PURPOSE: There is strong interest from patients, researchers, the pharmaceutical industry, medical journal editors, funders of research, and regulators in sharing clinical trial data for secondary analysis. However, data access remains a challenge because of concerns about patient privacy. It has been argued that synthetic data generation (SDG) is an effective way to address these privacy concerns. There is a dearth of evidence supporting this on oncology clinical trial data sets, and on the utility of privacy-preserving synthetic data. The objective of the proposed study is to validate the utility and privacy risks of synthetic clinical trial data sets across multiple SDG techniques. METHODS: We synthesized data sets from eight breast cancer clinical trial data sets using three types of generative models: sequential synthesis, conditional generative adversarial network, and variational autoencoder. Synthetic data utility was evaluated by replicating the published analyses on the synthetic data and assessing concordance of effect estimates and CIs between real and synthetic data. Privacy was evaluated by measuring attribution disclosure risk and membership disclosure risk. RESULTS: Utility was highest using the sequential synthesis method where all results were replicable and the CI overlap most similar or higher for seven of eight data sets. Both types of privacy risks were low across all three types of generative models. DISCUSSION: Synthetic data using sequential synthesis methods can act as a proxy for real clinical trial data sets, and simultaneously have low privacy risks. This type of generative model can be one way to enable broader sharing of clinical trial data.

PURPOSE: The HER2CLIMB-05 study (ClinicalTrials.gov identifier: NCT05132582 ) is investigating the efficacy and safety of adding tucatinib to trastuzumab and pertuzumab as first-line (1L) maintenance therapy in patients with human epidermal growth factor receptor 2–positive (HER2+) metastatic breast cancer (MBC). METHODS: Patients with centrally confirmed HER2+ MBC without evidence of progression post induction therapy and no or asymptomatic brain metastases (BM) were enrolled. Patients were randomly assigned 1:1 to tucatinib (300 mg) or placebo twice a day combined with trastuzumab/pertuzumab. The primary end point is investigator-assessed progression-free survival (PFS); secondary end points include overall survival (OS), PFS per blinded independent central review, CNS-PFS, and safety. RESULTS: Between March 2022 and July 2024, 654 patients were randomly assigned to tucatinib (n = 326) and placebo (n = 328) arms. All patients were female (median age, 54 years), 69.3% had de novo MBC, 52.6% were hormone receptor–positive, and 12.4% had presence/history of baseline BM. In this primary analysis, PFS was statistically significantly improved with addition of tucatinib versus placebo (hazard ratio, 0.641 [95% CI, 0.514 to 0.799]; P < .0001; median PFS: 24.9 v 16.3 months); a PFS benefit was seen regardless of the presence/absence of BM or hormone receptor status. OS data remain immature. The most common treatment-emergent adverse events (TEAEs) in the tucatinib arm were diarrhea (72.7%), nausea (33.1%), and elevated liver enzymes (ALT: 28.2%; AST: 25.8%), of which 6.1%, 0.9%, 13.5%, and 7.1%, respectively, were grade ≥3. In the tucatinib arm, 13.5% discontinued tucatinib because of TEAEs. CONCLUSION: Tucatinib addition to trastuzumab and pertuzumab demonstrated improvement in PFS with no new safety signals identified and may be an option for 1L maintenance therapy in patients with HER2+ MBC.

Most patients diagnosed with and dying from cancer in Canada are older adults, with aging contributing to the large projected growth in cancer incidence. Older adults with cancer have unique needs, and on a global scale increasing efforts have been made to address recognized gaps in their cancer care. However, in Canada, geriatric oncology remains a new and developing field. There is increasing recognition of the value of geriatric oncology and there is a growing number of healthcare providers interested in developing the field. While there is an increasing number of dedicated programs in geriatric oncology, they remain limited overall. Developing novel methods to delivery geriatric care in the oncology setting and improving visibility is important. Formal incorporation of a geriatric oncology curriculum into training is critical to both improve knowledge and demonstrate its value to healthcare providers. Although a robust group of dedicated researchers exist, increased collaboration is needed to capitalize on existing expertise. Dedicated funding is critical to promoting clinical programs, research, and training new clinicians and leaders in the field. By addressing challenges and capitalizing on opportunities for improvement, Canada can better meet the unique needs of its aging population with cancer and ultimately improve their outcomes.

Older patients with lower-risk hormone receptor-positive (HR+) breast cancer are frequently offered both radiotherapy (RT) and endocrine therapy (ET) after breast-conserving surgery (BCS). A survey was performed to assess older patients’ experiences and perceptions regarding RT and ET, and participation interest in de-escalation trials. Of the 130 patients approached, 102 eligible patients completed the survey (response rate 78%). The median age of respondents was 74 (interquartile range 71–76). Most participants (71%, 72/102) received both RT and ET. Patients felt the role of RT and ET, respectively, was to: reduce ipsilateral tumor recurrence (91%, 90/99 and 62%, 61/99) and improve survival (56%, 55/99 and 49%, 49/99). More patients had significant concerns regarding ET (66%, 65/99) than RT (39%, 37/95). When asked which treatment had the most negative effect on their quality of life, the results showed: ET (35%, 25/72), RT (14%, 10/72) or both (8%, 6/72). Participants would rather receive RT (57%, 41/72) than ET (43%, 31/72). Forty-four percent (44/100) of respondents were either, “not comfortable” or “not interested” in participating in potential de-escalation trials. Although most of the adjuvant therapy de-escalation trials evaluate the omission of RT, de-escalation studies of ET are warranted and patient centered.

The time of day of administration (chronotherapy) of certain medications can affect both their toxicity and efficacy. In this pragmatic, multicenter trial, women starting adjuvant endocrine therapy (ET) for hormone receptor-positive early-stage breast cancer were randomized (1:1) to either morning or evening administration. The primary endpoint was endocrine toxicity/tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline to 12-weeks. Secondary endpoints included: endocrine toxicity/tolerability and quality of life (FACT-ES and FACT-B) from baseline to 4, 8, 12, and 52 weeks, non-persistence or non-adherence, and patient preference for timing of ET. Between June 30, 2021, and March 18, 2022, 245 eligible participants were randomized to either morning (122/245, 49.8%) or evening ET (123/245, 50.2%). In the overall population, there was no statistical difference in the change in total FACT-ES score from baseline to 12 weeks (p = 0.086). There were no statistically significant differences for any of the secondary endpoints between the two groups. The study provides evidence for the enthusiasm of patients and investigators to take part in chronotherapy studies. Additional prospective studies should be performed to assess how the timing of ET affects survival outcomes to ensure optimal patient care. Trial Registration: ClinicalTrials.gov, NCT04864405.