What Advanced Practitioners Need to Know About HER2 (ERBB2)-Mutant Non–Small Cell Lung Cancer: A Case-Based Approach

Case 3: Patient with complications from HER2-mutant–directed therapy

Last Updated: Thursday, November 17, 2022

Stephanie McDonald, FNP-BC, AOCNP, Narjust Florez, MD, and Sarah Tangerini, FNP-BC, look at how to treat a patient who is experiencing complications from their HER2 (ERBB2)-mutant–directed therapy. They discuss the importance of educating the patient on the signs and symptoms associated with treatment-related toxicities as well as the need for a team-based approach in managing toxicities.



Stephanie McDonald, FNP-BC, AOCNP

Dana-Farber Cancer Institute


Narjust Florez, MD

Dana-Farber Cancer Institute

Sarah Tangerini, FNP-BC

Dana-Farber Cancer Institute


Stephanie McDonald: Welcome everybody to this virtual roundtable about HER2-mutant non-small cell lung cancer for advanced practitioners. This is a case-based approach. I'm Stephanie McDonald. I'm an oncology nurse practitioner in the thoracic oncology program at Dana-Farber Cancer Institute in Boston, Massachusetts. I have over 15 years’ experience in caring for patients with cancer.

And joining me today are my excellent colleagues here for discussion, Dr. Narjust Florez and advanced practitioner Sarah Tangerini. I'd just like to take a minute to have them both introduce themselves.

Dr. Narjust Florez: Hi everyone, my name is Dr. Narjust Florez. I'm a thoracic medical oncologist with a particular focus on women with lung cancer. I'm delighted to be here.

Stephanie McDonald: Thank you.

Sarah Tangerini: Hi, everyone. I'm Sarah Tangerini. I'm also a nurse practitioner here at Dana-Farber in Boston. I work with both Dr. Florez and Stephanie McDonald. I have been working in the thoracic oncology program for the past three years, and prior to this, I was focusing in clinical research, and I am very happy to be here today.

Stephanie McDonald: Thank you both for joining me. I'm happy to have you both. Let's talk about case number three. This is a 72 year old non-Hispanic female. She has a 15 year smoking history, pack year smoking history rather, and presented with worsening neck pain. A C-spine MRI was obtained and showed a metastatic lesion in the C4. And a PET CT revealed a right upper lung mass which was two and a half centimeters. There were lytic bony lesions and axillary lymph adenopathy.

Subsequently, the patient had an axillary lymph node biopsy that showed poorly differentiated adenocarcinoma of the lung, TTF1 positive. There was not enough tissue for next generation sequencing when the patient presented, so Guardant360, or liquid biopsy testing, was performed and showed an ERBB2 mutation. She was started on triple therapy with carboplatin, pemetrexed, and pembrolizumab, which as we know is standard of care.

She tolerated the therapy well, but required G-CSF support with Neulasta. While on pembrolizumab maintenance, re-staging PET CT showed disease progression in the CNS, and there was a new lesion in S1 and some breast changes. A brain MRI revealed three metastatic lesions. The patient was asymptomatic, so she was treated with CyberKnife by a local radiation oncologist without any significant complications.

Genomic testing via liquid biopsy revealed that ERBB2 exon 20, and the patient was started and treated with HER2 directed therapy, trastuzumab deruxtecan, for four cycles. She presented to the clinic for evaluation prior to receiving cycle five and was found to be notably increased [...] had shortness of breath, increased in shortness of breath, dyspnea on exertion, and her O2 sat on vital signs 89% on Romer. And previously, she had been averaging 95% to 97% on room air.

Our discussion questions, our first question would go to Sarah and I'll chime in as well. But Sarah, if you could start: what are the differentials that you'd consider here when a patient presents like this?

Sarah Tangerini: Sure. The patient is presenting with new shortness of breath, Dyspnea on exertion, and her oxygen saturation is now 89% on room air and it was previously 95%. As we've discussed in the previous cases, it is also important for us to of get the baseline of what our patients are able to tolerate for exertion prior to starting treatment. Having this information at baseline, how many stairs is she able to walk up? Or what's the distance that she was able to tolerate prior to starting treatment?

If we see that there is a significant change from her baseline, then it's important for us to work this up and figure out what's causing it. The differentials that I would consider [...] So the standard differentials when someone presents with dyspnea: a pulmonary embolism, so a blood clot in the lung. Does the patient have pneumonitis? Is there some new inflammation in the lungs from the treatment?

Is this a pneumonia? Is she presenting with a fever or other infectious symptoms? Is this an infection versus it being a pneumonitis? Does she have a plural effusion? A lot of the time, our patients do present with plural effusions, so getting a scan to see if there is new fluid in the lung is also important. But then, with this treatment, it really is important to note, does the patient have new LVEF dysfunction? Specifically with trastuzumab deruxtecan, we are concerned that they may have new cardiac dysfunction. That could be a potential differential.

Or is this a new pericardial effusion? Or is this just disease progression? Is she not responding to treatment? Those would be the differentials that I would go through and think of if a patient were to present with these symptoms.

Stephanie McDonald: I agree. That's very comprehensive. Those are the things that I would in general think of in this scenario. If you were the actual advanced practitioner taking care of this patient, how would you start working this up?

Sarah Tangerini: Sure. If I'm thinking, is this a pulmonary embolism? I would want to know, is this patient on a blood thinner? If they're on a blood thinner at baseline, probably not a PE. I would want to see if it's possible to obtain a chest x-ray or a chest CT scan. In our facility, it is easy to get a same day CT scan, so I might want to lean towards getting that. Or is it more appropriate to just get a chest x-ray and see if there is new fluid in the lungs? Is there a new consolidative opacity that might lead us to think it's a pneumonia?

Prior to getting a CT chest, what's appropriate? It depends on the patient, and how they're presenting, and how severe their symptoms are. If I can only get a chest x-ray then I may want to just get that first and then decide on what I want to do going forward. If there are any abnormalities seen on the chest x-ray, then I might want to get a chest CT scan.

I might want to do an O2 walk test in clinic, because if the patient is satting at less than 90% on room air, is it safe to even send the patient home with these symptoms? Or is this something where she needs to be worked up in the hospital or sent home with oxygen? Getting an O2 walk test is also important while the patient is in clinic.

What are her vital signs? Does the patient have a fever? Is she hypotensive? Does she look dehydrated and are there signs of infection? That would also be important to consider. And then also, looking at just their lab tests, the CBC and a CMP, if we see elevated white blood cell count, then we might lean towards it being an infection and maybe starting with treating with an antibiotic if the scans do show signs of a pneumonia.

And then also, considering an echocardiogram. These sometimes are harder to get scheduled and we may not be able to do the same day. So really determining, is it, again, safe to send the patient home? Do we think this is cardiac related? Do we think the patient needs to be sent to the hospital to be worked up more urgently? Or is this something that can wait until she can get an echocardiogram within the next few weeks? Those would be the things that I would do to work this patient up.

Stephanie McDonald: Yeah. Again, very comprehensive. I agree with how you would approach the patient. I would probably do the same thing depending on what their functional status was, what their vital signs were. Are they hemodynamically stable? Are they able to have this workup in the outpatient setting? Or do they need to come in house and be admitted or go to the local emergency room.

Depending on what your practice setting is, do you have access to imaging in a reasonable amount of time? Do they need to be admitted or go to the ER for more of an expedited workup? All things to consider. Dr. Florez, if it showed that it was a drug related pneumonitis, how would you treat this?

Dr. Narjust Florez: Well one of the keys about treating ILD induced by HER2 directed therapy is steroid based therapy. The hope is that steroids decrease the inflammation. Because it's a problem when it happens, and it's also a problem with this scarring tissue after the inflammation happens, so the steroids have two goals. And as we say, steroids are so beneficial with patients with lung cancer. I barely have any patients that don't like to go on steroids.

That's very important. We need to remember PJP, also known back in the day as PCP prophylaxis in patients. These patients will require a course of prednisone. This is very different than the pneumonitis for an immunotherapy. The ILD for HER2 directed therapy requires long tapers. We're talking about weeks, months. And you won't see that magical recovery that we see with immunotherapy, when you give them prep and the next day they're like, "Oh I feel great." No, this is different. Very different. It takes a longer time.

Patients that have grade two, which means they're hypoxic, grade three or four, should be seen initially […] because there's a high risk for the compensation at home. What happens with cancer treatment? What are we going to do? Of course, if it's a grade two or higher, we are not going to go back to that drug because the risk of permanent damage. We don't go back.

Keep the pulmonologist in your speed dial. And sometimes, we re-challenge patients with already a low dose of prednisone. They have a low dose of prednisone, and we restart the drug with very close follow up. Another option is, rumor has it that is a TKI, tyrosine kinase inhibitor, that may get approved soon. That could be an option for us in two or three months. You heard that here first, so we're giving you all that information. In the future there may be a TKI that could be a replacement.

Otherwise, we need to call on all friends: gemcitabine or docetaxel that are still parts of treatment for next line of therapy. But if patients are too sick, it's too risky to re-challenge. The risk outweighs the benefit here.

Stephanie McDonald: Absolutely. Well said. Thank you. Key clinical takeaways to this case study. It's really important to know the adverse effects and the side effects related to trastuzumab deruxtecan, and to be able to get your differentials and rule out other causes of suspected pulmonary toxicity. You really want to ensure you're not missing possible infection, a pulmonary embolism, LVEF dysfunction, pericardial or pleural effusion, or another cause. Always have your ears up when somebody comes in feeling that way.

Interstitial lung disease and pneumonitis, there have been reported fatal cases on trastuzumab deruxtecan, so you have to take these symptoms very seriously. You really need to monitor for, and promptly investigate, any respiratory complaints like Sarah and Dr. Florez have gone over. So any cough, dyspnea, fevers, new or worsening respiratory complaints, and likely permanently discontinue trastuzumab deruxtecan in all patients with grade two or higher ILD or pneumonitis.

And the key is educating these patients on the signs and symptoms associated with toxicities related to trastuzumab. I can't stress that enough. The importance of chemotherapy teaching with these patients to know what to expect with these drugs, the side effects, when to call. And then again calling on our friends, a team based approach in managing side effects and toxicities. We are not alone. We need to work together. We need to rely on our advanced practitioner colleagues, our physician colleagues, other specialties, pulmonologists, cardiologists, anybody involved in the case that could help manage and tailor the care to their specific side effects. So a team based approach.

This brings us to the end of this discussion. Please see other segments for further discussion about HER2 mutant non-small cell lung cancer or visit advancedpractitioner.com. Thank you.