Navigating Toxicities and Monitoring Strategies for Tyrosine Kinase Inhibitor Therapies for Lung and Breast Cancer

Beth Sandy, MSN, CRNP, FAPO, Abramson Cancer Center, Philadelphia, Pennsylvania, delivered a comprehensive overview of tyrosine kinase inhibitor (TKI) therapy, focusing on clinical use, toxicity management, and monitoring strategies across multiple tumor types at the 2025 Oncology Learning Network APP Institute.

She highlighted key agents such as osimertinib, lorlatinib, and amivantamab-lazertinib for lung cancer treatment, along with strategies for managing rash, hyperlipidemia, and hypertension, and emphasized the importance of oral adherence in targeted therapy.

Transcript:

Hi, my name is Beth Sandy. I am a nurse practitioner in thoracic specialty of oncology at the University of Pennsylvania in Philadelphia and the Abramson Cancer Center. I gave a talk for the Oncology Learning Network, OLN, APP Institute. It was a virtual conference that we presented mainly targeting solid tumors and the treatments that are available, and their toxicities.

In particular, my talk was on tyrosine kinase inhibitor therapy, which is a very broad category. We talked about navigating clinical use and the toxicities and monitoring strategies. I'll give a high-level overview of what I discussed.

One of the first things I talked about was what is a tyrosine kinase inhibitor? Tyrosine kinase inhibitor is a small molecule, oral therapy. These are pills that we use in multiple different types of cancer. I primarily work in lung cancer, and we have a lot of tyrosine kinase inhibitors because we've identified a lot of targeted therapies that we can use as therapeutic targets in non-small cell lung cancer. These drugs actually will target a receptor or mutation, but they actually work at the intracellular level. Unlike larger molecules like monoclonal antibodies that will bind and sort of work at the extracellular, tyrosine kinase work at that tyrosine kinase domain.

When we talk about the different tyrosine kinase inhibitors, the majority that I talked about were in lung cancer. One of the most common ones is EGFR inhibitors. We primarily talked about osimertinib and the combination of amivantamab-lazertinib, now amivantamab is a bispecific antibody. That's a monoclonal antibody, but the lazertinib is a TKI. Those 2 regimens are the most common ones which are used frontline for EGFR. 

We did talk about the rash associated with that, and things that we can do for that, for example, the amivantamab-lazertinib, we definitely do prophylactic doxycycline to prevent rash since the rash is higher. By doing that, you really cut in half the rate of rash and certainly that of grade 3/4 rash. That was really beneficial there. With osimertinib, if you're using that pill either by itself or with chemotherapy, the rash doesn't tend to be as severe. I don't typically prophylaxis with doxycycline. I use it reactively for those patients.

We talked a little bit about ALK and ROS1 inhibitors in non-small cell lung cancer. A lot of very unique toxicities with the different drugs that are approved here. We did talk about lorlatinib in particular. One of the more common ones we're using frontline for ALK-positive non-small cell lung cancer and just how we manage things like the hyperlipidemia. We have to be pretty aggressive with that as 95% of patients experience it. 

We talked about KRAS inhibitors. Interestingly, they're not tyrosine kinase inhibitors. They selectively bind at the cysteine in the G12 pockets, so technically not a TKI, but an oral-targeted therapy. Mainly diarrhea is the side effect of these, but it’s usually easily controlled with over-the-counter antidiarrheals, pretty uncommon, less than 5% of the time that we really need a drug. 

We talked about a lot of other TKIs in non-small cell lung cancer, BRAF inhibitor therapy, RET inhibitors, MET inhibitors, HER2 mutation inhibitors, which are TKIs now that are oral for non-small cell lung cancer. Then we moved on and we talked about breast cancer TKIs. The PIK3 kinase inhibitors, the CDK4/6 inhibitors, those were the main ones that we discussed. 

We talked about things like the treatment of hyperglycemia in the PIK3 kinase inhibitors—things like using metformin in these patients and then increasing the metformin dose, titrating up, specifically with inavolisib and the capivasertib. Generally, patients are able to stay on therapy but typically looking at that. We talked about the rash a little bit as well. Usually, topical corticosteroid creams will work there. We also talked a little bit about CDK4/6 inhibitors in breast cancer as well, managing the neutropenia there and looking out for that.

Then I ended up with talking about the multi-kinase inhibitors that we use in GI and GU, and non-small cell lung cancer, and sort of the hypertension that goes with that, just how we really want to tailor the management of hypertension to maybe what their comorbidities are. There's a paper by Pandey et al in one of the renal journals that did a really nice job at looking at management of hypertension in patients with cancer. I have a slide just talking about being very specific about what their comorbidities are when we're treating patients for hypertension with cancer.

The last thing that I ended up talking about was oral adherence. These are pills, we have to make sure that patients are taking it properly at home. The one key that I gave there was that I like to ask patients when they come in, how are you taking your lorlatinib? As opposed to, you're taking it once a day, right? Or like alectinib is something that generally patients are on 4 pills twice a day. Instead of saying, you're taking 4 pills twice a day? I would say, tell me how you take your alectinib. Then we can make sure that they're taking it properly. 

I think we struggle a little bit with oral adherence and how we make sure that patients are taking this. It's something we have to pay a lot of attention to in the future.

Source:

Sandy B. Tyrosine Kinase Inhibitors Therapy: Navigating Clinical Use, Toxicities, and Monitoring Strategies. Presented at Oncology Learning Network APP Institute; December 18-19, 2025. Virtual.