Would you hold off using fam-trastuzumab deruxtecan-nxki in malignant pleural effusion?

No. While there may be a higher risk of higher-grade pulmonary adverse events in patients with pleural effusions, some of this is related to the impaired pulmonary function (e.g., loss of volume, lower flexibility of the lung tissue) and also the possible/probable involvement of intrapulmonary lymphatic spaces with tumor cells. In other words, the observed increase in higher-grade CT findings may be unrelated to T-DXd itself. These patients have inherently less pulmonary reserve. However, if T-DXd is the most active agent against the tumor, it is more likely to resolve these tumor-related issues. I would monitor with CT chest serially, monitor for O2 needs, cough, and other pulmonary symptoms, and correlate potential emerging signs and symp...

My decision on whether or not to use T-DXd in this situation would heavily depend on the patient's comorbidities, symptoms, and other radiographic findings. If the patient's dyspnea related to malignant pleural effusion is relieved with thoracentesis, she has no prior history of pulmonary disorders, and imaging is negative for ground-glass opacities, I would consider T-DXd given that this agent has superior anti-cancer activity to conventional chemotherapy and hence is most likely to produce a response leading to resolution or improvement of pleural effusions. I would monitor the patient closely for respiratory symptoms and with chest CT every 6 weeks early on in the treatment course.