Proactive, Multidisciplinary AE Management Enables Safer, Sustained ADC Use in Breast and Lung Cancers

The rise of antibody-drug conjugates (ADCs) as highly effective agents for the treatment of breast and lung cancers has been accompanied by a need to carefully weigh the benefits of this drug class against its potential risks. Detailed organ monitoring, individualized patient education, prophylactic management strategies, and coordinated specialty care must converge to sustain the safe delivery of ADCs.

“[By knowing] how to prevent, monitor, and treat these toxicities, we're going to be able to provide our patients with better therapy, and that's the most important part of our discussion today,” Hope S. Rugo, MD, FASCO, said during a recent OncLive Peer Exchange. “We want to help patients live as long as possible with their best quality of life [QOL].”

During the panel discussion, multidisciplinary breast and lung cancer experts gathered to discuss comprehensive strategies for identifying and mitigating the diverse adverse effects (AEs) associated with ADCs. The conversation narrowed on fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and datopotamab deruxtecan-dlnk (Dato-DXd; Datroway); both are FDA approved for various indications across the lung and breast cancer treatment continuums.

How do baseline lung assessments and pneumonitis prevention strategies increase patient safety and treatment adherence during ADC treatment?

The panelists first delved into the identification and management of interstitial lung disease (ILD)/pneumonitis, which has been associated with ADCs approved in lung and breast cancer settings. For instance, the prescribing information for both T-DXd and Dato-DXd features warnings for ILD and pneumonitis, noting that fatal cases have been reported with the use of these agents.^1,2 The black box warning for T-DXd–associated ILD emphasizes that health care practitioners should monitor for and promptly investigate respiratory symptoms, as well as other symptoms such as fever.¹ Physicians are also advised to permanently discontinue these ADCs in all patients with grade 2 or higher ILD/pneumonitis.

The warnings and precautions for ILD in the Dato-DXd prescribing information state that if ILD/pneumonitis is suspected, the drug should be withheld and corticosteroids initiated.² Additionally, providers should permanently discontinue the agent in patients with confirmed grade 2 or higher ILD/pneumonitis.

Aaron Lisberg, MD, opened the discussion by focusing on lung cancer, stating that many thoracic oncologists are already familiar with identifying and managing ILD since this toxicity is also associated with immune checkpoint inhibitors.

“It’s important to identify past history; does the patient have a history of pneumonitis that required steroid use?” he said. “Do they have findings [that are] concerning for pneumonitis or ILD on the baseline scan? Those are the key questions to be asking. There are other known risk factors for ILD, but none of those have been clearly validated at a high level [in breast and lung cancers], so I don't think there’s anything in a patient's history beyond pneumonitis requiring steroids or ILD on baseline scans that would exclude them from therapy [with ADCs]. However, certain [factors], such as significant smoking history or prior lung issues, can be concerning.”

Rugo added that ILD risk in breast cancer increases with age and the number of prior lines of treatment. The experts noted the importance of facilitating open, direct communication with patients to provide them with opportunities to disclose any new or worsening respiratory symptoms. They emphasized that the presence of heightened symptoms of this nature calls for immediate evaluation by a pulmonary team and treatment pauses until drug-related toxicity can be resolved or ruled out.

From a nurse practitioner’s perspective, Stephanie McDonald, MSN, FNP-BC, AOCNP, echoed this stance on patient education, stating, “It's important for us, after the medical oncology team has their initial consult with the patients, [to] set up a dedicated session with our patients for a 60-minute session for education. It sets the foundation for the journey of their care.”

The experts added that challenges often arise when trying to distinguish between symptoms related to the cancer and those that may signal the development of ILD related to ADC therapy. Conversely, they explained, since many patients have asymptomatic ILD, lung changes that may be associated with this toxicity should also be looked for during routine disease monitoring. For this reason, McDonald’s routine approach includes a baseline assessment of lung function and lymph node prominence prior to initiating treatment.

“There can be a fine line between treating cancer and making it better [vs] creating other symptoms; we want to get ahead of [those],” Elizabeth Castronovo, CNP, stated.

Turning to ILD management, Lisberg and Rugo explained the benefits of immediate high-dose steroid intervention, noting that radiographic changes associated with lower-grade ILD tend to resolve within 3 to 4 weeks of initiating this mitigation approach. Following resolution of this toxicity, many patients are eligible for ADC rechallenge.

“It's a risk-benefit discussion with our patients, but oftentimes our patients are benefiting from these agents,” Lisberg commented. “We have rechallenged in the context of grade 1 [ILD] that's resolved to grade 0, consistent with the labels on these drugs. In many patients, the rechallenge has not led to a recurrence of ILD. This is reassuring that these patients have had their ILD resolved, and [that we can] rechallenge and continue to give patients these therapies. Bad outcomes can potentially occur if you're not catching those grade 1 events, where the patients are asymptomatic; you treat through, and then maybe [the ILD] becomes more severe and irreversible. This toxicity is important and occurs in a limited number of patients, but it can be significant from both a symptomatic perspective and from a radiographic and multidisciplinary perspective in my patients.”

However, Rugo added that data remain sparse regarding the safety of ADC rechallenge after resolution of symptomatic ILD. “We have good [ILD detection and management] systems now, and we've seen situations where there is no mortality from ILD, or the mortality [rate] is extremely low. We are making a lot of progress in this, and there are a lot of similarities between what we do in breast and lung cancer.”

What are best practices for managing oral AEs associated with ADCs?

Turning the discussion to oral toxicities, Castronovo emphasized the importance of prophylactic treatment for AEs such as mucositis and stomatitis, especially for patients who already face challenges with low appetite and weight loss. She explained her patient education process, which includes oral hygiene advice, the benefits of dexamethasone rinses, and details on when and how to call their health care provider if they experience symptoms. These prophylactic measures make treatment pauses less common, she noted. McDonald added that oral pain or inflammation can be managed with topical steroids or antifungals, which may help patients comply with treatment protocols.

Rugo seconded these points and noted that higher-grade oral AEs may be best managed with dose holds and/or reductions. Lisberg agreed, stating, “Even in the context of everything being done perfectly, we have seen significant stomatitis in a limited number of patients. In rare cases when mucositis has been grade 3, we've used an oral steroid burst.”

Notably, the prescribing information for Dato-DXd includes warnings and precautions for stomatitis—including mouth ulcers—and oral mucositis.² Patients are advised to use a steroid mouthwash when starting treatment, as well as hold ice water or ice chips in the mouth during treatment infusion. Dato-DXd may be withheld, reduced, or permanently discontinued based on the severity of these AEs.

How do ADC-related ocular changes affect multidisciplinary collaboration in breast and lung cancer care?

Shifting to ADC-associated ocular toxicities, Neel D. Pasricha, MD, noted that these are relatively unique compared with ocular toxicities seen with other drug classes. He explained that part of the challenge in anticipating and mitigating these AEs stems from the hypothesized off-target nature of these effects.

“This relatively new collaboration and coordination between ophthalmology and oncology is critical,” Sarah B. Sunshine, MD, said. “Identifying [ocular toxicities] earlier is always better, because then we can [manage them] or hold a dose and make a difference in the outcomes.”

She explained the importance of finding trusted eye care specialists and conducting early eye exams, so patients can learn about symptoms to watch for and when to seek further care.

The experts also weighed in on the decision to refer patients to a certain type of eye care practitioner, with Sunshine stating that this depends on the ADC. Patients receiving drugs associated with more severe toxicities should consult with an ophthalmologist, she said, whereas those being treated with agents associated with less severe toxicities can typically meet with an optometrist.

“As ADCs become even more prevalent, oncologists are going to have their personal optometrist, ophthalmologist—whoever they feel comfortable with—that they're going to have easier access for referring to,” Sunshine said. “That's the way the future is going as these ADCs are being used more commonly. Access [to eye care specialists] is going to become less of an issue.”

McDonald added that although baseline eye exams are important, cancer treatment should not be delayed in favor of waiting for an exam, particularly for patients who have had a relatively recent routine exam with no identified issues.

The Dato-DXd prescribing information notes that this agent is associated with ocular AEs, including dry eye, keratitis, conjunctivitis, and blurred vision.² Providers are advised to monitor patients for the development of ocular AEs during treatment. It is also recommended that patients use preservative-free lubricating eye drops and avoid using contact lenses during Dato-DXd treatment. Dato-DXd dosing can be withheld, reduced, or discontinued based on ocular AE severity.

How does gastrointestinal (GI) toxicity management help improve patient outcomes during ADC use?

Switching the conversation to GI toxicities, McDonald noted that Dato-DXd and T-DXd are both highly emetogenic and that prophylactic antiemetic strategies can help maintain proper weight, nutrition, and hydration, as well as bolster patient QOL. However, she highlighted the importance of patient education regarding antinausea agents, sharing that, “Nothing comes without other AEs, so [if] you're adding these medications, you also need to educate these patients that they could get headaches or constipation from these medications. Olanzapine can cause fatigue, especially in [older] or more frail patients.”

Rugo spotlighted the necessity to individualize antinausea regimens based on patient needs and preferences. Particularly for regimens that can cause fatigue, caution and optimized dosing times are keys to decreasing patients’ risk of falls.

The experts also emphasized the importance of administering antidiarrheal medications before and after ADC administration. Castronovo noted the importance of monitoring patient hydration and recommended that patients use stool diaries to map GI triggers that may be exacerbated by certain foods.

“Overall, we can control [GI toxicities]; it's easy to reduce the [ADC] dose, and you can always go back up,” Rugo summarized.

How do ADC-related hematologic changes, neuropathy, edema, and fatigue factor into lung and breast cancer management?

Turning to hematologic toxicities, the experts noted that, in practice, febrile neutropenia is typically managed through proactive or reactive growth factor support, particularly with T-DXd. Lisberg said he urges patients to seek treatment in an emergency department as soon as they develop a significant fever, explaining that emergency staff are well-equipped to manage the sometimes life-threatening nature of neutropenia. Lisberg said he also counsels patients on minor lifestyle adjustments they can make to help avoid exposure to fever-inducing illnesses.

Rugo added, “We need to stay on top of [neutropenia so] we can prevent serious infections and issues for our patients, which can affect their survival and ability to receive [cancer] treatment.”

The T-DXd prescribing information includes warnings and precautions for neutropenia, advising providers to monitor complete blood counts prior to T-DXd initiation and before each dose.¹ Treatment interruptions or dose reductions are listed as neutropenia management strategies.

She also noted that edema and fatigue AEs are particularly difficult to measure, especially because they may arise from cumulative toxicities over time or from causes unrelated to ADCs. Lisberg emphasized that multidisciplinary, individualized strategies are crucial, and health care providers should consider patients’ disease history and QOL outcomes. Consulting the multidisciplinary team to gather data on patients’ baseline characteristics can also help clarify whether an AE is related to treatment vs confounded by preexisting factors.

The panelists agreed that fatigue can also be addressed by increasing the time intervals between ADC doses and by dose reductions. The presence of fatigue should also trigger an investigation into other etiologies, including heart failure, renal insufficiency, and endocrinopathies, particularly in patients who have previously received immunotherapy or have other thyroid disorder risk factors, according to Rugo.

Overall, the experts concluded that comprehensive AE prevention and/or management is critical to preserving both the length and quality of patients’ lives.

“The effectiveness of these therapies and the fact that they're controlling the tumors shifts the discussion in some of our patients in a positive way to QOL,” Lisberg highlighted. “When these patients are coming to see us, they have oftentimes progressed through many other therapies, and the focus at that moment is to make sure we're controlling the tumor. [That] remains the focus throughout the course of therapy, but as a patient shows a clear response and benefit from therapy, we need to be in tune with how they are doing and the AEs they're experiencing. Dose delay can be a great maneuver: a week or two here or there for toxicities, such as eye toxicities or oral mucositis. [We need to] take our cue from our patients. Every patient is different. If [an AE is] bothering them a significant amount, or maybe they have a big family event the next week or something like that, understanding that can allow these patients to continue to obtain a tumor benefit, which is the ultimate goal, but also assure we're providing [them the] best QOL during therapy.”

Hope S. Rugo, MD, FASCO, is director of the Women's Cancers Program; division chief, breast medical oncology; and a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center in Duarte, CA. She is also professor emeritus at UCSF.

Aaron Lisberg, MD, is a thoracic medical oncologist at UCLA and a health sciences clinical instructor in the Department of Medicine at the UCLA Health Jonsson Comprehensive Cancer Center in Los Angeles, California.

Stephanie McDonald, MSN, FNP-BC, AOCNP, is a nurse practitioner at Dana-Farber Cancer Institute in Boston, Massachusetts.

Elizabeth Castronovo, CNP, is a nurse practitioner at Dana-Farber Cancer Institute in Boston, Massachusetts.

Neel D. Pasricha, MD, is an ophthalmologist and surgeon-scientist at the University of California, San Francisco.

Sarah B. Sunshine, MD, is an assistant professor of ophthalmology and a member of the Program in Oncology at the University of Maryland School of Medicine in Baltimore.

References

1. Enhertu. Prescribing information. Daiichi Sankyo; 2025. Accessed April 14, 2026. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true
2. Datroway. Prescribing information. Daiichi Sankyo; 2025. Accessed April 14, 2026. https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Datroway&inline=true