Eligibility of real-world patients with metastatic breast cancer for clinical trials

Abstract

Introduction The results of clinical trials in metastatic breast cancer (MBC) are generalized to real-world patients. This study determines the proportion of real-world patients who would be eligible for clinical trials and compares outcomes in eligible versus ineligible patients. Methods Patients diagnosed with MBC from 2004 to 2015 in a large Canadian province were included. Patients with one of the following criteria were considered ineligible: the presence of comorbid conditions (anemia, uncontrolled diabetes, heart disease, liver disease, and kidney disease) or a history of immunosuppression or prior malignancy. The likelihood of receiving cancer therapy was analysed using logistic regression models and factors affecting overall survival (OS) were assessed by Cox proportional hazards models. Results A total of 1585 patients with MBC were identified. The median age at diagnosis was 63 years. Of these, 512 (32.3%) patients were deemed ineligible in whom the two most common reasons for ineligibility were renal dysfunction (17.2%), and previous immunosuppression (7.8%). In the real world, ineligible patients were less likely to receive chemotherapy (29.5% vs 45.8%; P < 0.001) but not radiation treatment (7.6% vs 9.6%; P = 0.196) or hormonal therapy (57.6% vs 60.6%; P = 0.261). The 5-year OS of ineligible patients who received systemic therapy in the real-world was significantly better than those who did not. Conclusions Despite being ineligible for clinical trials based on common eligibility criteria, many real-world patients receive systemic treatment and derive possible benefit. Broadening of inclusion criteria in clinical trials will enhance the representation of real-world patients and increase the generalizability of results.

A common goal to CARE: Cancer Advocates, Researchers, and Clinicians Explore current treatments and clinical trials for breast cancer brain metastases

“…In a subgroup analysis of the DESTINY-Breast01 trial, a phase 1 dose-finding study for trastuzumab deruxtecan (T-DXd), 24 of the 184 patients enrolled had stable CNS metastasis. The objective response rate was 58.3%, and median PFS was 18.1 months for these patients 71 . T-DM1, T-DXd, neratinib, and tucatinib are FDA-approved treatments for patients with HER2-positive MBC that has progressed on prior HER2-targeted therapy(ies).…”

Differences in Outcomes Between Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer Patients in Upper Middle-Income versus High-Income Countries: A Retrospective Study from 4 Oncology Centers

“…Many real-world patients receive systemic therapy and may benefit even if they don’t meet the standard eligibility requirements for clinical studies. The proportion of real-world patients in clinical trials will improve, and the results’ generalizability will rise when the inclusion criteria become widened [ 38 ]. Due to strict exclusion criteria, a substantial percentage of real-world patients are not eligible to take part in clinical trials, although many continue to receive therapy in everyday practice.…”

An Insight into Molecular Targets of Breast Cancer Brain Metastasis

“…Some of the drugs that target HER2/EGFR are Lapatinib (targets HER2 receptor), Trastuzumab (targets HER2 receptor), KD019 (targets HER2, Src, and EGFR), ARRY-380 (targets HER2 receptor), HKI-272 (targets HER1, HER2, and HER4 receptors), Afatinib (targets EGFR1, EGFR2, and EGFR4 receptors), and tucatinib (targets HER2 receptor). It is worth mentioning that tucatinib, a tyrosine kinase inhibitor, combined with trastuzumab and capecitabine, was approved by the USFDA on April 17, 2020, as a BCBM treatment regimen [ 38 , 99 , 100 ].…”

“…Tucatinib is a tyrosine kinase inhibitor, highly selective for the HER2 protein and can slightly inhibit the epidermal growth factor receptor [ 132 ]. Trastuzumab and capecitabine, in combination with tucatinib, demonstrated improved progression-free survival and enhanced CNS response in the BCBM treatment regimen [ 38 , 99 , 100 , 132 ]. Some recent studies also reported mTOR and PI3K inhibitors (Everolimus and Buparlisib (BKM120)) for the treatment of BCBM in combination with other anticancer drugs, such as trastuzumab and vinorelbine [ 38 , 133 ].…”