Assessing the efficacy-effectiveness gap for cancer therapies: A comparison of overall survival and toxicity between clinical trial and population-based, real-world data for contemporary parenteral cancer therapeutics.

BACKGROUND: Although increasing evidence has suggested that an efficacy-effectiveness gap exists between clinical trial (CT) and real-world evidence (RWE), to the authors' knowledge, the magnitude of this difference remains undercharacterized. The objective of the current study was to quantify the magnitude of survival and toxicity differences between CT and RWE for contemporary cancer systemic therapies. METHODS: Patients receiving cancer therapies funded under Cancer Care Ontario's New Drug Funding Program (NDFP) were identified. Landmark CTs with data regarding survival and adverse events (AEs) for each drug indication were identified. RWE for survival and hospitalization rates during treatment were ascertained through Canadian population-based databases. The efficacy-effectiveness gap for each drug indication was calculated as the difference between RWE and CT data for median overall survival (OS), 1-year OS, and generated hazard ratios (HRs) with 95% CIs from Kaplan-Meier OS curves. Toxicity differences were calculated as the difference between RWE of hospitalization rates and CT serious AE rates. RESULTS: Twenty-nine indications from 20 systemic therapies were included. Twenty-eight of 29 indications (97%) demonstrated worse survival in RWE, with a median OS difference of 5.2 months (interquartile range, 3.0-12.1 months). Lower effectiveness in RWE also was demonstrated through a meta-analysis of an OS hazard ratio of 1.58 (95% CI, 1.39-1.80). The median difference between RWE for hospitalization rates and CT serious AEs was 14% (95% CI, 9%-22%). CONCLUSIONS: An efficacy-effectiveness gap exists for contemporary cancer systemic therapies, with a 5.2-month lower median OS observed in RWE compared with CT data. These data supports the use of RWE to better inform real-world decision making regarding the use of cancer systemic therapies.

Sarcopenia in Men With Bone-Predominant Metastatic Castration-Resistant Prostate Cancer Undergoing Ra-223 Therapy.

INTRODUCTION: Osteosarcopenia is the progressive loss of musculoskeletal structure and functionality, contributing to disability and mortality. Despite complex interactions between bone and muscle, osteosarcopenia prevention and treatment in men with metastatic castration-resistant prostate cancer (mCRPC) focuses predominantly on bone health. It is unknown whether Radium-223 (Ra-223) therapy affects sarcopenia. METHODS: We identified 52 patients with mCRPC who had received Ra-223 and had a baseline plus ≥1 follow-up abdominopelvic CT scan. The total contour area (TCA) and averaged Hounsfield units (HU) of the left and right psoas muscles were obtained at the inferior L3 endplate, and the psoas muscle index (PMI) was calculated therefrom. Intrapatient musculoskeletal changes were analyzed across various time points. RESULTS: TCA and PMI gradually declined over the study period (P = .002, P = .003, respectively), but Ra-223 therapy did not accelerate sarcopenia, nor the decline of HU compared to the pre-Ra-223 period. The median overall survival of patients with baseline sarcopenia was numerically worse (14.93 vs. 23.23 months, HR 0.612, P = .198). CONCLUSIONS: Ra-223 does not accelerate sarcopenia. Thus, worsening muscle parameters in men with mCRPC undergoing Ra-223 therapy are attributable to other factors. Further research is needed to determine whether baseline sarcopenia predicts poor overall survival in such patients.

Evaluating Patients' Perception of the Risk of Acute Care Visits During Systemic Therapy for Cancer.

PURPOSE: Unplanned emergency department (ED) visits and hospitalizations are common during systemic cancer therapy. To determine how patients with cancer trade off treatment benefit with risk of experiencing an ED visit or hospitalization when deciding about systemic therapy, we undertook a discrete choice experiment. MATERIALS AND METHODS: Patients with breast, colorectal, or head and neck cancer contemplating, receiving, or having previously received systemic therapy were presented with 10 choice tasks (5 in the curative and 5 in the palliative setting) that varied on 3 attributes: benefit, risk of ED visit, and risk of hospitalization. Preferences for attributes and levels were measured using part-worth utilities, estimated using hierarchical Bayes analysis. Segmentation analysis was conducted to identify subgroups with different preferences. RESULTS: A total of 293 patients completed the survey; most were female (76%), had breast cancer (63%), and were currently receiving systemic therapy (72%) with curative intent (59%). Benefit was the most important decision attribute regardless of treatment intent, followed by risk of hospitalization, then risk of ED visit. Two segments were observed: one large cluster exhibiting logical and consistent choices, and a smaller segment exhibiting illogical and inconsistent choices. Patients in the latter segment were more likely to have metastatic head and neck cancer, be male, were older, and reported fewer prior ED visits. CONCLUSION: Although the risk of ED visit or hospitalization contributes to patient treatment preferences, benefit was the most important attribute. Segmentation suggests that a subset of patients may lack cognitive abilities, engagement, or literacy to consistently evaluate treatment choices. Understanding this subset may provide insight into patients' decision making and understanding of treatment options.