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HER2 Targeted ADCs: GI Cancers

CME

Emerging HER2-Targeted Antibody Drug Conjugates in Gastrointestinal Malignancies

Physicians: Maximum of 0.75 AMA PRA Category 1 Credit™

Released: April 09, 2024

Expiration: October 08, 2024

Zev A. Wainberg
Zev A. Wainberg, MD
CME/CE Information

Activity

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Course Completed

Management of ILD Associated With T-DXd

As I previously alluded to, ILD/pneumonitis is an important consideration with the use of T-DXd for the management of GI cancers.38 We must closely monitor for signs and symptoms of ILD/pneumonitis, as well as routinely assess blood counts and organ function tests with ADC therapy.

In patients with suspected ILD/pneumonitis, however, we must hold the drug, assess symptoms, and use a CT scan for confirmation and/or involve a pulmonologist as appropriate. The key is to rule out an alternate cause such as pneumonia (eg, with blood cultures, bronchoscopy).

Regarding management of confirmed ILD/pneumonitis of any grade, drug should be held and corticosteroids considered (prednisolone 0.5 mg/kg/day). T-DXd can be restarted if symptoms resolve within ≤28 days from onset. For those in whom ILD/pneumonitis persists past 28 days from onset, treatment should be done only with caution after full resolution and at a reduced dose. However, if grade 1 ILD/pneumonitis has not resolved within 49 days from last infusion, as well as for any grade 2-4 ILD (eg, radiologic findings), we must discontinue the drug and promptly initiate systemic corticosteroid treatment (eg, prednisolone ≥1 mg/kg/day or equivalent for ≥14 days, followed by taper for ≥4 weeks).

Fortunately, a grading system has been well established for ILD/pneumonitis and offers clear guidance as to how to approach each patient.

Underlying conditions affecting risks remain unclear, but certainly patients who have baseline lung comorbidities may be at higher risk.

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Risk Factors for ILD With T-DXd: Pooled Analysis

The risk factors for developing ILD have been described in the literature for numerous cancers but ultimately remain unclear. However, patients who have baseline lung comorbidities may be at higher risk for developing ILD/pneumonitis with T-DXd.63-65

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Go Online for More

To learn more about the role of HER2 and HER2 ADCs, specifically in GI cancers, visit the program page for this activity. Online you will find free downloadable slides; an expert-authored commentary summarizing current HER2 testing in genitourinary, GI, and gynecologic cancers; and a synopsis of the latest clinical data. You also will find other CME-certified expert-led education on anti-HER2 ADCs in genitourinary and gynecologic cancers.

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Your patient is receiving trastuzumab deruxtecan (T-DXd) as second-line therapy for advanced/recurrent HER2-positive GEJ adenocarcinoma and begins to develop what appears to be symptomatic grade 1 interstitial lung disease (ILD)/pneumonitis. What would be the most appropriate management strategy?

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