Current Oncology

As bispecific T-cell engagers (TCEs) gain traction in the oncology treatment landscape, cancer centres must develop robust clinical pathways to ensure their safe and efficient delivery. Given the limited experience of the Canadian medical oncology community with TCEs, collecting and publishing early clinical experiences with these novel agents will be essential to inform best practices and support their safe and effective adoption across the broader Canadian oncology community. The approval of tarlatamab, the first-in-class delta-like ligand 3 (DLL3)-targeted TCE for extensive-stage small cell lung cancer (ES-SCLC), underscores the importance of sharing early clinical experience with this agent, particularly given its unique safety profile, specific monitoring requirements, and use in a population that often has multiple comorbidities. Like other TCEs, tarlatamab is associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), adverse events (AEs) that necessitate the development of dedicated protocols by medical oncologists and multidisciplinary inpatient and outpatient clinical teams to ensure prompt recognition and management of these associated toxicities. By sharing insights into administration protocols, dose ramp-up procedures, post-cycle 1 monitoring, and AE management strategies implemented at their centres, early adopters of tarlatamab can help other institutions develop and refine their own protocols more efficiently. Lessons learned during the early implementation phase, including the roles of various healthcare providers and the transition from inpatient to outpatient care, should facilitate the smoother integration of tarlatamab and other TCEs for solid tumours into clinical pathways across Canada.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by high rates of recurrence, limited targeted treatment options, and frequent resistance to standard therapies. Dual-specificity protein phosphatase 1 (DUSP1), a stress-responsive regulator of mitogen-activated protein kinase (MAPK) signaling, has emerged as a context-dependent modulator of tumor progression and therapeutic response in TNBC. While reduced DUSP1 expression has been associated with aggressive tumor phenotypes and poor prognosis, accumulating evidence indicates that therapy-induced upregulation of DUSP1 can promote resistance to chemotherapy and radiotherapy by attenuating pro-apoptotic MAPK signaling and fostering immunosuppressive tumor microenvironment (TME). Emerging evidence highlights that DUSP1’s role is context-dependent on human cancers, including breast cancer (BC). This review synthesizes current evidence on DUSP1 biology in TNBC, with emphasis on its mechanistic involvement in chemotherapy resistance, radiation-induced immune modulation, and emerging implications for immunotherapy response.

Canadian real-world data (RWD) regarding palbociclib as a first-line therapy for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC) is limited. The PALbociclib CANadian (PALCAN) study examined palbociclib utilization patterns as first-line treatment for HR+/HER2− MBC using Alberta health administrative data. The final PALCAN cohort included 472 female patients with a median age of 64 years and a median follow-up time of 22.8 months (IQR: 0.7–88.2). The median (95% CI) duration of treatment was 13.8 (12.7–15.1) months in the overall cohort (IQR: 5.6, 24.8 months), and the probability of treatment discontinuation within the first year was 45%. Aromatase inhibitors (AIs) and fulvestrant were the accompanying endocrine therapies (ETs) in 83% (N = 393) and 14% (N = 64) (15 with unknown accompanying therapy) of patients, respectively. The median duration of treatment for patients receiving an AI as an accompanying therapy was 15.1 (13.6–17.4) months and 7.9 months (5.8–12.6) for patients receiving fulvestrant, which may suggest endocrine resistance in the latter group. The PALCAN data provides insights into practice patterns and the effectiveness of palbociclib as a first-line therapy in female patients with HR+/HER2− breast cancer in the Canadian real-world setting.