The Use of Antibody–Drug Conjugates as Novel Therapies for Patients With Advanced NSCLC: Advanced Practice Professional Considerations

Key Takeaways

• It is paramount to educate patients with advanced NSCLC at the time of disease recurrence about the importance of retesting biomarkers that may help guide further treatment decisions.
• Patient eligibility for the approved HER2-targeted ADC, trastuzumab deruxtecan, is based on HER2 mutation status or HER2 overexpression level in the tumor.
• ADCs that target HER2 or TROP-2 are associated with adverse events that are not common with other therapies used for lung cancer; thus, educating advanced practice professionals and patients about these adverse events is key.

Antibody–drug conjugates (ADCs) against HER2 and TROP-2 are quickly emerging as therapeutic options for the care of patients with advanced non-small-cell lung cancer (NSCLC). In this commentary, we lay the groundwork for key topics to be covered during our upcoming live webinar, such as identifying patients with lung cancer who are eligible for ADCs at recurrence, exploring current clinical evidence related to the use of approved and investigational ADCs, and the management of ADC-related adverse events (AEs) in your patients with advanced NSCLC.

Assessing for Patient Eligibility for HER2 and TROP-2 ADCs

Blanca Ledezma, MSN, NP: Defining a patient with recurrent advanced NSCLC as eligible for an ADC may be guided by biomarkers expressed by the tumor. The results of the original biomarker assay performed at diagnosis are always referenced, and they help determine whether a patient has actionable biomarkers for a targeted therapy (ie, HER2) or immunotherapy (ie, PD-L1). For instance, in the case of the HER2-targeted ADC, trastuzumab deruxtecan, a patient may be eligible for this therapy if their original biomarker assay performed at diagnosis detected the presence of a HER2 mutation. When patients meet with a healthcare professional (HCP), the treatment options for recurrence (eg, clinical trial, standard of care chemotherapy, or an ADC) are explained, and patients then have a choice to make, but only after all the information is provided. That being said, I believe it is important for HCPs to understand the basics of ADCs (ie, their mechanisms of action), current data supporting their use for recurrent NSCLC, and the associated AEs so they can better inform and educate patients.

To explain to patients how ADCs work, I like to use a Trojan horse analogy to simplify the explanation. I tell patients that the novel treatment they are about to receive uses an antibody that acts like a Trojan horse carrying within it a chemotherapy agent. When the ADC reaches the target cell, it then releases the chemotherapeutic agent in a novel way.

It is also very important that HCPs take the time to establish a good baseline for where the patient is regarding their health status and treatment journey before initiating any new treatment. Do they have any underlying comorbid conditions? If so, where are they at baseline? How do they deviate from baseline after they start treatment? Then we evaluate them at every point of contact, whether it be in the infusion room or follow-up in the clinic, and determine whether they are experiencing any toxicity. I convey the importance of communicating with their HCP if there is any type of deviation from baseline, making them an active member in their own care.

Next Steps for Patients With NSCLC and Disease Recurrence

Denise Rouse, MS, PA-C: Patients come to us at different phases of their journey. In most cases, advanced practice professionals (APPs) will see these patients throughout their treatments, which can be every 2 to 3 weeks or monthly. By the time of disease recurrence, we hopefully have established a good rapport, we know their families, and they trust us. Disease recurrence can be a very scary time for patients, and at this point, we must re-educate. I find each time there is a change of treatment that it is a good idea to sit down with patients and discuss the new plan. What is this new modality? What does this mean for you? How might this affect your day-to-day life? What kind of toxicity might you experience? What kind of follow-up is needed?

At recurrence, I also believe APPs should discuss the importance of looking for new markers, which may require another liquid biopsy. If possible, we should take another biopsy of the tumor as it progresses because patients can lose that initial actionable mutation and/or develop another that could cause treatment resistance. In such cases, the care team needs to know the next steps. However, some emerging or investigational ADCs such as those targeting TROP-2 may not be limited by the level of TROP-2 expression in the tumor, and that is something to keep in mind and that requires additional patient education.

Current and Emerging Clinical Data on ADCs in Advanced NSCLC

Denise Rouse, MS, PA-C: In my opinion, ADCs are an exciting new treatment modality for our patients with advanced NSCLC. They are changing the way we think about and treat various solid cancers. To date, there is 1 FDA-approved ADC for HER2-mutant lung cancer and those with HER2 IHC3+ status: trastuzumab deruxtecan, which is used in the approximately 4% of patients with this less common mutation. Moreover, there are many studies on HER2 and TROP-2 ADCs out there, including the single-arm international phase II DESTINY-Lung01 trial (NCT03505710) and DESTINY-Lung02, in which trastuzumab deruxtecan showed strong antitumor activity, and the ongoing multicenter, open-label, dose-expansion phase I TROPION-PanTumor01 trial (NCT03401385), in which datopotamab deruxtecan, a TROP-2–directed ADC, has demonstrated highly encouraging preliminary antitumor activity in patients with relapsed advanced NSCLC regardless of TROP-2 expression level. We continue to learn more about these drugs for both people with and people without a known driver mutation and disease progression.

As more ADCs become available in the clinic, APPs will need to understand their toxicities, how they differ from one another, and how they are managed differently than some of the other anticancer therapies (eg, chemotherapy or immunotherapy) used for our patients with advanced NSCLC. At least in the lung cancer field, we may not be as familiar with some of the ADC-related toxicities. For instance, we do not see a lot of mucositis; we do see pneumonitis, but it is handled a bit differently when it is related to an ADC. APPs can expect to see some ocular toxicities with ADCs, which are also uncommon with other therapies used for lung cancer. In our upcoming webinar, we will cover topics including how to identify, monitor, and manage these novel toxicities with ADCs and how to best educate patients about them.

Patient Resources in Lung Cancer

Blanca Ledezma, MSN, NP: Advocacy groups are a phenomenal resource for our patients. LUNGevity, among others, is a great one for patients. Many advocacy groups like this provide booklets that are accessible for free on the internet and are written in patient-friendly language that patients can understand. I also encourage our patients to order these booklets, which are sent to their home, and bring these resources to their appointments so we can review them together.

In addition, some specialized testing is typically done through third-party laboratories. These laboratories are phenomenal at ensuring that the cost of the test or retest is covered, and they may have a robust financial assistance program when needed. It is reassuring that we can tell patients that cost is not something they have to worry about when considering retesting their tumor regardless of whether they have commercial insurance, a preferred provider organization, a health maintenance organization, Medicare, or Medicaid.

Denise Rouse, MS, PA-C: The Lung Cancer Research Foundation is another great resource if patients are interested in biomarkers and molecular testing. The National Comprehensive Cancer Network has free patient-centered booklets that can help patients understand more about biomarker testing and available treatments for NSCLC. These resources can help answer questions like “What are the different types of therapy?”; “What is molecular testing?”; and “Why is it important?”

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Your Thoughts?

What, if any, is your experience with regard to the use of ADCs for recurrent/advanced NSCLC? Join the discussion by leaving a comment and answering the polling question. Click this link to register for our upcoming live program along with Edward B. Garon, MD, MS, covering the mechanism of action of ADCs, the latest clinical data on the use of these novel agents in advanced NSCLC, and practical clinical insights on how to monitor for and manage ADC-related AEs.