ABSTRACT
BACKGROUND: Phase 1 oncology trials provide access to new therapies and may improve cancer outcomes. Phase 1 trials conducted in the Asian-Pacific region are increasing at a faster rate than the global trend. This study aimed to describe the changing landscape of phase 1 oncology trials in Australia in the last decade. METHODS: This cross-sectional study reviewed phase 1 oncology trials registered on ClinicalTrials.gov conducted in Australia. Phase 1 trials were included for analysis if they enrolled adults with solid organ malignancies, used at least one systemic agent, and were first registered between January 1, 2012, and December 31, 2022. The number of trials, site locations, sponsor type, and drug class were analyzed using descriptive statistics. RESULTS: Over the 10-year period, ClinicalTrials.gov included 493 phase 1 clinical trials across 71 Australian sites. Most sites were in metropolitan locations; in Melbourne, trials were concentrated within selected sites, while in Sydney, trials were spread across a larger number of sites. The number of phase 1 trials per annum increased from 18 in 2012 to 75 in 2022. Since 2020, emerging biopharmaceutical companies have become the predominant sponsor type, a trend that is also seen globally. While most trial sponsors were North American (42%), there was increasing representation from Asian sponsors over the 10-year period (6% in 2012 to 39% in 2022). Immunomodulatory (45%) and targeted approaches (44%) accounted for most drug classes used alone or in combination. CONCLUSIONS: There are an increasing number of phase 1 trials conducted within Australia. Sponsors of phase 1 trials are increasingly from Asian countries and are more likely to be emerging biopharmaceutical companies.
ABSTRACT
BACKGROUND: Overall survival (OS) results from randomized control trials (RCT) provide the strongest evidence for efficacy of anti-cancer treatments but can take a considerable amount of time to mature. Progression free survival (PFS) and objective response rate (ORR) are used as an early surrogate of OS treatment effect however their validity remains unclear. Our study aims to comprehensively evaluate ORR and PFS as surrogates for OS treatment effect across tumor groups and treatment types. MATERIAL AND METHODS: Phase 3 RCTs in solid malignancies that reported OS/PFS and ORR published between 1st of January 2010 and 30th of June 2022 were evaluated. The relationship of surrogate endpoints and OS treatment effect was assessed via weighted linear regression. The coefficient of determination (R2) quantified the fit of the regression model. RESULTS: 675 phase 3 RCT comprising of 350 112 patients were analysed. ORR (R2 of 0.10) and PFS (R2 of 0.38) were poor surrogate markers of OS treatment effect. The strength of surrogacy differed within treatment and tumour groups. PFS had the highest R2 for chemotherapy (0.56) and lowest for targeted therapy (0.40). PFS had the highest level of surrogacy for melanoma (R2 = 0.72) and pancreatic cancer (R2 = 0.70) compared to other tumour groups. Importantly ORR and PFS were also poorly correlated to each other (R2 = 0.33). CONCLUSIONS: ORR and PFS were poor trial-level surrogate markers of OS. The surrogacy performance of ORR and PFS differed by treatment and malignancy sub-type.
Subject(s)
Melanoma , Pancreatic Neoplasms , Humans , Biomarkers , Disease-Free Survival , Pancreatic Neoplasms/drug therapy , Progression-Free Survival , Randomized Controlled Trials as Topic , Clinical Trials, Phase III as TopicABSTRACT
OBJECTIVE: Direct oral anticoagulants (DOAC) are now considered an effective treatment option for cancer associated thrombosis (CAT). There are still controversies in the use of DOACs in CAT associated with gastrointestinal (GI) malignancies. BACKGROUND: Patients with GI malignancies and CAT present several unique management challenges. Factors such as the risk of bleeding from intact luminal primary, impact on absorption and efficacy of the DOACs due to altered anatomy, chemotherapy-induced nausea and vomiting, the potential drug to drug interactions need to be considered when prescribing DOACs in CAT associated with GI malignancies. METHODS: The landmark randomised controlled trials (RCTs), systematic reviews and observational studies (OSs) of real-world data comparing DOACs with low molecular weight heparin (LMWH) in treating CAT comprised heterogeneous groups of tumour sites with limited numbers of patients with GI malignancies. This article reviews the available evidence on outcomes of the subset of CAT associated with GI malignancies in recent RCTs. CONCLUSIONS: Future prospective trials need to evaluate the impact of the factors mentioned above in the efficacy of DOACs in preventing and treating CATs in specific subsets of GI malignancies. Until more evidence is available, LMWH is a more reasonable choice in selected subgroups of CAT in GI malignancies.
