Do female and male patients derive similar benefits from approved systemic oncology therapies? A systematic review and meta-analysis.

Purpose: The National Institutes of Health's policy for the inclusion of females in clinical research was a pivotal step towards the consideration of sex as a biological variable, which is of particular importance in oncology, given differential incidence and outcomes of cancer between the sexes, and known pharmacodynamic, pharmacokinetic, and immunological differences. Therefore, we aim to investigate if such biological sex-based differences translate to clinically meaningful outcome differences from recently approved systemic oncology therapies.

Methods: A systematic review of randomized control trials (RCTs) cited in Food and Drug Administration, European Medicines Agency, and Health Canada approvals was conducted.

Economic Evaluation of a Geriatric Oncology Clinic.

Geriatric assessment (GA) is supported by recent trials and guidelines yet rarely implemented due to a lack of resources. We performed an economic evaluation of a geriatric oncology clinic. Pre-GA proposed treatments and post-GA actual treatments were obtained from a detailed chart review of patients seen at a single academic centre.

Assessment of Food and Drug Administration- and European Medicines Agency-Approved Systemic Oncology Therapies and Clinically Meaningful Improvements in Quality of Life: A Systematic Review.

Importance: For patients with cancer treated with palliative intent, quality of life (QOL) is a critical aspect of treatment decision-making, alongside survival. However, regulatory approval can be based solely on survival measures or antitumor activities, without QOL evidence.

Objective: To investigate whether recently approved oncology therapies demonstrate clinically meaningful improvements in QOL.

Comparing Manufacturer Submitted and Pan-Canadian Oncology Drug Review Reanalysed Incremental Cost-Effectiveness Ratios for Novel Oncology Drugs.

Background: To determine the magnitude of difference between manufacturer-submitted and pan-Canadian Oncology Drug Review (pCODR) calculated incremental cost-effectiveness ratios (ICERs), incremental cost (ΔC), and incremental effectiveness (ΔE); to examine whether there is a significant difference in the proportion of ICERs deemed cost-effective; to evaluate trends in the ICERs over time; and to identify methodological issues in manufacturer-submitted economic models.

Methods: Economic guidance reports for all drug indications submitted from July 2011-November 2018 were extracted from the pCODR database. Cumulative distribution plots were constructed to compare the manufacturer-submitted economic values with both the pCODR lower- and upper-reanalyzed estimates.

Application of the ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale to Assess the Value of Abiraterone and Enzalutamide in Advanced Prostate Cancer.

Purpose: As novel hormonal therapies, such as abiraterone and enzalutamide, move into earlier stages of treatment of advanced prostate cancer, there are significant cost implications. We used the ASCO Value Framework (AVF) and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) to quantify and compare the incremental clinical benefit and costs of these agents in the metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) settings.

Methods: We searched PubMed for randomized phase III trials of abiraterone and enzalutamide in mCRPC and mCSPC.

Adjuvant treatment for resected pancreatic adenocarcinoma: A systematic review and network meta-analysis.

Adjuvant chemotherapy has significantly improved outcomes following surgical resection for pancreatic adenocarcinoma; however, the optimal adjuvant strategy remains unclear. This systematic review and network meta-analysis was conducted to provide indirect comparative evidence across adjuvant chemotherapies. Electronic searches of EMBASE, MEDLINE, Cochrane and ASCO databases were conducted to identify eligible randomized controlled trials (RCT).

Value-based pricing: Toward achieving a balance between individual and population gains in health benefits.

Objectives: Value-based pricing of oncology drugs provides a best estimate for the price of a drug, as it relates to the benefits it provides for individual patients. To date, the impact of value-based pricing to reference cost-effectiveness thresholds (λ) on individual and population-level health benefits remains uncharacterized. The current study examined the potential benefits of value-based pricing by quantifying the incremental net health benefit (INHB) of publicly funded oncology drugs, if funding occurred at manufacturer-submitted price without value-based pricing.

Estimating hazard ratios from published Kaplan-Meier survival curves: A methods validation study.

Objective: Various statistical methods have been developed to estimate hazard ratios (HRs) from published Kaplan-Meier (KM) curves for the purpose of performing meta-analyses. The objective of this study was to determine the reliability, accuracy, and precision of four commonly used methods by Guyot, Williamson, Parmar, and Hoyle and Henley.

Design: Pivotal randomized controlled trials (RCTs) in oncology were identified from the pan-Canadian Oncology Drug Review (pCODR) database (primary analysis) and the Food and Drug Administration's (FDA) drug approvals page (secondary analysis) between January 2012 and May 2016.

Assessment of Whether the American Society of Clinical Oncology's Value Framework and the European Society for Medical Oncology's Magnitude of Clinical Benefit Scale Measure Absolute or Relative Clinical Survival Benefit: An Analysis of Randomized Clinical Trials.

Importance: The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) have independently published value frameworks. To date, whether the clinical benefit scoring algorithms from these framework were intended to measure absolute or relative survival benefit remains unclear.

Objective: To empirically examine the measurement characteristics of these frameworks by comparing their survival efficacy components (ASCO clinical benefit score [CBS] and ESMO preliminary magnitude of clinical benefit grade [PMCBG]) with established measures of absolute (median survival difference and restricted mean survival time [RMST] difference) and relative (hazard ratios [HRs]) survival benefit.

Do older and younger patients derive similar survival benefits from novel oncology drugs? A systematic review and meta-analysis.

Background: older patients are commonly believed to derive less benefit from cancer drugs, even if they fulfil clinical trial eligibility [Talarico et al. (2004, J Clin Oncol, 22(22):4626-31)]. We aim to examine if novel oncology drugs provide differential age-based treatment outcomes for patients on clinical trials.

Examining Trends in Cost and Clinical Benefit of Novel Anticancer Drugs Over Time.

Purpose: The purpose of this study was to determine if clinical benefits of novel anticancer drugs, measured by the ASCO Value Framework and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale, have increased over time in parallel with increasing costs.

Methods: Anticancer drugs from phase III randomized controlled trials cited for clinical efficacy evidence in drug approvals between January 2006 to December 2015 were identified and scored using both frameworks. For each drug, the monthly price and incremental anticancer drug costs were calculated.

Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis.

The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016.

A network meta-analysis of the sequencing and types of systemic therapies with definitive radiotherapy in locally advanced squamous cell carcinoma of the head and neck (LASCCHN)☆.

Objectives: The current standard therapy for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) is platinum-based chemotherapy plus concurrent radiotherapy (CRT), but several systemic therapies have been evaluated. We performed a Bayesian network meta-analysis (NMA) with random effects to enable direct and indirect comparisons of all existing treatment modalities for LASCCHN simultaneously.

Material And Methods: A systematic review was conducted using MEDLINE, EMBASE, ASCO abstracts, ASTRO abstracts and the Cochrane Central of Registered Trials using Cochrane methodology to identify randomized controlled trials (RCTs) up to June 2016.

Cost-Effectiveness Analysis of Systemic Therapies in Advanced Pancreatic Cancer in the Canadian Health Care System.

Objectives: To assess the cost-effectiveness of gemcitabine (G), G + 5-fluorouracil, G + capecitabine, G + cisplatin, G + oxaliplatin, G + erlotinib, G + nab-paclitaxel (GnP), and FOLFIRINOX in the treatment of advanced pancreatic cancer from a Canadian public health payer's perspective, using data from a recently published Bayesian network meta-analysis.

Methods: Analysis was conducted through a three-state Markov model and used data on the progression of disease with treatment from the gemcitabine arms of randomized controlled trials combined with estimates from the network meta-analysis for the newer regimens. Estimates of health care costs were obtained from local providers, and utilities were derived from the literature.

Resistance to metronomic chemotherapy and ways to overcome it.

Therapeutic resistance is amongst the major determinants of cancer mortality. Contrary to initial expectations, antivascular therapies are equally prone to inherent or acquired resistance as other cancer treatment modalities. However, studies into resistance to vascular endothelial growth factor pathway inhibitors revealed distinct mechanisms of resistance compared to conventional cytotoxic therapy.

Antiangiogenic Therapy in Advanced Non-small-cell Lung Cancer: A Meta-analysis of Phase III Randomized Trials.

We conducted a meta-analysis to evaluate the efficacy of adding any antiangiogenic therapy (AT) to the standard of care in advanced non-small-cell lung cancer (NSCLC). The electronic databases Ovid PubMed, Cochrane Central Register of Controlled Trials, and Embase were searched to identify eligible trials. We included all phase III randomized trials with any line and type of treatment, histology.

High prevalence of potential drug-drug interactions in patients with castration-resistant prostate cancer treated with abiraterone acetate.

Purpose: Abiraterone acetate (AA), used to treat metastatic castration-resistant prostate cancer (mCRPC), inhibits androgen biosynthesis by blocking cytochrome P450 (CYP) 17A1. It also inhibits other cytochromes involved in the metabolism of various widely used medications. As such, there is presumably a high potential for drug-drug interactions (DDIs) that can diminish the efficacy of AA or concurrent medications, or increase the risk of DDI-related adverse events (AEs).

Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN.

Disease volume and distribution as drivers of treatment decisions in metastatic prostate cancer: From chemohormonal therapy to stereotactic ablative radiotherapy of oligometastases.

The prognosis of men with metastatic, castration-sensitive prostate cancer (CSPC) depends on both the distribution and extent of metastases, among other things. Patients with low-volume or oligometastatic disease have improved survival compared with those with high-volume metastases. While chemohormonal therapy is the new standard of care for men with high-volume metastatic CSPC, stereotactic ablative radiotherapy (SABR) is emerging as a promising treatment option with low toxicity for the management of oligometastatic CSPC.