Ask AI
Back Back
ADC AEs in Breast/Lung Cancer
Expert Perspectives and Insights on ADC-Associated Adverse Events in Patients With Breast and Lung Cancers

Released: December 29, 2025

Julia LaBarbera
Julia LaBarbera, MSN, RN, AGACNP-BC
Beth Sandy
Beth Sandy, MSN, CRNP, FAPO
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Patients receiving trastuzumab deruxtecan, which is now approved as first-line therapy with pertuzumab for HER2-positive MBC, need to be educated about symptoms of ILD/pneumonitis.
  • Stomatitis associated with datopotamab deruxtecan can be managed with the use of prophylactic steroid mouthwash and, during infusion, cryotherapy.
  • Supportive care must be individualized based on the specific ADC and patient characteristics. Proactive, standardized prevention strategies improve tolerability and help patients remain on effective treatment.

The adoption of antibody–drug conjugates (ADCs) in breast and lung cancer is nothing short of transformative. The ADCs are also now showing good treatment options for patients with non-small-cell lung cancer (NSCLC) who harbor particular biomarkers such as HER2, EGFR, and MET overexpression. These therapies allow us to target tumors with an unprecedented degree of precision, but they also introduce a new layer of complexity, particularly when it comes to adverse event (AE) management. As advanced practice providers, we hear about AEs early on and ultimately guide our patients through managing them. At the JADPRO Live 2025 meeting, we had the opportunity to speak on this very topic—focusing on HER2- and TROP2-directed ADCs in breast cancer and lung cancer—and to engage in a rich question and answer session with colleagues who, like us, are on the frontlines of patient care.

Understanding the Nuance of ADCs

Julia LaBarbera, MSN, RN, AGACNP-BC:
ADCs are not your standard antitumor therapy. Each is composed of 3 components: a monoclonal antibody, a linker, and a potent cytotoxic payload. What sets them apart is the delivery mechanism and the so-called bystander effect. Once the ADC binds to its target on the tumor cell and is internalized, the cytotoxic drug is released, not only killing the target cell but, in many cases, diffusing into the surrounding microenvironment to kill neighboring cells. This mechanism allows ADCs to work even when only a portion of tumor cells express the target antigen, which is a game-changer in settings like HER2-low or TROP2-expressing breast cancers.

But although the efficacy is compelling, the potential for serious toxicity cannot be minimized. Each ADC comes with its own toxicity profile, and understanding these differences is crucial to patient safety.

Trastuzumab Deruxtecan: Potent and Effective, but Watch the Lungs

Julia LaBarbera, MSN, RN, AGACNP-BC:
Trastuzumab deruxtecan (T-DXd) has rapidly moved into earlier lines of treatment in HER2-positive metastatic breast cancer based on impressive data from trials such as DESTINY-Breast03 and, more recently, DESTINY-Breast09. The latter showed a median progression-free survival of 40.7 months when T-DXd was used in combination with pertuzumab improving upon traditional first-line regimens such as taxane/trastuzumab/pertuzumab, which has been the standard of care for more than a decade. This ultimately led to its approval by the FDA. We also see its use growing in HER2-low and even HER2-ultralow advanced breast cancer, based on consistent benefit across these subtypes.

However, these benefits come with significant risks, the most worrisome being interstitial lung disease (ILD) and pneumonitis. These toxicities can be easily missed and need to monitored for closely.

Education is the first step toward prevention. Patients need to know that symptoms like shortness of breath or a new cough warrant immediate evaluation. In my practice, I follow what I call the “5 S’s”: screen at baseline, scan promptly with high-resolution imaging if symptoms occur, assess for synergistic risk factors (like preexisting lung disease or metastases), suspend treatment immediately with any suspicion of ILD, and start steroids early and appropriately for the patient’s condition.

TROP2 ADCs: Tailoring Supportive Care to the Agent

Julia LaBarbera, MSN, RN, AGACNP-BC:
In addition to HER2-targeting ADCs, we are seeing increasing use of TROP2-directed ADCs, namely sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd). Both are effective in hormone receptor–positive, HER2-negative metastatic breast cancer and triple-negative breast cancer, although their toxicity profiles are notably distinct.

With SG, my primary concerns are gastrointestinal and hematologic AEs. Nausea is common and often delayed, and I typically use a 3- to 4-drug antiemetic regimen, with additional medication provided for home use. Diarrhea can also be significant, as can neutropenia, especially in patients with the UGT1A1*28 polymorphism, which may impair drug metabolism. We do not routinely test for this genotype up front, but we do consider it when patients experience unexpected or prolonged toxicity.

Beth Sandy, MSN, CRNP, FAPO:
Dato-DXd presents a different set of challenges, most notably stomatitis and ocular toxicity. In fact, stomatitis was the most frequent and burdensome AE reported in pooled analysis of TROPION-Lung studies, and we have seen this reflected in the clinic. What has become clear is that prevention is key. I prescribe a compounded dexamethasone mouthwash (0.1 mg/mL) to be used 4 times daily starting with the first cycle; do not wait until after symptoms appear. I also encourage cryotherapy, such as ice chips held in the mouth during infusion to minimize drug delivery to the oral mucosa. It is not the most comfortable strategy, but it can be effective. There are newer cryogenic mouthpieces on the market, and if patients are able to obtain these devices, they can be useful.

For ocular toxicity, which most commonly presents as dry or irritated eyes, I recommend preservative-free artificial tears 4 times daily beginning on Day 1 of treatment. We also discourage contact lens use during therapy, which can be inconvenient for patients but important for symptom control. Although ocular toxicity has not been a major issue in my practice so far, my colleagues report variable experiences, which suggests prevention protocols are worth standardizing.

Telisotuzumab vedotin (Teliso-V) is approved for use in metastatic nonsquamous NSCLC with high c-MET expression (IHC 3+) targeting c-MET overexpression identified by immunohistochemistry, not MET exon 14 skipping mutations. In the LUMINOSITY study, Teliso-V demonstrated clinically meaningful activity in this biomarker-defined population, with peripheral neuropathy and edema as key toxicities requiring monitoring.

Question and Answer Insights: Clinical Pearls for the Audience

Beth Sandy, MSN, CRNP, FAPO:
Our audience at JADPRO asked some excellent questions that highlight the real-world challenges advanced practice professionals face. One important question was what the optimal timing and implementation of biomarker testing for HER2 and c-MET is by immunohistochemistry. Although technically feasible on archival tissue, I generally recommend rebiopsy at the time of NSCLC progression, as expression can change during the course of treatment and both T-DXd and Teliso-V are approved for previously treated patients with advanced NSCLC and those 2 biomarkers. This is especially important in ADCs that rely on overexpression, as opposed to genetic mutations.

Another attendee asked whether steroids or cryotherapy were used preventively with Dato-DXd in the TROPION trials. They were not used consistently, which likely contributed to the high incidence of stomatitis. It has become clear post approval that preventive steroid mouthwash should be standard in this setting.

Finally, we were asked about newer cryotherapy devices beyond ice chips. One innovative example is a cooling mouthguard-like device that can be frozen and worn during infusion. Although not yet in widespread use, it represents an exciting avenue for supportive care innovation.

Your Thoughts
What has your experience been with ADCs while treating patients with advanced breast cancer and NSCLC?  Which ADC-related AEs are the greatest challenges for you or your patients? Please answer the polling question or leave a comment to join the discussion. 

Continue

Poll

1.

Which of the following ADC-related AEs do your patients tell you is most worrisome to them?

Submit