanalytical approaches and demonstrated the comparability of histology and cytology for TC PD-L1 results
Safety and efficacy of zinpentraxin alfa as monotherapy or in combination with ruxolitinib in myelofibrosis:stage I of a phase II trial
Prognostic value of MRD in CLL patients with comorbidities receiving chlorambucil plus obinutuzumab or rituximab
Pharmacodynamic Effects and Mechanisms of Resistance to Vemurafenib in Patients With Metastatic Melanoma
Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): extended follow-up of a phase 3, randomised, open-label study
BACKGROUND: In the BRIM-3 trial, vemurafenib was associated with risk reduction versus dacarbazine of both death and progression in patients with advanced BRAF(V600) mutation-positive melanoma. We present an extended follow-up analysis of the total population and in the BRAF(V600E) and BRAF(V600K) mutation subgroups.
METHODS: Patients older than 18 years, with treatment-naive metastatic melanoma and whose tumour tissue was positive for BRAF(V600) mutations were eligible. Patients also had to have a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate haematological, hepatic, and renal function. Patients were randomly assigned by interactive voice recognition system to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg/m(2) of body surface area intravenously every 3 weeks). Coprimary endpoints were overall survival and progression-free survival, analysed in the intention-to-treat population (n=675), with data censored at crossover. A sensitivity analysis was done. This trial is registered with ClinicalTrials.gov, NCT01006980.
FINDINGS: 675 eligible patients were enrolled from 104 centres in 12 countries between Jan 4, 2010, and Dec 16, 2010. 337 patients were randomly assigned to receive vemurafenib and 338 to receive dacarbazine. Median follow-up was 12路5 months (IQR 7路7-16路0) on vemurafenib and 9路5 months (3路1-14路7) on dacarbazine. 83 (25%) of the 338 patients initially randomly assigned to dacarbazine crossed over from dacarbazine to vemurafenib. Median overall survival was significantly longer in the vemurafenib group than in the dacarbazine group (13路6 months [95% CI 12路0-15路2] vs 9路7 months [7路9-12路8]; hazard ratio [HR] 0路70 [95% CI 0路57-0路87]; p=0路0008), as was median progression-free survival (6路9 months [95% CI 6路1-7路0] vs 1路6 months [1路6-2路1]; HR 0路38 [95% CI 0路32-0路46]; p<0路0001). For the 598 (91%) patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13路3 months (95% CI 11路9-14路9) compared with 10路0 months (8路0-14路0) in the dacarbazine group (HR 0路75 [95% CI 0路60-0路93]; p=0路0085); median progression-free survival was 6路9 months (95% CI 6路2-7路0) and 1路6 months (1路6-2路1), respectively (HR 0路39 [95% CI 0路33-0路47]; p<0路0001). For the 57 (9%) patients with BRAF(V600K) disease, median overall survival in the vemurafenib group was 14路5 months (95% CI 11路2-not estimable) compared with 7路6 months (6路1-16路6) in the dacarbazine group (HR 0路43 [95% CI 0路21-0路90]; p=0路024); median progression-free survival was 5路9 months (95% CI 4路4-9路0) and 1路7 months (1路4-2路9), respectively (HR 0路30 [95% CI 0路16-0路56]; p<0路0001). The most frequent grade 3-4 events were cutaneous squamous-cell carcinoma (65 [19%] of 337 patients) and keratoacanthomas (34 [10%]), rash (30 [9%]), and abnormal liver function tests (38 [11%]) in the vemurafenib group and neutropenia (26 [9%] of 287 patients) in the dacarbazine group. Eight (2%) patients in the vemurafenib group and seven (2%) in the dacarbazine group had grade 5 events.
INTERPRETATION: Inhibition of BRAF with vemurafenib improves survival in patients with the most common BRAF(V600E) mutation and in patients with the less common BRAF(V600K) mutation.
FUNDING: F Hoffmann-La Roche-Genentech