Immunotherapy in Patients with Advanced Non-Small-Cell Lung Cancer Under-Represented by Clinical Trials.

Since the initial US FDA approval of an immune checkpoint inhibitor (ICI) for the treatment of non-oncogene-driven non-small-cell lung cancer (NSCLC) nine years ago, this therapeutic strategy has been cemented as a crucial component of treatment for most of these patients. However, there is a clear efficacy-effectiveness gap whereby patients in the 'real world' seem to have more modest clinical outcomes compared to those enrolled in landmark clinical trials. This gap may be driven by the under-representation of important patient populations, including populations defined by clinical or molecular characteristics.

Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer.

Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival.

Materials And Methods: A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020.

Imaging response to immune checkpoint inhibitors in patients with advanced melanoma: a retrospective observational cohort study.

Background: The association between objective imaging response and first line immune checkpoint inhibitor (ICI) therapy regimes in advanced melanoma remains uncharacterized in routine practice.

Methods: We conducted a multi-center retrospective cohort analysis of advanced melanoma patients receiving first line ICI therapy from August 2013-May 2020 in Alberta, Canada. The primary outcome was likelihood of RECIST v1.

Characteristics of clinician input in Canadian funding decisions for cancer drugs: a cross-sectional study based on CADTH reimbursement recommendations.

Objective: To examine characteristics of clinician input to the pan-Canadian Oncology Drug Review (pCODR) for cancer drug funding recommendations from 2016 to 2020.

Design, Setting And Participants: Descriptive, cross-sectional study including 62 reimbursement decisions from pCODR from 2016 to 2020.

Interventions: pCODR recommendations were analysed for the number of clinicians consulted on each submission, affiliation, number of submissions per clinician, declared financial conflicts of interest (FCOIs), randomisation, type of blinding, primary endpoint, study phase, and whether the study demonstrated improvement in overall survival (OS) and progression-free survival (PFS).

Impact of Performance Status on Survival Outcomes and Health Care Utilization in Patients With Advanced NSCLC Treated With Immune Checkpoint Inhibitors.

Introduction: Landmark trials testing immune checkpoint inhibitors (ICIs) in advanced NSCLC are difficult to extrapolate to real-world practice given the exclusion of patients with poor (i.e., ≥2) Eastern Cooperative Oncology Group performance status (ECOG PS).

Association of Immune-Related Adverse Events, Hospitalization, and Therapy Resumption With Survival Among Patients With Metastatic Melanoma Receiving Single-Agent or Combination Immunotherapy.

Importance: Immune-related adverse events (irAEs) due to immune checkpoint blockade (ICB) have been shown to be positively associated with survival. Among patients with metastatic melanoma, evidence supporting this association has been conflicting, while ipilimumab-nivolumab combination ICB has been examined only in small clinical cohorts.

Objective: To examine the association between irAEs and survival among patients with metastatic melanoma, in particular for those receiving combination ICB.

Clinical Factors Associated with Long-Term Survival in Metastatic Melanoma Treated with Anti-PD1 Alone or in Combination with Ipilimumab.

Immune checkpoint inhibitors (ICIs) for treatment of metastatic melanoma (MM) offer lasting overall survival (OS) benefit in a subset of patients. However, outcomes remain poor for non-responders. Clinical predictors of long-term survival remain elusive.

Industry Relationships With Medical Oncologists: Who Are the High-Payment Physicians?

Purpose: Many oncologists have relationships with industry. Previous work has shown that these payments are usually modest; however, there exist a subset of medical oncologists who receive more than $100,000 US dollars (USD) annually. Here, we describe the characteristics of these physicians.

Industry payments to US physicians for cancer therapeutics: An analysis of the 2016-2018 open payments datasets.

Background: Many oncologists who lead guidelines and clinical trials have financial conflicts of interest (fCOI) with industry. However, the extent to which fCOI reaches all cancer care providers is not known. Here we describe industry payments across all cancer care specialties by specific drug.

Challenges with sex-specific subgroup analyses in oncology clinical trials for drug approvals between 2015-2020.

Introduction: Women continue to be underrepresented in oncology clinical trials, leading to poor, underpowered subgroup analyses that cannot be generalized to cancer patients in practice. In 2014, the US Food and Drug Administration (FDA) released an Action Plan, which included actions to improve the quality and reporting of demographic subgroup data. We sought to evaluate the five-year progress since the release of this report by assessing the credibility of sex-specific subgroup analyses in oncology clinical trials.

The Role of Immunotherapy in the Treatment of Malignant Pleural Mesothelioma.

Malignant pleural mesothelioma is a rare and aggressive malignancy arising from mesothelial cells that line the serous membranes of the body. Cytotoxic chemotherapy has been a mainstay of therapy, resulting in a modest improvement in overall survival, but toxicity limits the eligible patient population. Few targeted agents beyond bevacizumab have demonstrated superior efficacy compared to placebos.

Effectiveness and Safety of First-Line Pembrolizumab in Older Adults with PD-L1 Positive Non-Small Cell Lung Cancer: A Retrospective Cohort Study of the Alberta Immunotherapy Database.

The emergence of immunotherapy revolutionized the treatment of non-small-cell-lung cancer (NSCLC), with multiple landmark clinical trials establishing the efficacy of these agents. However, many patients who receive immunotherapy in clinical practice would be considered clinical trial ineligible. One such population that is often under-represented in clinical trials is older adults.

Trends in drug revenue among major pharmaceutical companies: A 2010-2019 cohort study.

Background: Over the past 2 decades there has been a substantial increase in the number of new cancer medicines; this has been accompanied by a dramatic rise in drug costs. It is unknown how these trends impact the revenue of the pharmaceutical sector.

Methods: Retrospective cohort study to characterize temporal trends of revenue generated from cancer medicines as a proportion of total drug revenue among 10 large pharmaceutical companies from 2010 to 2019.

The Inclusion of Women in Global Oncology Drug Trials Over the Past 20 Years.

This cohort study reviews enrollment patterns of completed cancer drug trials over the past 20 years to compare sex-specific trial participation with current cancer incidence rates.

Outcomes of patients with solid tumour malignancies treated with first-line immuno-oncology agents who do not meet eligibility criteria for clinical trials.

Background: Immuno-oncology (IO)-based therapies have been approved based on randomised clinical trials, yet a significant proportion of real-world patients are not represented in these trials. We sought to compare the outcomes of trial-ineligible vs. -eligible patients with advanced solid tumours treated with first-line (1L) IO therapy.

Evaluation of the modified immune prognostic index to prognosticate outcomes in metastatic uveal melanoma patients treated with immune checkpoint inhibitors.

Background: Metastatic uveal melanoma (MUM) is associated with poor survival and inferior response to immune checkpoint inhibitor (ICI) therapy when compared with metastatic cutaneous melanoma. Currently, prognostic biomarkers are lacking to guide treatment decisions.

Patients And Methods: We conducted a multicenter, retrospective cohort study using a centralized, province-wide cancer database in Alberta, Canada.

Evaluation of the Clinical Benefit of Cancer Drugs Submitted for Reimbursement Recommendation Decisions in Canada.

Importance: Cancer drugs approved by the US Food and Drug Administration have come under scrutiny for marginal clinical benefits; however, the clinical benefits of cancer drugs recommended for reimbursement in Canada have not been adequately studied.

Objective: To assess the differences in the clinical evidence and benefit of cancer drugs that received a positive vs a negative recommendation for provincial reimbursement in Canada.

Design, Setting, And Participants: This cohort study obtained publicly available regulatory documents from the pan-Canadian Oncology Drug Review (pCODR) and corresponding clinical trial documentation.

Oncology education for family medicine residents: a national needs assessment survey.

Background: This study aimed to determine the current state of oncology education in Canadian family medicine postgraduate medical education programs (FM PGME) and examine opinions regarding optimal oncology education in these programs.

Methods: A survey was designed to evaluate ideal and current oncology teaching, educational topics, objectives, and competencies in FM PGMEs. The survey was sent to Canadian family medicine (FM) residents and program directors (PDs).

Second-line treatment of hepatocellular carcinoma after sorafenib: Characterizing treatments used over the past 10 years and real-world eligibility for cabozantinib, regorafenib, and ramucirumab.

Background: The CELESTIAL, RESORCE, and REACH-2 trials showed survival benefit of cabozantinib, regorafenib, and ramucirumab, respectively, in hepatocellular carcinoma (HCC) patients treated with sorafenib who had good performance status (ECOG 0-1) and liver function (Child-Pugh-A). This study characterizes subsequent treatments received by HCC patients after sorafenib, and determines the proportion of patients eligible for novel therapies if strict eligibility criteria (SEC) were utilized compared to more liberal modified eligibility criteria (MEC, including ECOG 2, Child-Pugh-B7).

Methods: HCC patients who received sorafenib between 2008 and 2017 were included from the Canadian HCC CHORD Database.

The Lung Immune Prognostic Index Discriminates Survival Outcomes in Patients with Solid Tumors Treated with Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of several solid tumor types. However, as patient outcomes are heterogeneous, clinical tools to aid in prognostication are needed. The Lung Immune Prognostic Index (LIPI) correlates with outcomes in patients with non-small cell lung cancer (NSCLC) treated with ICI, but its applicability beyond NSCLC is poorly defined.