Comparative Effectiveness of First-Line Selpercatinib versus Standard Therapies in Patients with RET-Activated Cancers: An Exploratory Interpatient Analysis of LIBRETTO-001.

Selpercatinib is indicated for locally advanced/metastatic -activated solid tumors after progression or following prior systemic therapies. Until the recently published data from LIBRETTO-431 and LIBRETTO-531, there were limited effectiveness data comparing selpercatinib with other first-line treatments in -activated non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC), and thyroid cancer (TC). This study analyzed patient data from LIBRETTO-001 and compared the outcomes (time to treatment discontinuation {TTD}, time to next treatment or death {TTNT-D}, time to progression {TTP}, and the objective response rate {ORR}) of first-line selpercatinib (selpercatinib arm) use with the outcomes of first-line standard therapies in patients who then received selpercatinib in later lines of treatment (comparator arm).

Real-world clinical profile, RET mutation testing, treatments, and PROs for MTC in Europe.

Objective: This study aimed to describe real-world patient and physician characteristics, rearranged during transfection (RET) mutation testing and results, treatment patterns, and patient-reported outcomes (PROs) in advanced or metastatic medullary thyroid cancer (aMTC) across five populous European countries.

Methods: Cross-sectional physician and patient surveys were used to collect quantitative and qualitative data in France, Germany, Italy, Spain, and the UK from July to December 2020, prior to the introduction of selective RET inhibitors in Europe. Physicians completed patient record forms and a survey about their specialty and practice site.

Bayesian survival extrapolation for cost-effectiveness analysis: a case study of RELAY for ramucirumab in combination with erlotinib in the treatment of non-small-cell lung cancer.

Aim: Increasing trend for progression-free survival (PFS)-based primary endpoint in oncology has led to lack of mature overall survival (OS) data at the time of approval. To address this evidence gap in economic evaluations, we used a joint Bayesian approach to predict survival outcomes using immature OS data from the RELAY trial.

Methods: Patient data from RELAY and systematic literature review (SLR) of phase 3 randomized clinical trials with hazard ratio (HR) estimates of mature PFS and immature OS were considered.

Optimizing the Dosing Regimen of Cetuximab and Ramucirumab Using the Model-Informed Drug Development Paradigm.

Model-informed drug development (MIDD) is a process that integrates drug exposure-based, biological, and statistical models to enhance the benefit-risk balance in drug development. The US Food and Drug Administration (FDA) MIDD Paired Meeting Pilot Program provides a platform to apply MIDD approaches to drug development and to seek regulatory feedback in a collaborative and streamlined process prior to submission for approval. Eli Lilly and Company (Lilly) participated in the Pilot Program to seek agency alignment to enhance the initial approved dosing regimens of cetuximab (Erbitux; Eli Lilly and Company, Indianapolis, IN) and ramucirumab (Cyramza; Eli Lilly and Company) without conducting additional clinical trials.

Physician- and patient-reported symptom concordance and association with quality of life in hepatocellular carcinoma.

To investigate the association of discordance in patient- and physician-reported symptoms on health-related quality of life (HRQoL) in hepatocellular carcinoma (HCC). Data were drawn from a point-in-time survey of physicians and patients conducted in Germany, Italy and Spain (October 2018 - January 2019). Physicians and their consulting patients independently reported baseline characteristics, symptoms, treatment history and satisfaction, and HRQoL derived using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire.

Efficacy and Safety of Cetuximab Dosing (biweekly vs weekly) in Patients with KRAS Wild-type Metastatic Colorectal Cancer: A Meta-analysis.

Background: Cetuximab 500 mg/m2 biweekly (Q2W) plus chemotherapy is commonly used and recommended by NCCN guidelines. This meta-analysis compares efficacy and safety between Q2W versus weekly (Q1W) cetuximab dosing.

Methods: A systematic literature review was performed on Pubmed and RightFind (2007-2017) for patients with KRAS wild-type mCRC who received Q2W or Q1W cetuximab and other treatments.

Patient-Reported Outcomes with Selpercatinib Among Patients with RET Fusion-Positive Non-Small Cell Lung Cancer in the Phase I/II LIBRETTO-001 Trial.

Background: LIBRETTO-001 is an ongoing, global, open-label, phase I/II study of selpercatinib in patients with advanced or metastatic solid tumors. We report interim patient-reported outcomes in patients with RET fusion-positive non-small cell lung cancer (NSCLC).

Patients And Methods: Patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30) version 3.

Patient-Reported Outcomes with Selpercatinib Treatment Among Patients with RET-Mutant Medullary Thyroid Cancer in the Phase I/II LIBRETTO-001 Trial.

Background: Medullary thyroid cancer (MTC) standard of care includes multikinase inhibitors (MKIs), which can exacerbate disease-related diarrhea, primarily because of non-RET kinase inhibition. We report diarrhea and other patient-reported outcomes (PROs) with selpercatinib, a highly selective RET inhibitor, among patients with RET-mutant MTC in the ongoing, phase I/II LIBRETTO-001 trial.

Materials And Methods: Instrument completion time points were baseline (cycle 1, day 1) and approximately every other 28-day cycle until cycle 13 (every 12 weeks thereafter) for the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, and baseline, weekly during cycle 1, and day 1 of every cycle for the modified Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT).

Quality of Life Associated with Ramucirumab Treatment in Patients with Advanced Gastric Cancer in Japan: Exploratory Analysis from the Phase III RAINBOW Trial.

Background And Objective: Gastric cancer has been associated with notable geographic heterogeneity in previous multi-regional studies. In particular, patients from Japan have better outcomes compared with patients from other regions. Here, we assess patient-focused outcomes for the subgroup of Japanese patients in the global RAINBOW study.

KRAS mutation as a prognostic factor and predictive factor in advanced/metastatic non-small cell lung cancer: A systematic literature review and meta-analysis.

KRAS (Kirsten Rat Sarcoma) is the most common oncogenic mutation detected in patients with non-small cell lung cancer (NSCLC). However, the role of KRAS as either a prognostic factor or predictive factor (modifier of treatment effects) in NSCLC is not well established at this time. This systematic literature review (SLR) and meta-analysis synthesized the available evidence regarding the role of KRAS mutation as a predictive factor and/or prognostic factor of survival and response outcomes in patients with advanced/metastatic (stage IIIB-IV) NSCLC.

Ramucirumab in elderly patients with hepatocellular carcinoma and elevated alpha-fetoprotein after sorafenib in REACH and REACH-2.

Background & Aims: Limited data on treatment of elderly patients with hepatocellular carcinoma (HCC) increase the unmet need. REACH and REACH-2 were global phase III studies of ramucirumab in patients with HCC after prior sorafenib, where patients with alpha-fetoprotein (AFP) ≥400 ng/mL showed an overall ssurvival (OS) benefit for ramucirumab. These post-hoc analyses examined efficacy and safety of ramucirumab in patients with HCC and baseline AFP ≥ 400 ng/mL by three prespecified age subgroups (<65, ≥65 to <75 and ≥75 years).

Relative efficacy of interventions in the treatment of second-line non-small cell lung cancer: a systematic review and network meta-analysis.

Background: Locally advanced or metastatic non-small cell lung cancer (NSCLC) that has progressed after first-line treatment has a poor prognosis. Recent randomized clinical trials (RCTs) have demonstrated survival benefits of alternative treatments to docetaxel. However, information is lacking on which patients benefit the most and what drug or regimen is optimal.

Is ramucirumab and paclitaxel therapy beneficial for second-line treatment of metastatic gastric or junctional adenocarcinoma for patients with ascites? Analysis of RAINBOW phase 3 trial data.

Purpose: Second-line treatment with ramucirumab-paclitaxel has demonstrated statistically significant and clinically meaningful survival outcomes compared to paclitaxel-alone in patients with advanced gastric cancer (HR=0.807, 95% CI 0.678-0.

Association between life-course socioeconomic position and inflammatory biomarkers in older age: a nationally representative cohort study in Taiwan.

Background: Evidence of an association between low socioeconomic position (SEP) and inflammatory markers is scant. This study aimed to examine how life-course SEP predicted C-reactive protein (CRP) and interleukin (IL-6) in older age from a national cohort.

Methods: We collected data from 1036 participants in the Social Environment and Biomarkers of Aging Study in Taiwan.

Deriving health utility values from a randomized, double-blind, placebo-controlled trial of siltuximab in subjects with multicentric Castleman's disease.

Purpose: To estimate health utility values, explore predictors of utility values, and estimate the quality-adjusted life years (Q.A.L.

The US hospital standardised mortality ratio: Retrospective database study of Massachusetts hospitals.

Objectives: To present a case-mix adjustment model that can be used to calculate Massachusetts hospital standardised mortality ratios and can be further adapted for other state-wide data-sets.

Design: We used binary logistic regression models to predict the probability of death and to calculate the hospital standardised mortality ratios. Independent variables were patient sociodemographic characteristics (such as age, gender) and healthcare details (such as admission source).

Assessing the burden of illness from cervical dystonia using the Toronto Western Spasmodic Torticollis Rating Scale scores and health utility: a meta-analysis of baseline patient-level clinical trial data.

Purpose: This study aimed to explore the burden of illness associated with cervical dystonia (CD), including possible demographic and humanistic correlates of baseline disease severity.

Methods: The analysis involved the five multinational randomized, placebo-controlled clinical trials that had evaluated the efficacy and safety of Dysport® in patients with CD, including assessment using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS). Patient-level TWSTRS scores from the individual studies were meta-analysed to estimate disease severity at baseline.

Logistic versus hierarchical modeling: an analysis of a statewide inpatient sample.

Background: Although logistic regression is traditionally used to calculate hospital standardized mortality ratio (HSMR), it ignores the hierarchical structure of the data that can exist within a given database. Hierarchical models allow examination of the effect of data clustering on outcomes.

Study Design: Traditional logistic regression and random intercepts fixed slopes hierarchical models were fitted to a dataset of patients hospitalized between 2005 and 2007 in Massachusetts.

The performance of automated case-mix adjustment regression model building methods in a health outcome prediction setting.

We have previously described a system for monitoring a number of healthcare outcomes using case-mix adjustment models. It is desirable to automate the model fitting process in such a system if monitoring covers a large number of outcome measures or subgroup analyses. Our aim was to compare the performance of three different variable selection strategies: "manual", "automated" backward elimination and re-categorisation, and including all variables at once, irrespective of their apparent importance, with automated re-categorisation.

Admission rates and in-hospital mortality for hip fractures in England 1998 to 2009: time trends study.

Background: Fractures of the proximal femur are an important public health concern. The incidence of hip fractures is an index of osteoporosis burden. There have been no recent studies examining national trends in hip fractures in England.

Trustful societies, trustful individuals, and health: An analysis of self-rated health and social trust using the World Value Survey.

This study analyses the relationships between self-rated health and both individual and mean national social trust, focusing on a variant of Wilkinson's hypothesis that individuals will be less healthy the greater the lack of social cohesion in a country. It employs multilevel modelling on World Values Survey data across 69 countries with a total sample of 160,436 individuals. The results show that self-rated health are positively linked to social trust at both country and individual levels after controlling for individual socio-demographic and income variables plus individual social trust; increased trust is associated with better health.

Ten-year trends in hospital admissions for adverse drug reactions in England 1999-2009.

Objectives: Adverse drug reactions (ADR) are an important cause of morbidity and mortality. We analysed trends in hospital admissions associated with ADRs in English hospitals between 1999 and 2008.

Design: Data from the Hospital Episode Statistics database were examined for all English hospital admissions (1999-2008) with a primary or secondary diagnosis of an ADR recorded.