The approval of CDK4/6 inhibitors has dramatically improved care for the treatment of HR+/HER2– advanced breast cancer, but navigating the rapidly-expanding treatment evidence base is challenging. In this narrative review, we provide best-practice recommendations for the first-line treatment of HR+/HER2– advanced breast cancer in Canada based on relevant literature, clinical guidelines, and our own clinical experience. Due to statistically significant improvements in overall survival and progression-free survival, ribociclib + aromatase inhibitor is our preferred first-line treatment for de novo advanced disease or relapse ≥12 months after completion of adjuvant endocrine therapy and ribociclib or abemaciclib + fulvestrant is our preferred first-line treatment for patients experiencing early relapse. Abemaciclib or palbociclib may be used when alternatives to ribociclib are needed, and endocrine therapy can be used alone in the case of contraindication to CDK4/6 inhibitors or limited life expectancy. Considerations for special populations—including frail and fit elderly patients, as well as those with visceral disease, brain metastases, and oligometastatic disease—are also explored. For monitoring, we recommend an approach across CDK4/6 inhibitors. For mutational testing, we recommend routinely performing ER/PR/HER2 testing to confirm the subtype of advanced disease at the time of progression and to consider ESR1 and PIK3CA testing for select patients. Where possible, engage a multidisciplinary care team to apply evidence in a patient-centric manner.

Practice and behaviour change in healthcare is complex, and requires a set of critical steps that would be needed to implement and sustain the change. Neoadjuvant chemotherapy for breast cancer is traditionally used for locally advanced disease and is primarily advantageous for surgical downstaging purposes. However, it does also offer patients with certain biologic subtypes such as the triple negative or Her2 positive breast cancers the opportunity to improve survival, even in early stage disease. During the height of the pandemic, an opportunity and motivation for the increased use of neoadjuvant therapy in breast cancer was identified. This paper describes the conditions that have supported this practice change at the provider and institutional levels. We also include our own institutional algorithm based on tumor biology and extent of disease that have guided our decisions on breast cancer management during the pandemic. Our processes can be adapted by other institutions and breast oncology practices in accordance with local conditions and resources, during and beyond the pandemic.

The results of the Phase III DESTINY-Breast04 trial of trastuzumab deruxtecan (T-DXd) are leading to a shift in both the classification and treatment of human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer. In this trial, T-DXd was associated with a substantial survival benefit among patients with hormone receptor-positive and hormone receptor-negative disease and low expression of HER2, a biomarker previously considered unactionable in this treatment setting. Herein, we discuss the evolving therapeutic pathway for HER2-low disease, ongoing clinical trials, and the potential challenges and evidence gaps arising with treatment of this patient population.

Canada has one of the most complex and rigorous drug approval and public reimbursement processes and is, unfortunately, one of the countries with the longest delays in drug access. To assess the overall impact of systemic delays in access to cancer therapy, a targeted literature review (TLR) was performed to identify studies associated with the clinical, economic, and quality of life impacts of delayed access to oncology drugs. Using MEDLINE/PubMed databases and snowballing, four unique records met the eligibility criteria. Results revealed that clinical outcomes were the most impacted by systemic delays in access to oncology drugs (e.g., life years lost, overall survival, and progression-free survival). The four articles retrieved by the TLR specifically illustrated that a substantial number of life years could potentially be saved by increasing systemic efficiency regarding the development, approval, and reimbursement processes of new drugs for advanced malignancies. It is imperative that initiatives are put in place to improve the performance and speed of Canadian drug regulatory and health technology assessment (HTA) processes, especially for new cancer therapeutics. The proposed solutions in this paper include better coordination between HTA and Canadian payers to harmonize coverage decisions, international collaborations, information sharing, and national standards for timeliness in oncology drug access.

Postmenopausal patients with hormone-sensitive early breast cancer are typically treated with adjuvant endocrine therapy, which significantly reduces the risk of recurrence. Because treatment is of a long duration, side effects from adjuvant therapy can be problematic. The aromatase inhibitors (AIs) are replacing tamoxifen as first-line treatment agents for early breast cancer. Here, we present the side-effect data associated with AIs in relation to bone, gynecologic, and cardiovascular health and to arthralgia and myalgia. Although AIs have been shown to decrease bone density, increase arthralgia, and affect vaginal health, these adverse events are usually manageable, and several strategies can be followed to improve quality of life in women on AI treatment. To optimize adherence to therapy. It is important that these issues are addressed so that women can benefit from treatment.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.