New Oncology Guidelines Worth Reading

Recently, three new guidelines related to oncology have been issued by major European and American medical associations to help clinicians provide the best care for an individual patient with a specific condition related to either their cancer or toxicity of cancer treatment. Additionally, a commentary on bone health and denosumab discontinuation in cancer patients increases awareness regarding the associated risks, including the “rebound” phenomenon and multiple vertebral fractures.

  • ESC Guideline on Cardio-Oncology. The European Society of Cardiology (ESC), in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO), and the International Cardio-Oncology Society (IC-OS), recently issued the first guideline on cardio-oncology. The guideline, which contain 272 recommendations, discusses the definitions, diagnosis, treatment, and prevention of cancer therapy-related cardiovascular toxicity (CTR-CVT), as well as the management of cardiovascular disease (CVD) caused directly or indirectly by cancer. To provide the best possible cancer treatment safely to patients, and to minimize CTR-CVT across the entire continuum of cancer care requires a broad knowledge of cardiology, oncology, and hematology; thus, interdisciplinary collaboration and communication is key. The guideline recommends a personalized approach, with consideration of the baseline CV toxicity risk in treatment decision-making. Prevention strategies and monitoring of CV toxicity during specific cancer treatments (e.g. chemotherapy, HER2-targeted therapy, tyrosine kinase inhibitors, endocrine therapies, immunotherapies, hematopoietic stem cell transplantation, and radiotherapy), and in special populations (e.g. pregnant patients, cardiac tumors, amyloid light-chain cardiac amyloidosis, implantable electronic devices) are discussed. It also provides guidance for long-term follow-up and assessment of chronic CV complications in cancer survivors. In addition, the importance of patient education and counseling is highlighted. Eur Heart J. 26 August 2022 [Epub ahead of print].

  • New ESMO Guideline on Managing Immunotherapy Toxicities. The new guideline from the European Society for Medical Oncology (ESMO), written by a multidisciplinary group of experts from Europe, Australia, and the US, provides updated recommendations for managing immunotherapy-related toxicity, based on available scientific evidence and the authors’ expert opinions. The guideline covers the assessment, diagnosis, and treatment of the most common immunotherapy-related adverse events (irAEs), considering grade and type of irAEs. In general, the management of irAEs consists of four sequential steps, including: the diagnosis and grading of irAEs; ruling out differential diagnoses and pre-immunosuppression work-up; selecting an appropriate immunosuppression strategy for grade ≥2 events; and active evaluation at 72 hours to adapt treatment as needed. Corticosteroids (CSs) play a crucial role in the management of irAEs; however, these agents may also cause AEs. Thus, to minimize these, the guideline recommends prescribing the lowest effective CS dose for the shortest possible time, which is likely to be several weeks (including tapering) for grade ≥3 irAEs. CS therapy should be tapered or discontinued only on medical advice, and lifestyle adaptations should be taken to minimize the risk of CS-induced AEs. Some cancer patients with CS-refractory irAEs may benefit from cytokine inhibitors. Other immune-modulating agents are also sometimes used, based on extrapolation from their application in autoimmune diseases, but there is a lack of evidence from prospective studies in the management of irAEs. The guideline also discusses in detail the management of various irAEs, including skin toxicities, endocrinopathies, hepatotoxicities, cholangitis, pancreatic toxicities, gastrointestinal toxicities, pulmonary toxicities, rheumatologic toxicities, neurologic toxicities, cardiovascular toxicities, renal toxicities, ocular toxicities, and hematological toxicities. In addition, the authors highlight that a decision on rechallenge of immunotherapy in patients who have previously developed ≥3 irAEs depends on multiple factors and needs to be discussed by a multidisciplinary team for each individual patient. Ann Oncol. 2 October 2022 [Epub ahead of print].

  • Updated ASCO Guideline on Treating Metastatic Colorectal Cancer. The new guideline from the American Society of Clinical Oncology (ASCO) provides recommendations, based on seven important clinical questions, related to the management of patients with metastatic colorectal cancer (mCRC). Doublet chemotherapy (FOLFOX and FOLFIRI) is the recommended chemotherapy backbone for patients with previously untreated, initially unresectable microsatellite stable (MSS) or proficient mismatch repair (pMMR) mCRC; triplet chemotherapy may also be offered for selected patients, although the higher incidence of ≥3 irAEs with triplet chemotherapy should be taking into account. Chemotherapy should be given in combination with an anti-vascular endothelial growth factor (anti-VEGF). However, for left-sided, MSS/pMMR, RAS wild-type mCRC, chemotherapy doublet plus anti-epidermal growth factor receptor therapy (anti-EGFR) is the preferred first-line option. For patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) mCRC tumors, pembrolizumab is the recommended first-line treatment choice. After progression on at least one previous line of therapy, for patients harboring BRAF V600E-mutant mCRC, the guideline recommends encorafenib plus cetuximab. Cytoreductive surgery and systemic chemotherapy may be offered to selected patients with colorectal peritoneal metastases; however, the addition of oxaliplatin-based hyperthermic intraperitoneal chemotherapy is not recommended. Stereotactic body radiation therapy may be used after systemic therapy for patients with liver oligometastases who are not candidates for resection. Patients with mCRC who are candidates for potentially curative resection of liver metastases should be treated with surgery with or without perioperative chemotherapy. The guideline also formally endorses multidisciplinary team management and shared decision-making. In addition, it highlights the importance of offering patients the option of participating in a clinical trial. J Clin Oncol. 17 October 2022 [Epub ahead of print].

  • Risks of Denosumab Discontinuation in Cancer Patients. The anti-RANKL monoclonal antibody, denosumab, is approved for the management of patients with solid tumors and bone metastases, and for the prevention of bone loss and/or fragility fractures associated with endocrine therapies such as androgen deprivation therapy (ADT) for prostate cancer or aromatase inhibitors for breast cancer. However, based on its mechanism of action, discontinuation of denosumab leads to a “rebound” phenomenon, which has been associated with a significant compromise in bone structure and may clinically present as multiple vertebral fractures. In a commentary published recently in Oncologist, the authors highlight that more awareness is needed among oncologists regarding the risks of denosumab discontinuation and provides the evidence for various bone health agents that may mitigate the rebound phenomenon. The authors recommend avoiding denosumab discontinuation in patients who have been treated with more than two doses of denosumab. However, if cessation is needed, they recommend using transition regimens (e.g. zoledronate, alendronate) based on guidelines from a non-cancer patient population with osteoporosis. Oncologist. 17 October 2022 [Epub ahead of print].