Structure to Safety: A Nurse's Guide to Safe ADC Care

Undesrtanding ADC structure can lead to informed toxicity management.

Despite ongoing advances in diagnosis and treatment, the number of lives lost to cancer remains unacceptably high. In 2022, nearly 10 million cancer-related deaths were reported, along with twice as many new cancer cases.¹ Although conventional chemotherapy continues to be the most widely used treatment option, its efficacy is limited by indiscriminate cytotoxicity and a narrow range of therapeutic safety.²

However, the use of antibody-drug conjugates (ADCs) is on the rise in oncology—and for good reason. Their potential to reduce the impact of treatment on healthy cells and improve patient outcomes is promising. Given the growing interest in ADCs, how can nurses better understand this class of drugs to optimize care and proactively manage toxicities?

ADCs: Has the “Magic Bullet” Arrived?

ADCs have come a long way since German scientist, physician, and Nobel laureate Paul Ehrlich first envisioned a targeted drug, or “magic bullet,” in the early 1900s.³ Now, more than a century later, Ehrlich’s concept has ushered in an exciting new era of treatment options. As of 2025, over 15 ADCs have been approved for use in oncology globally, with hundreds more in development or undergoing clinical investigation.⁴

Unlike standard chemotherapy, ADCs are designed to deliver and release cytotoxic agents in a more targeted manner by incorporating 3 key components: a monoclonal antibody, a payload, and a chemical linker. Each component has a unique role in this complex delivery system. Simply put: the antibody delivers the payload to the target cell, the linker releases the payload, and the payload does its cytotoxic duty. Each component of an ADC is specific to its function and aligned accordingly.

“For example, if you have HER2-positive breast cancer, we have a monoclonal antibody that targets only HER2,” Erica Doubleday, MS, FNP-C, BSN, RN, said in an interview with Oncology Nursing News. Doubleday, who is the advanced practice provider director of cancer services at Ochsner Health in New Orleans, Louisiana, shared the impact this can have on patients. “There tend to be fewer [adverse effects (AEs)] with these drugs as the ADC is targeted at cancer cells, causing much less damage to other cells around the body.”

Although the antibody’s function is to guide payload delivery, oncology nurses should understand how a particular antibody may affect the patient, how it works, and where it is binding, explained Sarah Donahue, MPH, AOCNP, a breast oncology nurse practitioner at the University of California San Francisco Breast Care Center.

“Antibodies are very specific,” Donahue said. “They can have positive or negative effects. Knowing how the antibody affects cells and [what the associated AEs are] is also important.”

Payload Diversification and Linkers

Oncology nurses should be familiar with the types of payloads in the ADCs they administer and their associated toxicities. Common payloads include microtubule inhibitors such as maytansinoids and auristatins, DNA-alkylating agents such as calicheamicin and pyrrolobenzodiazepine PBD, and TOP1 inhibitors.⁵

AEs vary based on the ADC administered and may include gastrointestinal effects such as nausea/diarrhea, neutropenia, hair loss, and vision/eye issues. AEs may vary in severity according to the payload, the payload’s effect on nontargeted tissue, and each component of the ADC—both separately and combined—although most toxicities can be attributed to the payload.⁶

Payload diversification refers to the use of various cytotoxic agents to improve efficacy, overcome resistance, enlarge the therapeutic safety window, and broaden therapies to target more cancer types.⁵ Doubleday explained that diversification allows providers to “tailor treatment to the tumor’s biology, affecting the biology of that specific tumor and not all cell lines.” She also added that, “with chemotherapy, some of the tumors were able to outsmart us, and with ADCs, we are now back to trying to outsmart the tumors.”

Understanding the payload’s mechanism of action alone is not enough; nurses should also be aware of the target. When deruxtecan is attached to trastuzumab, for example, it will be delivered to different parts of the body than when it’s attached to datopotamab. According to Donahue, this matters because “although the payload is targeted to destroy malignant cells, it may, and often does, bind to other cells. So, knowing both the target and the effects of the payload helps nurses anticipate and manage toxicities.”

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) and sacituzumab govitecan (dato-DXd; Trodelvy) are examples of diversified payloads that disrupt DNA replication. Other diversified payloads being explored include transcription inhibitors such as RNA polymerase II inhibitors; proteolysis-targeting chimeras, which induce protein degradation; radionuclides; and immune-stimulating agents.⁵

Linkers are the biochemical binding component of ADCs that connect the antibody to the payload. Their purpose is 2-fold: to maintain stability of the ADC as it moves through the bloodstream and to release its payload when it reaches the target. Doubleday explained that “cleavable linkers release the drug inside the tumor, [whereas] noncleavable linkers limit drug release to targeted cells exhibiting the cancer.”

Whether a linker is categorized as cleavable or noncleavable is based on intracellular factors that help control when and where the payload is released. If the stability of the ADC is not maintained, the payload may be released prematurely, causing significant toxicity. The intended clinical effect will be suboptimal if the payload is released too soon. Although understanding glutathione reduction, nonreducible bonds, and amino acid residues is not paramount, it is helpful for nurses to know how linker performance may affect the patient.

ADC Composition and Safety Profile

ADCs share similarities and differences in terms of composition and safety profiles. The associated toxicities of each ADC’s antibody, payload, and linker may differ, as shown in the table below.^5,6

ADC, antibody-drug conjugate; dato-DXd, sacituzumab govitecan; ILD, interstitial lung disease; T-DXd, trastuzumab deruxtecan.

Knowing all there is to know about ADCs is not a prerequisite for administering treatment, but nurses must be knowledgeable about the drugs they give and how they affect the patient. “From a nursing point of view, what matters to us is to understand the effects and [AEs] of the medication,” Donahue said.

Nurses should have solid—even if basic—knowledge about antibodies, linkers, payloads (including type and target), how they work, potential AEs (on-target and off-target), administration and safety precautions, drug-drug interactions, and patient monitoring for and management of toxicities.

Elizabeth Prechtel Dunphy, DNP, RN, ANP-BC, AOCN, a gastrointestinal oncology nurse practitioner at Abramson Cancer Center Penn Presbyterian and advanced senior lecturer at the University of Pennsylvania School of Nursing, both in Philadelphia, acknowledged that nurses should become familiar with individual drugs based on their specialty, although this may be easier for an advanced practice provider.

“For infusion nurses, it may be more challenging because they work with so many drugs,” Dunphy said. She encouraged nurses to learn about new and unfamiliar medications by attending presentations offered by pharmacists or pharmaceutical educators or seeking out information from the many resources available, including package inserts, continuing education, drug company websites, and professional literature.

Toxicity Management and Patient Education

Effectively managing toxicities associated with ADCs is a continuous process, beginning with the first patient encounter after diagnosis. This is when the knowledge gained about the ADC that the patient is prescribed has a crucial impact.

“I like to have a conversation with them about what the drug is, why we are using it, and toxicities to watch for. I describe to patients that there are antigens and linkers, and the medication recognizes and is driven toward the target like a warhead to the cancer cells and releases the medication upon arrival,” Dunphy said. “This helps limit some of the toxicity as it’s location-specific.”

Dunphy also recommended reviewing the information with patients, including asking them to restate the information themselves. Patient education should include what symptoms to look for, when to call in with issues, and when to return to the clinic, Dunphy explained.

Donahue advises nurses to “keep it simple.”

“List out the top 5 [AEs] and what to look for. Give them paperwork on less common effects. Educate on what to do if symptoms start. If they are still nauseous, for example, after taking the second pill, call us. If they vomit, no matter where they are in the process, call us. A lot of discussion on when to call,” she continued. For issues such as diarrhea, patients should be advised to have antidiarrheal medication available so they are prepared if symptoms have sudden onset.

Being informed about when to call can also spare patients an unnecessary trip to the emergency department. Most infusion centers are closed at night, so if a patient develops a fever early in the evening and calls the on-call provider, they will be instructed to get evaluated in the emergency department. If the fever starts an hour before the center opens, waiting to call during office hours may be advisable. “Patients have their own experience with their health, with different medications, and how they’ve managed symptoms such as nausea in the past. Educate patients that AEs are not based on past experience. If the treatment is new to them, the symptom is new as well,” Donahue said.

Common AEs of ADCs may differ with the type of cancer. Doubleday explained that many ADCs given for breast cancer damage the DNA. “We see a lot of ILD [interstitial lung disease], so for us, shortness of breath is very scary.”

Doubleday urges patients to call early if they experience any breathing issues, as ILD can be lethal if not treated promptly. If addressed early, treatment can be paused and restarted; if not caught until later, treatment may have to be changed, even if the patient was responding well. Patients reporting shortness of breath should have a chest x-ray and be treated with steroids as indicated.

Avoiding ambiguous terminology when educating patients reduces confusion. “Some of the education may instruct them to call with a persistent cough,” Doubleday said. “Everyone’s definition of ‘persistent’ could be different. Some may think a cough after 6 weeks is persistent; some may say 3 days. I usually tell patients if they have a change from how they feel right now, I need to know.”

Doubleday also encourages patients to keep a diary, with day 1 being the day of treatment, and to write down everything that happens, or the absence of events. At their next appointment, the patient can share information with the nurse without having to rely solely on their memory.

Importantly, nurses should listen to their patients. “Sometimes [information that patients tell nurses] gets brushed off, and it’s a big thing,” Doubleday said. “I had a patient with a temperature of 99 °F who said it was a fever for them. Their normal temperature was 97 °F. We did a workup, and the patient had an infection. [If] we waited until they reached our standard threshold, they could have been septic.”

Doubleday recognizes that not every patient is a reliable historian, but nurses can interpret patient feedback. “A lot of them know their bodies better than we do. Patients often feel very unheard, yet they usually know what they are talking about. Listen to them.”

References

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2. Anand U, Dey A, Singh Chandel AK, et al. Cancer chemotherapy and beyond: current status, drug candidates, associated risks and progress in targeted therapeutics. Genes Dis. 2024;11(4):101211. doi:10.1016/j.gendis.2024.101211
3. Das S. The next wave after immunotherapy in cancer drug development—back to the future. JAMA Oncol. 2025;11(7):686-687. doi:10.1001/jamaoncol.2025.0720
4. Hong Y, Nam SM, Moon A. Antibody-drug conjugates and bispecific antibodies targeting cancers: applications of click chemistry. Arch Pharm Res. 2023;46(3):131-148. doi:10.1007/s12272-023-01433-6
5. Conilh L, Sadilkova L, Viricel W, Dumontet C. Payload diversification: a key step in the development of antibody-drug conjugates. J Hematol Oncol. 2023;16(1):3. doi:10.1186/s13045-022-01397-y
6. Ballestín P, López de Sá A, Díaz-Tejeiro C, et al. Understanding the toxicity profile of approved ADCs. Pharmaceutics. 2025;17(2):258. doi:10.3390/pharmaceutics17020258
7. Sands J, Ahn MJ, Lisberg A, et al. Datopotamab deruxtecan in advanced or metastatic non-small cell lung cancer with actionable genomic alterations: results from the phase II TROPION-Lung05 study. J Clin Oncol. 2025;43(10):1254-1265. doi:10.1200/JCO-24-01349
8. Tahara M, Okano S, Enokida T, et al. A phase I, single-center, open-label study of RM-1929 photoimmunotherapy in Japanese patients with recurrent head and neck squamous cell carcinoma. Int J Clin Oncol. 2021;26(10):1812-1821. doi:10.1007/s10147-021-01960-6