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A team of experts offered guidance for detecting and managing interstitial lung disease (ILD) in patients with HER2+ metastatic breast cancer treated with trastuzumab deruxtecan (T-DXd).

A recent pooled analysis of nine studies found the incidence of pneumonia/ILD was 15.4% in these patients. Most patients experienced grade 1 or 2 events, but a small proportion had grade 3-4 or fatal events, Hope Rugo, MD, of the University of California, San Francisco, and colleagues noted in a review in .

"Because specific guidelines are not available for patient selection, prophylaxis, screening, monitoring, and management of pneumonitis/ILD associated with HER2-targeted therapies, clinicians administering T-DXd can benefit from guidance on this topic," wrote Rugo and co-authors. The team included five oncologists, two oncology clinical pharmacists, and a pulmonologist with experience administering T-DXd.

The review covered five key strategies, known as the five "S" rules, including advice on screening, scanning for ILD, working synergistically with a care team, suspending cancer treatment, and managing ILD with steroids.

In the following interview, Rugo, who is director of Breast Oncology and Clinical Trials Education and medical director of Cancer Infusion Services at the University of California San Francisco, discussed aspects of each of these strategies in more detail.

For screening, you recommend clinicians consider pre–T-DXd testing, which should include high-resolution computed tomography (HRCT) of the chest. Should clinicians also consider pulmonary function tests (PFTs)?

Rugo: We really don't have any data on the value of PFTs in this setting. It's not clear that PFTs at baseline identify risk, and we have not used results to determine risk or steroid use. We do not recommend PFTs for baseline screening -- only for evaluation of symptoms.

You recommend all T-DXd-treated patients have HRCT scans at least every 12 weeks for the first year. Are there some patients who should have more frequent scans?

Rugo: Yes. The pooled analysis by Powell et al. () identified specific risk factors for ILD including renal insufficiency, longer time since metastatic diagnosis, baseline hypoxia, and being Japanese, among others. Increasing age also seems to increase risk somewhat. For this reason, I usually scan at 6 weeks for patients with risk factors, and for my older or sicker patients, particularly with treatment in later lines.

Do you have any advice for how best to coordinate care of patients with ILD with a pulmonologist?

Rugo: Patients with ILD requiring treatment can benefit from coordinated care with a pulmonologist specializing in interstitial lung disease, both for recommendations about treatment including steroid dosing and tapering, as well as evaluation of pulmonary function.

In addition, assistance regarding the differential diagnosis and work-up in patients presenting with symptomatic disease to ensure rapid and appropriate treatment may be critical in specific cases. For these reasons, consulting a pulmonologist early after diagnosis is recommended for symptomatic ILD.

You recommend suspension of T-DXd treatment and systemic corticosteroids if pneumonia/ILD is detected. How do your recommendations for this treatment and follow-up differ by grade of ILD?

Rugo: Patients with asymptomatic, grade 1 ground glass opacities or consolidation should have treatment held until resolution of radiographic findings on high resolution non-contrast chest CT scan. To speed recovery, and allow re-challenge with T-DXd within a reasonable time period, we recommend instituting prednisone at 0.5 mg/kg/d with carefully monitoring, then tapering the steroids after recovery.

For patients with symptomatic ILD, prednisone at a dose of 1 mg/kg/day should be promptly instituted, and consultation with a specialized pulmonologist should obtained. Early diagnosis and treatment are critical to avoid progression to higher-grade pneumonitis.

Regular pulmonary imaging is important, as diagnosis and treatment of asymptomatic ILD can avoid progression to symptomatic disease.

Finally, what are the treatment options for patients who have steroid-refractory ILD?

Rugo: For steroid refractory ILD, consultation and collaboration with a pulmonary specialist and intensivist should be promptly obtained to assist in determination of appropriate additional immunosuppressive therapies.

Read the review here and expert commentary about it here.