36 research outputs found
First‐line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive non‐squamous non‐small cell lung cancer
Background Epidermal growth factor receptor (EGFR) mutation positive (M+) non‐small cell lung cancer (NSCLC) is emerging as an important subtype of lung cancer comprising 10% to 15% of non‐squamous tumours. This subtype is more common in women than men and is less associated with smoking. Objectives To assess the clinical effectiveness of single ‐agent or combination EGFR therapies used in the first‐line treatment of people with locally advanced or metastatic EGFR M+ NSCLC compared with other cytotoxic chemotherapy (CTX) agents used alone or in combination, or best supportive care (BSC). The primary outcome was overall survival. Secondary outcomes included progression‐free survival, response rate, toxicity, and quality of life. Search methods We conducted electronic searches of the the Cochrane Register of Controlled Trials (CENTRAL) (2015, Issue 6), MEDLINE (1946 to 1 June 2015), EMBASE (1980 to 1 June 2015), and ISI Web of Science (1899 to 1 June 2015). We also searched the conference abstracts of the American Society for Clinical Oncology and the European Society for Medical Oncology (1 June 2015); Evidence Review Group submissions to the National Institute for Health and Care Excellence; and the reference lists of retrieved articles. Selection criteria Parallel randomised controlled trials comparing EGFR‐targeted agents (alone or in combination with cytotoxic agents or BSC) with cytotoxic chemotherapy (single or doublet) or BSC in chemotherapy‐naive patients with locally advanced or metastatic (stage IIIB or IV) EGFR M+ NSCLC unsuitable for treatment with curative intent. Data collection and analysis Two review authors independently identified articles, extracted data, and carried out the 'Risk of bias' assessment. We conducted meta‐analyses using a fixed‐effect model unless there was substantial heterogeneity, in which case we also performed a random‐effects analysis as a sensitivity analysis. Main results Nineteen trials met the inclusion criteria. Seven of these exclusively recruited people with EGFR M+ NSCLC; the remainder recruited a mixed population and reported results for people with EGFR M+ NSCLC as subgroup analyses. The number of participants with EGFR M+ tumours totalled 2317, of whom 1700 were of Asian origin. Overall survival (OS) data showed inconsistent results between the included trials that compared EGFR‐targeted treatments against cytotoxic chemotherapy or placebo. Erlotinib was the intervention treatment used in eight trials, gefitinib in seven trials, afatinib in two trials, and cetuximab in two trials. The findings of one trial (FASTACT 2) did report a statistically significant OS gain for participants treated with erlotinib plus cytotoxic chemotherapy when compared to cytotoxic chemotherapy alone, but this result was based on a small number of participants (n = 97). For progression‐free survival (PFS), a pooled analysis of 3 trials (n = 378) demonstrated a statistically significant benefit for erlotinib compared with cytotoxic chemotherapy (hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.24 to 0.38). In a pooled analysis with 491 participants administered gefitinib, 2 trials (IPASS and NEJSG) demonstrated a statistically significant PFS benefit of gefitinib compared with cytotoxic chemotherapy (HR 0.39; 95% CI 0.32 to 0.48). Afatinib (n = 709) showed a statistically significant PFS benefit when compared with chemotherapy in a pooled analysis of 2 trials (HR 0.42; 95% CI 0.34 to 0.53). Commonly reported grade 3/4 adverse events for afatinib, erlotinib, and gefitinib monotherapy were rash and diarrhoea. Myelosuppression was consistently worse in the chemotherapy arms, fatigue and anorexia were also associated with some chemotherapies. No statistically significant PFS or OS benefit for cetuximab plus cytotoxic chemotherapy (n = 81) compared to chemotherapy alone was reported in either of the two trials. Six trials reported on quality of life and symptom improvement using different methodologies. For each of erlotinib, gefitinib, and afatinib, 2 trials showed improvement in one or more indices for the tyrosine‐kinase inhibitor (TKI) compared to chemotherapy. The quality of evidence was high for the comparisons of erlotinib and gefitinib with cytotoxic chemotherapy and for the comparison of afatinib with cytotoxic chemotherapy. Authors' conclusions Erlotinib, gefitinib, and afatinib are all active agents in EGFR M+ NSCLC patients, and demonstrate an increased tumour response rate and prolonged progression‐free survival compared to cytotoxic chemotherapy. We also found a beneficial effect of the TKI compared to cytotoxic chemotherapy. However, we found no increase in overall survival for the TKI when compared with standard chemotherapy. Cytotoxic chemotherapy is less effective in EGFR M+ NSCLC than erlotinib, gefitinib, or afatinib and is associated with greater toxicity. There were no data supporting the use of monoclonal antibody therapy
Positive- and negative peer modelling effects on young children's consumption of novel blue foods.
ObjectiveThe effects of positive- and negative peer modelling on children's consumption of a novel blue food, presented in each of four snack meals during an "activity" day, were evaluated. It was predicted that: (i) novel food consumption would increase after positive modelling, but decrease after negative modelling; (ii) modelling effects would generalise to a second novel blue food when participants were alone when they ate their snack; (iii) that positive modelling would reverse the effects of negative modelling.DesignA mixed design was employed with random assignment to either Groups A, B, or C (equal numbers of males and females per group). Within groups, each participant received the novel food on four snack occasions. Group A received positive modelling of blue food consumption on the first and third occasions, but were alone when they received the foods on the second and fourth occasions; Group B had negative modelling on the first occasion, positive modelling on the third, and ate alone on the second and fourth; Group C ate alone on all four occasions. To measure generalisation, an additional blue food was presented in all second and fourth "alone" occasions.ParticipantsThirty-five 5-7-year olds took part in Study 1, and 44 3-4-year olds in Study 2.ResultsAll main predictions were confirmed except that positive peer modelling did not reverse the effects of negative modelling in the 3-4-year olds.ConclusionNegative peer modelling inhibits novel food consumption, and its effects are particularly difficult to reverse in younger children
A systematic review of lenvatinib and sorafenib for treating progressive, locally advanced or metastatic, differentiated thyroid cancer after treatment with radioactive iodine
Drug-eluting stents versus bare-metal stents for stable ischaemic heart disease
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the benefits and harms of drug‐eluting stents versus bare‐metal stents in participants with stable ischaemic heart disease
Cladribine Tablets for the First-Line Treatment of Relapsing-Remitting Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
Paclitaxel as Albumin-Bound Nanoparticles with Gemcitabine for Untreated Metastatic Pancreatic Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal
As part of the single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited Celgene Ltd to submit clinical and cost-effectiveness evidence for paclitaxel as albumin-bound nanoparticles (Nab-Pac) in combination with gemcitabine (Nab-Pac + Gem) for patients with untreated metastatic pancreatic cancer. The STA was a review of NICE's 2015 guidance (TA360) in which Nab-Pac + Gem was not recommended for patients with untreated metastatic pancreatic cancer. The review was prompted by a proposed Patient Access Scheme (PAS) discount on the price of Nab-Pac and new evidence that might lead to a change in the guidance. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group (ERG). This article summarises the ERG's review of the company's evidence submission for Nab-Pac + Gem, and the Appraisal Committee (AC) decision. The final scope issued by NICE listed three comparators: gemcitabine monotherapy (Gem), gemcitabine in combination with capecitabine (Gem + Cap), and a combination of oxaliplatin, irinotecan, leucovorin and fluorouracil (FOLFIRINOX). Clinical evidence for the comparison of Nab-Pac + Gem versus Gem was from the phase III CA046 randomized controlled trial. Analysis of progression-free survival (PFS) and overall survival (OS) showed statistically significant improvement for patients treated with Nab-Pac + Gem versus Gem. Clinical evidence for the comparison of Nab-Pac + Gem versus FOLFIRINOX and versus Gem + Cap was derived from a network meta-analysis (NMA). Results of the NMA did not indicate a statistically significant difference in OS or PFS for the comparison of Nab-Pac + Gem versus either Gem + Cap or FOLFIRINOX. The ERG's main concerns with the clinical effectiveness evidence were difficulties in identifying the patient population for whom treatment with Nab-Pac + Gem is most appropriate, and violation of the proportional hazards (PH) assumption in the CA046 trial. The ERG highlighted methodological issues in the cost-effectiveness analysis pertaining to the modelling of survival outcomes, estimation of drug costs and double counting of adverse-event disutilities. The AC accepted all the ERG's amendments to the company's cost-effectiveness model; however, these did not make important differences to the incremental cost-effectiveness ratios (ICERs). The company's base-case ICER was £46,932 per quality-adjusted life-year (QALY) gained for the comparison of Nab-Pac + Gem versus Gem. Treatment with Nab-Pac + Gem was dominated both by treatment with Gem + Cap and with FOLFIRINOX in the company's base case. The AC concluded that the most plausible ICER for treatment with Nab-Pac + Gem versus Gem was in the range of £41,000-£46,000 per QALY gained. The AC concluded that Nab-Pac + Gem was not cost effective compared with Gem + Cap or FOLFIRINOX, and accepted that treatment with Nab-Pac + Gem met the end-of-life criteria versus Gem but did not consider Nab-Pac + Gem to meet the end-of-life criteria compared with Gem + Cap or FOLFIRINOX. The AC also concluded that although patients who would receive Nab-Pac + Gem rather than FOLFIRINOX or Gem + Cap were difficult to distinguish, they were identifiable in clinical practice. The AC recommended treatment with Nab-Pac + Gem for patients with untreated metastatic pancreatic cancer for whom other combination chemotherapies were unsuitable and who would otherwise receive Gem