Thoracic Oncology Advances and Toxicity Management

Rapid therapeutic developments in thoracic oncology, including next-generation EGFR inhibitors, ALK inhibitors, and antibody-drug conjugates (ADCs), have significantly altered the lung cancer treatment landscape. While these therapies offer unprecedented survival benefits, they introduce unique, complex toxicity profiles that require vigilant management.

In this clinical interview, Beth Sandy, MSN, CRNP, FAPO, an advanced practice provider at Penn Medicine's Abramson Cancer Center, discusses practical strategies for oncology nurses. Sandy highlights key toxicities such as dermatologic rash, severe diarrhea, interstitial lung disease, and mucositis, emphasizing the critical importance of early proactive intervention. She also addresses financial toxicity barriers and highlights the evolving role of APPs in a collaborative, multidisciplinary care model. By partnering with pharmacists and subspecialties like dermatology and ophthalmology, oncology nursing teams can successfully navigate complex regimens to preserve patient safety and treatment adherence.

What is the single biggest advance in small cell lung cancer targeted therapy over the last year that oncology nurses need to have on their radar?

Naming a single one is really hard because there have been so many advances. I think one of the biggest things that's really exciting in the ALK space is the 7-year update of the CROWN (NCT03052608) study, where we're seeing that over half of patients are still progression-free on lorlatinib (Lorbrena) at 5 years. So they haven't even reached the median progression-free survival yet, but over half of them at 5 years haven't even progressed, which means likely our survivals are going to be measured in the 5- to 10-year mark at this point for metastatic disease. That's pretty incredible.

I think in the EGFR space, we've seen a lot more treatment options become available, and particularly frontline treatment. We're also seeing really long progression-free and overall survivals.

And then lastly, in the HER2 space, we now have for the first time a HER2-targeted therapy available in the frontline setting. So, no longer do they have to get chemotherapy upfront; we can give them that oral zongertinib (Hernexos) in the frontline setting, and we've seen really nice responses there.

How do you approach counseling for patients experiencing dermatologic or gastrointestinal toxicities from EGFR inhibitors to prevent premature treatment discontinuation?

I think we've moved towards being more aggressive at managing and even preventing the dermatologic toxicities with EGFR inhibitors. Particularly, our two main frontline treatments are either osimertinib (Tagrisso) with chemotherapy or amivantamab (Rybrevant)-lazertinib (Lazcluze). They both have pretty similar outcomes but very different treatments. And I think that with amivantamab-lazertinib, using preventative skin care regimens has really changed the patient's ability to tolerate that. With the osimertinib-chemotherapy regimen, which is frequently used in the frontline setting, I think I'm a lot quicker to move to oral doxycycline if they start having a rash that's becoming irritating to them, as opposed to waiting longer.

Now, for the gastrointestinal toxicities with EGFR inhibitors, it depends on the drug you're using. We don't see it too much with amivantamab-lazertinib; typically it's low-grade, and over-the-counter antidiarrheals are very effective. Now, if you're using a drug like afatinib (Gilotrif), which we still do use, especially for patients who have some of the more uncommon EGFR mutations, those patients need to start the antidiarrheal upfront—or the moment they're starting to have diarrhea—because we know that the grade 3 or 4 diarrhea rate is a lot higher with that drug.

With the rapid integration of antibody-drug conjugates (ADCs) into thoracic oncology, what is the most crucial adverse event monitoring priority for advanced practice providers (APPs)?

It really depends on which ADC you're using. We now have at least three antibody-drug conjugates that we can use, and they all have very different toxicity profiles. If you're using trastuzumab deruxtecan (Enhertu), which is in the HER2 space, I think interstitial lung disease (ILD) is one of the main things that we worry about. Now, there is a chemotherapy payload, so we do worry about some of the GI effects and myelosuppression, but the ILD rate is real with that, and we want to catch that as early as possible.

With the other drugs, it all depends. For example, datopotamab deruxtecan (Datroway) is also in the EGFR space; however, mucositis is the main thing there, and really preventing mucositis is key to having tolerability on that drug. The third one, tisotumab vedotin (Tivdak), has yet a totally different toxicity profile. Typically, we're looking to manage peripheral neuropathy there.

What key practical strategies do you use to help patients navigate financial toxicity and access patient assistance programs for these oral targeted agents?

Financial toxicity is a real thing, particularly with the oral agents. So, I look for so much help from our clinical pharmacists and from our triage nurses in my practice. Our pharmacists are really helpful at getting prior authorizations and looking for co-pay assistance programs. But, we all know with Medicare, we cannot use those things. So it is really looking at: What is their out-of-pocket going to be? Is this something that they are going to qualify for patient assistance, and then going to that specific company? And that's where our triage nurses are really helpful; they have the forms for each of those companies to apply for free drug if the patient qualifies.