Back Back
HER2 ADCs: GU Malignancies

CME

Emerging HER2-Targeted Antibody–Drug Conjugates in Genitourinary Malignancies

Physicians: Maximum of 0.25 AMA PRA Category 1 Credit™

Released: April 08, 2024

Expiration: October 07, 2024

Elizabeth R. Plimack
Elizabeth R. Plimack, MD, MS, FASCO
CME/CE Information

Activity

Progress
1
Course Completed

Safety Profile Summary of Anti-HER2 ADC Payloads 

The toxicity profile for the ADCs discussed in this activity is mainly driven by the payload used: for T-DXd, the topoisomerase I inhibitor, and with disitamab vedotin, an MMAE—more taxane like. With T-DXd we can expect nausea, vomiting, diarrhea, and cytopenias (neutropenia and anemia). With disitamab vedotin we can expect alopecia, neuropathy, anemia, rash, and diarrhea. Key toxicities to watch for specifically with T-DXd are ILD/pneumonitis and ejection fraction decrease.20,22,25  

Download

Administration Considerations for ADCs in GU Tumors 

A critical next question is: how do HCPs manage the safety profile of these novel ADCs targeting HER2?   

The good news is that the safety profile is really driven by the payload, and the payload is chemotherapy, with deruxtecan being more topoisomeraselike and MMAE being more taxane-like.1   

We should routinely assess blood counts and test organ function with these therapies. In the table on the right, there are some recommendations for premedication and dose reductions, but I think it is the art of oncology here, and it is up to HCPs to work with their patients to best address AEs using the recommended dose holds, reductions, and discontinuations in the prescribing information.26    

Download

Managing ILD/Pneumonitis With T-DXd

What should HCPs do when they suspect ILD/Pneumonitis in a patient receiving T-DXd?   

In patients with suspected ILD/pneumonitis, we must hold the drug, assess symptoms, and use a CT scan for confirmation and/or involve a pulmonologist. The key is to rule out an alternate cause such as pneumonia (eg, with blood cultures, bronchoscopy). For confirmed ILD/pneumonitis of any grade, drug should be held and corticosteroids considered (prednisolone 0.5 mg/kg/day). The drug can be restarted if symptoms resolve within 28 days of onset. For those in whom ILD persists past 28 days, treatment should be done only with caution after full resolution and at a reduced dose. However, for grade 1 ILD that has not resolved within 49 days from last infusion, as well as for any grade 2-4 ILD, the drug must be discontinued and systemic corticosteroid treatment initiated promptly (eg, prednisolone ≥1 mg/kg/day or equivalent for ≥14 days, followed by taper for ≥4 weeks).26,27 

Download

Conclusions and Takeaways

It is still very early in this field of HER2-targeted ADCs for the treatment of GU tumors. The take-home message is that HCPs are going to be able to leverage IHC testing for HER2 into trial matching for patients going forward. Even now, many of these trials are enrolling, so I think if HCPs want to change 1 thing in their practices today, it would be to know the HER2 IHC status of their patient’s disease. Populating these trials would help investigators assess efficacy in larger cohorts of patients to further validate these preliminary findings. In particular, I am eager to know how these agents fare after chemotherapy and after EVP because that is a setting with limited options for patients.   

For more on the evolving status of HER2 testing and HER2-targeted ADCs in other malignancies including gastrointestinal and gynecologic cancers, visit the program page here.

Which of the following HER2 alterations is most frequently identified in patients with bladder cancer?

The phase II DESTINY-PanTumor02 trial evaluated trastuzumab deruxtecan (T-DXd) monotherapy in patients with advanced solid tumors not eligible for curative treatment and HER2+ expression. Which of the following efficacy results were reported for T-DXd in the GU patient population?

BACK | NEXT