Canadian Oncology Today

Current and Emerging Treatment Options for HER2‑Positive Gastroesophageal Cancer

2024-06-20T12:49:31+00:00

Gastroesophageal cancer (GEC) is the fifth most common cancer and the second most common cause of cancer-related mortality, with 1.3 million annual deaths worldwide. The global incidence is increasing, particularly among younger patients. GEC can be classified into subtypes based on anatomic location, histology, molecular characteristics, or tumour biology and genomics. In approximately 20% of all GECs overexpression of HER2 is identified. The landscape of treatment options in this patient population is evolving rapidly. This review summarizes the progress of HER2-directed therapies for advanced disease and highlights future directions in targeting the disease.

The epidermal growth factor receptor (EGFR) family of transmembrane tyrosine kinase receptors, EGFR/HER1, HER2/neu, HER3, and HER4, all have an extracellular ligand-binding domain, lipophilic transmembrane domain, and an intracellular domain with tyrosine kinase activity, binding to these receptors results in activation of downstream RAS/MAPK and PI3K/AKT pathways. In turn, this induces cell proliferation, differentiation, migration, and survival. The phase III Trastuzumab for Gastric Cancer (ToGA) trial reported the incidence of HER2-positive gastric cancer to be 22%. Therefore, targeting HER2 and its downstream signaling pathways holds important potential as a therapeutic strategy. Figure 1 illustrates potential targeting mechanisms that will be discussed in this review.

Current Uses and Pitfalls of Liquid Biopsy in NSCLC

2024-06-20T13:10:36+00:00

Liquid biopsy has emerged as an important tool in the diagnosis and management of lung and other cancers. Various analytes and analytical methods have been studied, including genomic testing by next-generation sequencing (NGS) and non-NGS approaches, including those examining methylation or DNA fragment size. Liquid biopsy, especially from plasma or blood, has several advantages over percutaneous or endoscopic tissue biopsy. It is less invasive, can be used serially for monitoring, and better reflects tumoural heterogeneity across metastatic sites, as opposed to a single area of the biopsied tumour. Herein, we highlight the current uses of liquid biopsy using circulating tumour DNA (ctDNA) analysis in routine clinical practice and potential pitfalls.

From Intractable to Treatable: Milestones and Horizons in the Management of HER2+ Breast Cancer

2024-06-20T13:18:08+00:00

The human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor (EGFR) family that initiates various signalling pathways that control cell proliferation and tumourigenesis. Historically, approximately 15% of breast cancers have been characterized by overexpression or amplification of HER2, known as “HER2+” breast cancers. This subtype has been associated with an adverse prognosis, along with a high risk of recurrence and worse survival outcomes. However, with the discovery and subsequent development of HER2‑targeted therapies, the clinical course of HER2+ breast cancers has fundamentally changed. Optimizing therapeutic strategies using existing and emerging HER2-targeted therapies to build upon these advances remains a major priority for clinical development and treatment delivery.

In 1998, the American Food and Drug Administration (FDA) and Health Canada approved trastuzumab, the first HER2-targeted therapy. Trastuzumab, a monoclonal antibody that binds to the HER2 receptor, has demonstrated clinical activity and improved outcomes in patients with metastatic HER2+ breast cancer when combined with chemotherapy. Following soon after, the first trial of adjuvant trastuzumab (HERA) demonstrated improvements in outcomes when combined with chemotherapy for early HER2+ breast cancer. More than 25 years after its first approval, trastuzumab retains a central role in the treatment of both early and advanced HER2+ breast cancer and has provided a backbone for both new therapeutic combinations (eg. with small molecule inhibitors of HER2) and new classes of therapeutic agents (antibody drug conjugates [ADC]). These successors of trastuzumab are currently redefining the HER2+ treatment landscape in both advanced and early breast cancer.

Survivorship Issues in Testicular Cancer

2024-06-20T13:41:57+00:00

Testicular cancer (TC) is the most prevalent tumor in young men aged 15–40 years, with an annual incidence of 3–11 new cases per 100,000 males in Western countries. In 2020, the International Agency for Research on Cancer reported 74,458 newly diagnosed cases of TC globally. The etiology of TC is complex and includes both genetic and environmental factors. The prognosis of TC is excellent with a >90% cure rate and a >95% 5-year survival rate with appropriate treatment. Treatments for TC include active surveillance, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, depending on the clinical stage and tumor subtype. It is crucial that patients receive information on the diagnosis, therapeutic management options, consequences of treatments, and surveillance protocols, which allows the patient to play an active role in the decision-making process. Fear of recurrence often affects TC survivors. Therefore, it is essential to fully involve the patient in the choice of the treatment to ensure an optimal compliance, especially when selecting the active surveillance strategy. In the modern era, in light of the excellent outcomes achieved in TC management, one of the high priorities is to deliver curative treatments while minimizing long-term toxicity. This focus can have a positive impact on quality of life and life expectancy of TC survivors.

An Evolving Paradigm in Borderline Resectable and Locally Advanced Pancreatic Cancer: Current Strategies and Opportunities for the Future

2024-06-20T13:54:13+00:00

Pancreatic ductal adenocarcinoma (PDAC), a cancer of the gastrointestinal tract, has been increasing in incidence, with an estimated doubling worldwide over the past two decades. Despite increases in awareness and innovations in genomics and drug discovery, 5-year survival remains low, at only 10%. This is in part owing to the majority of patients being diagnosed at the advanced stage of the disease, in addition to chemotherapy recalcitrant disease.

Surgical resection is necessary for a potential cure, however, this is only possible for the 10% of patients who present with resectable disease and potentially for those with borderline resectable disease. Locally advanced pancreatic cancer accounts for approximately 30% of those with PDAC and most of those patients are often precluded from curative intent surgery due to major vascular invasion and local infiltration into peri-pancreatic soft tissue. In cases of locally advanced disease, induction chemotherapy is often used, identifying the subgroup of patients more suited for local treatments and those who may later develop metastases. The treatment regimens used for patients with locally advanced PDAC are often extrapolated from trials involving patients with metastatic disease. In some cases, responses to neoadjuvant therapy have allowed for surgical resection, albeit these aggressive resections were associated with significant morbidity.

There is growing interest in identifying the optimal neoadjuvant treatment for patients with borderline resectable pancreatic cancer (BRPC) and locally advanced PDAC (LAPC) in an effort to improve outcomes. Here we review therapeutic strategies for borderline resectable and locally advanced PDAC, with a focus on novel systemic therapy regimens, chemoradiation, and different radiation modalities.