Response rate by geographic region in patients with hormone receptor-positive, human epidermal growth factor receptor-2–negative advanced breast cancer from the SOLAR-1 trial

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RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis

Abstract Background RECORD-4 assessed everolimus in patients with metastatic renal cell carcinoma (mRCC) who progressed after 1 prior anti-vascular endothelial growth factor (VEGF) or cytokine and reinforced the clinical benefit of second-line everolimus. Because of the high percentage of patients from China enrolled in RECORD-4 (41%) and some reported differences in responses to certain targeted agents between Chinese and Western patients, this subanalysis evaluated outcomes in Asian versus non-Asian patients. Methods RECORD-4 enrolled patients with clear cell mRCC into 3 cohorts based on prior first-line therapy: sunitinib, other anti-VEGF (sorafenib, bevacizumab, pazopanib, other), or cytokines. Patients received everolimus 10 mg/d until progression of disease (RECIST, v1.0) or intolerance. Primary end point was progression-free survival per investigator review. Data cutoff was Sept 1, 2014. Results Among Asian (n = 55) versus non-Asian (n = 79) patients, 98% versus 84% had good/intermediate MSKCC prognosis; 73% versus 65% were men, and 85% versus 73% were < 65 years of age. All (100%) Asian patients were of Chinese ethnicity. Median duration of exposure was 5.5 mo for Asian and 6.0 mo for non-Asian patients. Among Asian versus non-Asian patients, median progression-free survival (months) was 7.4 versus 7.8 overall, 7.4 versus 4.0 with prior sunitinib, and 5.7 versus 9.2 with prior other anti-VEGFs. Clinical benefit rate was similar between populations: 74.5% (95% CI 61.0–85.3) for Asian patients and 74.7% (95% CI 63.6–83.8) for non-Asian patients. Most patients achieved stable disease as best overall response (Asian, 63.6%; non-Asian, 69.6%). Overall rate of grade 3/4 adverse events appeared similar for Asian (58%) and non-Asian patients (54%). Conclusions This RECORD-4 subanalysis demonstrated comparable efficacy and adverse event profiles of second-line everolimus in Asian and non-Asian patients. Efficacy and safety outcomes by prior therapy should be interpreted with caution because of small patient numbers in some subpopulations. Trial registration Everolimus as Second-line Therapy in Metastatic Renal Cell. Carcinoma (RECORD-4); ClinicalTrials.gov identifier: NCT01491672. Registration date: December 14, 2011

Heavy Episodic Drinking in Europe:A Cross Section Study in Primary Care in Six European Countries

Aims: We examined the prevalence of heavy episodic drinking in general practice attenders who were non-hazardous drinkers, the associated risk factors and the outcome over 6 months. Methods: Consecutive attenders aged 18-75 were recruited from the UK, Spain, Slovenia, Estonia, the Netherlands and Portugal and followed up after 6 months. Data were collected on alcohol use using the Alcohol Use Disorder Identification test (at recruitment and 6 months) and risk factors for heavy episodic alcohol use at recruitment. Results: The prevalence of heavy episodic drinking in non-hazardous drinkers was 4.5% across Europe [lowest in Portugal (1.5%); highest Netherlands (8.4%)]. It was less frequent in Spain, Slovenia, Estonia and Portugal compared with the UK and Netherlands. It was higher in men [odd ratio (OR) 4.4, 95% confidence interval (CI) 3.3, 5.9], people between 18 and 29 years of age, those employed (OR 1.8, 95% CI 1.3, 2.6) and those using recreational drugs (OR 2.1, 95% CI 1.4, 3.3). It was lower in people with existing DSMIV major depression (OR 0.54, 95% CI 0.31, 0.96). Heavy episodic drinkers were more likely to become hazardous drinkers at 6 months (male: OR 7.2, 95% CI 4.1, 12.7; female: OR 9.4, 95% CI 4.3, 20.6). Conclusion: Women and men in the UK, men in the Netherlands and younger people in all countries are at the greatest risk of exhibiting heavy episodic drinking behaviours even in the absence of hazardous alcohol use. There is hence an urgent need for general practitioners to consider early detection and management of heavy episodic drinking behaviour in this population

Additional files 3: of RECORD-4 multicenter phase 2 trial of second-line everolimus in patients with metastatic renal cell carcinoma: Asian versus non-Asian population subanalysis

Table S3 Grade 3 and 4 adverse events reported by Asian and non-Asian patients in the overall population and in the first-line therapy cohorts. (DOCX 13 kb

Effectiveness of Alpelisib + Fulvestrant Compared with Real-World Standard Treatment Among Patients with HR+, HER2-, PIK3CA-Mutated Breast Cancer.

BackgroundThe BYLieve trial (NCT03056755) confirmed efficacy and safety of alpelisib with fulvestrant for hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC), after cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) with an aromatase inhibitor (AI) as immediate prior therapy. Further analyses were performed to compare efficacy from BYLieve with effectiveness of standard treatment in the real-world setting.Materials and methodsPatients who progressed on a CDK4/6i plus AI and were treated with alpelisib with fulvestrant in BYLieve were matched with a real-world patient cohort who received standard-of-care from a deidentified clinico-genomics database (CGDB). Primary and secondary endpoints were to compare progression-free survival (PFS), estimated by the Kaplan-Meier method, and the proportion of patients remaining progression-free at 6 months, respectively, between the two cohorts.ResultsA total of 855 patients with PIK3CA-mutant disease who had prior CDK4/6i plus hormone therapy were selected from the CGDB; further matching to 120 patients from BYLieve selected 95 patients without exposure to HER2-targeting agents, clinical study drug, or alpelisib. In unadjusted and postmatching results, primary and secondary endpoints favored treatment with alpelisib with fulvestrant in BYLieve more than standard treatments in the real-world cohort. Postadjustment, median PFS for patients treated with alpelisib in BYLieve was 7.3 versus 3.7 months in the real-world cohort, and 6-month PFS was 54.6% versus 40.1%, respectively.ConclusionMatched/weighted analysis comparing BYLieve with the real-world setting further supports the clinical benefit of alpelisib with fulvestrant for treatment of HR+, HER2-, PIK3CA-mutant ABC after CDK4/6i treatment.Implications for practiceApproximately 40% of patients with hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) have PIK3CA-mutated tumors, which have been associated with endocrine therapy resistance. Alpelisib, an α-selective phosphatidylinositol-3-kinase inhibitor, demonstrated significantly improved progression-free survival in SOLAR-1 and demonstrated clinical efficacy in BYLieve when combined with fulvestrant. Data are limited in comparing the efficacy of alpelisib combined with fulvestrant with effectiveness of standard therapy after CDK4/6i treatment. Using real-world data, this is the first analysis comparing alpelisib combined with fulvestrant with standard treatments for HR+, HER2-, PIK3CA-mutant ABC in the post-CDK4/6i setting

Do you want to stay single? Considerations on single arm trials in drug development and the post-regulatory space

Single arm trials (SAT), while not preferred, remain in use throughout the drug development cycle. They may be accepted by regulators in particular contexts (eg., oncology and in rare diseases) when potential effects of new treatments are very large and placebo treatment is unethical. However, in the post-regulatory space, SATs are common, and perhaps even more poorly suited to address the questions of interest. In this manuscript, we review regulator and HTA positions on SATs, further challenges posed by SATs to address research questions beyond regulators, evolving statistical methods to provide context for SATs, case studies where SATs could and could not address questions or interest, and communication strategies to influence decision making and optimize study design to address evidence needs

Additional file 1 of PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials

Additional file 1