From the Guidelines
Trastuzumab can cause fatal pulmonary toxicity, including interstitial lung disease (ILD) and pneumonitis, which requires active surveillance and proper management, as stated in the 2020 ESMO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) 1.
Pulmonary Complications of Trastuzumab
Trastuzumab is associated with pulmonary complications, including ILD and pneumonitis, which can be fatal. The incidence of ILD/pneumonitis is approximately 13.6% with trastuzumab deruxtecan, a compound composed of trastuzumab, with a fatal risk of 2.2% 1.
Management of Pulmonary Complications
If a patient develops respiratory symptoms while on trastuzumab, treatment should be temporarily suspended, and prompt evaluation with chest imaging and pulmonary function tests should be performed. For mild cases, trastuzumab may be resumed after symptoms resolve, but in moderate to severe cases, permanent discontinuation is recommended along with corticosteroid therapy.
Risk Factors and Monitoring
Risk factors for pulmonary complications include prior or concurrent radiation therapy, pre-existing lung disease, and combination therapy with taxanes or other chemotherapeutic agents. Regular monitoring of respiratory symptoms and baseline pulmonary function assessment before initiating therapy are recommended for early detection and management of these complications.
- Key points to consider:
- Active surveillance and proper management of pulmonary toxicity are crucial when using trastuzumab.
- Combination therapy with other chemotherapeutic agents may increase the risk of pulmonary complications.
- Regular monitoring of respiratory symptoms and baseline pulmonary function assessment are essential for early detection and management of pulmonary complications, as recommended by the ESMO-ESMO international consensus guidelines for advanced breast cancer (ABC 5) 1.
From the FDA Drug Label
Trastuzumab product use can result in serious and fatal pulmonary toxicity. Pulmonary toxicity includes dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, non-cardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, and pulmonary fibrosis. Such events can occur as sequelae of infusion reactions [see Warnings and Precautions (5. 2)]. Patients with symptomatic intrinsic lung disease or with extensive tumor involvement of the lungs, resulting in dyspnea at rest, appear to have more severe toxicity.
Pulmonary Complications of Trastuzumab:
- Trastuzumab can cause serious and fatal pulmonary toxicity.
- Pulmonary toxicity may include:
- Dyspnea
- Interstitial pneumonitis
- Pulmonary infiltrates
- Pleural effusions
- Non-cardiogenic pulmonary edema
- Pulmonary insufficiency and hypoxia
- Acute respiratory distress syndrome
- Pulmonary fibrosis
- These events can occur as a result of infusion reactions.
- Patients with pre-existing lung disease or extensive tumor involvement in the lungs may be at higher risk for severe pulmonary toxicity 2.
From the Research
Trastuzumab Pulmonary Complications
- Trastuzumab deruxtecan (T-DXd) has been associated with an increased risk of lung toxicity, including interstitial lung disease (ILD) and pneumonitis 3.
- The overall incidence of all-grade ILD/pneumonitis cases was 11.40% in a systematic review of 14 studies with a total of 1193 patients 3.
- Grading of the adjudicated T-DXd-induced ILD/pneumonitis was reported in 122 patients, with the majority of the cases (78.69%) occurring as grade 1 or 2 3.
- Death was reported in 13 out of 122 (10.66%) patients with T-DXd-induced ILD/pneumonitis 3.
- Computed tomography (CT) patterns of T-DXd-related pneumonitis can guide diagnosis and management, with the most common pattern being cryptogenic organizing pneumonia (COP) 4.
- The COP pattern was observed in 65 patients (72%), followed by a newly identified COP/hypersensitivity pneumonitis (HP) pattern (13%), acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) pattern (11%), and HP pattern (3%) 4.
- CT patterns were associated with Common Terminology Criteria for Adverse Events severity grades of pneumonitis, with the AIP/ARDS pattern having higher grades compared with others 4.
- Prior treatment with abemaciclib may be a risk factor for T-DXd pneumonitis, while pre-treatment chest imaging abnormalities, prior immune checkpoint inhibitor treatment, and prior chest or breast radiation did not increase the risk of T-DXd pneumonitis 5.
- Interstitial pneumonitis has been reported in patients treated with trastuzumab emtansine, highlighting the need for careful monitoring and management of pulmonary complications 6, 7.