Table 1.

Asia-Pacific multidisciplinary panel recommendations for the monitoring and management of T-DXd–related adverse events in patients with metastatic breast cancer

Adverse event	Recommendations
ILD/pneumonitis	Prior to T-DXd treatment	Eligibility for T-DXd should be carefully evaluated by performing a chest CT scan and confirming that the patient has no current, suspected, or prior history of ILD/pneumonitis or significant pulmonary disease
		Patients should be educated on the signs and symptoms of ILD/pneumonitis and encouraged to seek medical attention and promptly report events suggestive of ILD/pneumonitisa
	Monitoring	Patients should undergo regular CT scans of the thorax (standard or high-resolution non-contrast CT), but the frequency of CT assessments may have to account for the median time of ILD/pneumonitis onset (median [range] 5.6 (1.1–20.8) months) [47], reimbursement, practicality, or accessibilityb
		Pulse oximetry or exertional pulse oximetry walk tests may be performed at each visit to augment ILD/pneumonitis monitoring, although their sensitivity and specificity for the detection of ILD/pneumonitis are unknown
		Baseline PFTs prior to T-DXd treatment may not be recommended for patients who appear to have normal lung function, due to resource burden, cross infection potential (e.g., SARS-CoV-2), and patient inconvenience
	Diagnosis	In patients with incipient pulmonary symptoms or abnormal radiological findings, T-DXd–induced ILD/pneumonitis should be differentially diagnosed from infective causes or other aetiologies with consultations with at least one supporting specialist, such as a pulmonologist, a radiologist, or an infectious disease specialist
		High-resolution chest CT should be the principal tool for diagnosing ILD/pneumonitis
		Bronchoscopy and BAL could be considered for patients who are febrile, experience atypical radiographic patterns, or have severe ILD/pneumonitis requiring hospitalisation despite steroid initiation
	Management	It must be emphasised that the dose of steroids and length of tapering is variable according to the grade of severity, and that physicians should refer to guidelines (i.e., Swain et al 2022 [28] and Conte et al 2022 [53]) For Grade 1 ILD/pneumonitis, interrupt T-DXd, consider initiating corticosteroids (e.g., ≥ 0.5 mg/kg/day prednisolone or equivalent) to treat and prevent the risk of progression, and start empiric anti-infectives if infective aetiology is not entirely excluded
		For patients with a repeated incident of Grade 1 ILD/pneumonitis, follow Grade 1 management strategies: withholding T-DXd until resolution to Grade 0 and initiating systemic corticosteroids and/or empiric anti-infectives. T-DXd rechallenge may require an evaluation of factors such as response to T-DXd and eligibility for other therapies
		For Grade ≥2 ILD/pneumonitis, permanently discontinue T-DXd and promptly initiate systemic steroids for > 14 days or until complete resolution of clinical and chest CT findings, followed by a gradual taper over ≥ 4 weeksc,d
Nausea and vomiting	Prophylaxis with serotonin (5-HT3) receptor antagonists and dexamethasone (with or without neurokinin-1 receptor antagonist) should be considered for the management of nausea and vomiting associated with T-DXd
	Managing severe or breakthrough nausea and vomiting may require the addition of neurokinin-1 receptor antagonists (and olanzapine, if indicated) to the antiemetic regimen
	Low-dose olanzapine (5 mg) could be offered to patients who experience delayed nausea, but treatment duration might need to be proactively optimised to curtail side effects
	For patients with acceptable emesis control, consider either providing dexamethasone for 1 day (on day of treatment) or omitting it
Neutropenia	Primary G-CSF prophylaxis may not be necessary for most patients commencing T-DXd, but risk factors including the number of prior lines of therapy, history of neutropenia, and febrile neutropenia may need to be considered
	Secondary G-CSF prophylaxis to prevent cycle delays or dose reduction could be considered for patients who have experienced recurring Grade 3 neutropenia
Anaemia	CBC with differential may be considered at each visit to screen for anaemia, and a complete workup is recommended upon signs and symptoms of anaemia
	Dose delay and/or reduction are recommended for managing Grade ≥ 3 anaemia, and iron therapy (oral or IV) or blood transfusions should be considered, if clinically indicated
Thrombocytopenia	Dose delay and/or reduction are recommended for managing Grade ≥ 3 thrombocytopenia, and supportive platelet transfusion should be considered, if clinically indicated
Fatigue	Health care professionals should be vigilant for treatable causes of fatigue (e.g., anaemia). They can encourage patients to use support groups and practice low-intensity exercises, as well as empower patients’ caregivers
Alopecia	To increase treatment acceptance, patients should be made aware of the risk of alopecia prior to starting T-DXd
	Scalp cooling could be considered but its efficacy in patients on T-DXd is unknown
Cardiac	ESC guidelines recommend that patients on anti-HER2 therapy should have an echocardiography at baseline and be repeated every 3 months during the first year [127]. However, for asymptomatic and low risk patients (i.e., without hypertension, borderline low LVEF, or received anthracyclines), surveillance can be reduced to every 6 months during future treatment. In high-risk patients, more frequent echocardiography and cardio-biomarkers may be considered Cardiac magnetic resonance imaging should be considered when echocardiography is unavailable or non-diagnostic

BAL bronchoalveolar lavage, CBC complete blood count, CMV cytomegalovirus, CT computed tomography, G-CSF granulocyte colony-stimulating factor, ESC European Cardiology Society, ILD interstitial lung disease, IV intravenous, LVEF left ventricular ejection fraction, PFT pulmonary function test, SARS-CoV-2 severe acute respiratory syndrome coronavirus 2, T-DXd trastuzumab deruxtecan

^aSigns and symptoms of ILD/pneumonitis may include dyspnoea with exertion, cough, fever and other new or worsening respiratory symptoms

^bFor instance, 6-weekly CT scans may be considered for the first 6–12 months of T-DXd treatment given the known median time of ILD/pneumonitis onset and clinical trial experience. If longer intervals are chosen (9- or 12-weekly) other supplemental strategies to monitor for ILD/pneumonitis are recommended

^ce.g., 1 mg/kg prednisone or equivalent for Grade 2, or 500–1000 mg/day empirical high-dose methylprednisolone IV for 3 days followed by 1 mg/kg prednisone or equivalent for > 14 days for Grade 3/4

^dWhile on high-dose systemic corticosteroids (particularly pulse steroids), consider adding Pneumocystis jirovecii pneumonia prophylaxis (e.g., co-trimoxazole) and performing surveillance for CMV (e.g., CMV pp65 antigen)