Nursing Strategies for the 3 First-Line Regimens in EGFR-Mutated NSCLC

The NCCN now lists 3 category 1 preferred first-line regimens for EGFR-mutated advanced non–small cell lung cancer (NSCLC): osimertinib (Tagrisso) monotherapy, osimertinib plus platinum chemotherapy and pemetrexed, and amivantamab-vmjw (Rybrevant) plus lazertinib (Lazcluze).^1-3 Each carries a distinct toxicity, monitoring, and adherence burden that nursing teams work to manage, and patients often arrive with strong preconceptions about which option is right for them.

In a CancerNetwork®-hosted Around the Practice program, a panel of oncology nurses discussed how they build baseline assessments, patient and caregiver education, telephone triage, and toxicity grading around these 3 regimens. They also discussed the particular attention they pay to the toxicities that most often threaten adherence to osimertinib over years of continuous therapy.

The panel was moderated by Elizabeth M. Dennis, MSN, APRN, FNP-C, of Texas Oncology. She was joined by Stephanie McDonald, NP, and Michelle Dupille, RN, an oncology nurse navigator in thoracic oncology, both of Dana-Farber Cancer Institute.

Establishing a Baseline and Preparing Patients Before Cycle 1

Dennis: Nursing care starts before the first dose. Can you walk us through what the baseline assessment looks like, and what we should document before patients start these regimens?

McDonald: When a patient comes in to see us, we need a good baseline established on day 1 so we know what’s new once they start treatment. Especially for these EGFR-type treatments, we need a good skin and nail assessment, and we need to know their pulmonary symptoms: Do they have a baseline cough? Do they have [chronic obstructive pulmonary disease] COPD or oxygen requirements? What’s their cardiac history? Do we have baseline EKGs looking at their QTc interval? We want baseline EKGs on certain treatments to evaluate ejection fraction, especially for patients at high cardiac risk, and a good baseline ocular symptom history. The key is a thorough head-to-toe assessment so we can recognize changes early and keep patients on treatment with excellent quality of life.

Dennis: I’ll piggyback on that—making sure labs are checked prior to cycle 1, day 1. We want to look at renal function before starting pemetrexed, and whether patients are already on blood thinners or have venous thromboembolism [VTE] risk factors, especially for those going on amivantamab plus lazertinib. Medication reconciliation matters too: we need to know if patients are on strong CYP3A4 inhibitors or QT-prolonging agents. We should also make sure patients know that acid-reducing agents aren’t a barrier with osimertinib the way they are with some other oral oncolytics.

Michelle, timing shapes education, and it differs by regimen. In the first 8 weeks, we see VTE risk and skin toxicity with amivantamab plus lazertinib, vs the gastrointestinal effects we see with osimertinib monotherapy, and myelosuppression and nausea when we add platinum chemotherapy to osimertinib. What should we do proactively to keep these patients on treatment longer?

Dupille: Education is so important—it’s about preparation and being aware of potential adverse effects [AEs] ahead of time. With osimertinib, we know patients could get diarrhea, and they could get a rash. I ask patients to get antidiarrheals and an electrolyte supplement in the home before they need them, and make sure they have over-the-counter hydrocortisone, because that’s something we’d recommend if a rash develops. The education we provide initially is overwhelming, and patients aren’t going to retain it all in one sitting, so it’s a continuum throughout treatment. If a patient calls with 3 episodes of diarrhea and doesn’t have loperamide in the house, that’s going to prolong the AE and can lead to dehydration or electrolyte imbalances.

Dennis: With osimertinib, having loperamide in the home before starting treatment is important. If we’re adding chemotherapy to osimertinib, we need to educate on depletion of folic acid and vitamin B12. We need to make sure that they have nausea medications in their home, and that they know how to utilize them on a rotational basis, or to call if their symptoms are unmanageable. If patients are on amivantamab plus lazertinib, we’re educating on skin protection, [sun protection factor] SPF, chlorhexidine washes, and prophylactically starting doxycycline or minocycline before therapy begins.

Preventing and Managing Osimertinib-Related Dermatologic Toxicity

Dennis: Where do you land on prophylaxis-first vs treating on appearance for dermatologic AEs, and how does that differ across regimens?

McDonald: The approach depends on the regimen. For osimertinib alone, the dermatologic toxicity is generally more modest, but we still do a baseline skincare assessment and education. Most of the time we see an acneiform rash, typically on the scalp, central face, upper chest, and back. Once the rash develops, I’m aggressive with a regimen: a gentle, unscented face wash twice daily, an unscented moisturizer, and topical clindamycin lotion—I find the gel too drying. If it’s not improving, we move to an oral antibiotic like doxycycline, and I don’t hesitate to refer to dermatology early if patients aren’t responding to simple regimens.

The other thing I see is paronychia, which usually starts 1 to 3 months after starting treatment. I use diluted bleach-and-water soaks for these patients. I also look at zinc levels—there’s evidence to suggest zinc plays a role in EGFR activation and expression, so zinc supplementation has been used to help improve rash in patients with low zinc levels. If you start patients on zinc consistently, you should also check a copper level, given how zinc and copper interact.

Dennis: The big message for patients is that we expect this—we expect rashes more with amivantamab plus lazertinib than with osimertinib, which is why we’re so preventive with the [phase 3 COCOON trial (NCT06120140)] regimen for that combination, but we do expect it either way. Management is key so we can keep patients on treatment as long as possible without dose reductions or delays.

McDonald: Switching to amivantamab and lazertinib, we need to be much more proactive because the dermatologic toxicity can be more severe. We all should be using prophylactic treatment from day 1 with the COCOON approach.⁴ That starts 2 days before the first infusion with dexamethasone; moisturizers and emollients; sun protection with at least SPF 30; and aggressive scalp and nail prevention to prevent paronychia, including clobetasol solution, skin glue for fissures or cracked skin, and chlorhexidine soaks for fingers and toenails. I keep these patients prophylactically on doxycycline and a hydrocortisone cream for about 12 weeks, then taper before stopping, and resume if the rash flares. The take-home for nursing anywhere: don’t wait until the rash becomes significant. Get patients in early because we want to prevent toxicity from driving dose interruptions and discontinuation.

Recognizing Interstitial Lung Disease and Grading Toxicity

Dennis: Interstitial lung disease [ILD] is an active concern across osimertinib-based and amivantamab-based regimen, and is a toxicity we worry about. How do you recognize it early?

McDonald: The risk of pneumonitis or ILD with osimertinib is about 4%; with amivantamab, it’s a little over 3%, depending on the regimen. The biggest role nursing has is recognizing changes early and getting patients into clinic for a workup.

We’re asking about new or worsening symptoms, fevers, and hypoxia, then working through the differential: Could this be drug-induced ILD? An infection? Disease progression? A blood clot, given the VTE risk with some regimens? For patients who’ve had radiation, could this be radiation pneumonitis? Timing matters—we get imaging and look at whether changes correspond to the radiation field. Early recognition is what prevents delayed diagnosis.

Dennis: Consistency is everything when it comes to grading CTCAEs across a team. How do you translate a grade into a hold, dose reduction, or continue decision, like, for instance, reducing osimertinib to 40 mg?

McDonald: We use the CTCAE grading scale as a reference, which gives the whole multidisciplinary team a common language, rather than someone documenting a “bad rash” or “severe diarrhea.” Grade 1 toxicity is often managed with supportive care and we continue treatment. Grade 2 requires more aggressive intervention and possibly a hold. Grade 3 or higher often means a treatment interruption and consideration of dose reduction. The specific toxicity matters as much as the grade: with osimertinib, a significant grade 3 toxicity may mean holding treatment and restarting at 40 mg once symptoms improve, whereas with amivantamab, grade 3 dermatologic toxicity generally means holding and being aggressive before resuming. ILD is the exception—if we suspect pneumonitis, we don’t wait for it to become high grade; we hold and evaluate at first concern.

Managing Diarrhea and Nutrition During Long-Term Osimertinib Therapy

Dennis: On the gastrointestinal side, can you walk us through your practical approach to diarrhea, stomatitis prevention, and nutrition, including your diarrhea algorithm? When do you bring in dietitian support?

Dupille: If someone calls with diarrhea, I want to know if they’re on any laxatives or stool softeners we should stop, and what they’ve been eating—a lot of people keep eating their normal diet and need to steer toward a bland diet with more fluids. For mild cases, 1 to 2 episodes, we recommend over-the-counter loperamide, plus increased fluids and a [bananas, rice, applesauce, toast] BRAT diet. If diarrhea isn’t resolving, I’ll let the provider know so they can consider something stronger. If someone is having 5 to 7 episodes and feeling weak and fatigued, we’re bringing them in the same day for labs, hydration, and evaluation. We teach a clear ceiling—no more than about 8 tablets in 24 hours—and patients need to call, even after hours, if they hit that mark.

Dennis: In our clinic, we teach loperamide at first watery stool, then a maximum of 6 doses in a day before they call, even after hours. It’s important they call so electrolytes, which some of these medications can already decrease, stay within normal limits. We have oncology-certified dietitians, and I love getting them involved early, since a lot of these patients come in with unintentional weight loss.

Patient Case: Intensifying Beyond Single-Agent Osimertinib

Dennis: A 58-year-old woman with newly diagnosed EGFR exon 19 deletion metastatic lung adenocarcinoma has high disease burden, and her team is intensifying first-line therapy beyond single-agent osimertinib. She was drawn to a “chemotherapy-free” option she read about online and is anxious about hair loss and nausea. The team is weighing osimertinib plus platinum chemotherapy and pemetrexed against amivantamab plus lazertinib. If the team selects osimertinib plus platinum and pemetrexed, what does your upfront toxicity-prevention and monitoring plan look like?

McDonald: Before we even get into toxicity monitoring, we have to acknowledge the emotional shift for this patient. She may have been thinking, “I have an EGFR mutation, I’m going to take osimertinib,” expecting relatively infrequent visits, and now we’re telling her we’re adding systemic chemotherapy. She’s coming into an infusion center at least every 3 weeks, having more frequent lab work, and facing chemotherapy-related AEs she has preconceived notions about. From there, we’re proactive about prevention: monitoring her counts and renal function, making sure she’s taking folic acid with the pemetrexed regimen and getting her vitamin B12 injection every 9 weeks, building a good antiemetic plan, and discussing cumulative fatigue.

The nursing role isn’t just safely delivering the regimen; it’s helping the patient adjust emotionally and practically to a plan that looks very different than what she expected. These patients are tech-savvy; they’re reading up on their disease and coming in well informed, so we need to be prepared for that. Beyond the physical side, there’s the practical burden: transportation, financial toxicity, work, and caregiving obligations. We need a multidisciplinary approach with social work and dietitian support for any unintentional weight loss.

Dennis: If the team instead selects amivantamab plus lazertinib, what does the parallel nursing preparation look like?

McDonald: There’s a high risk of an infusion-related reaction the first-time patients receive amivantamab—anecdotally, close to 65% to 66%, so I prepare everybody for a potential reaction. We use the COCOON approach, with dexamethasone starting 2 days before the regimen, and the first dose is split across 2 consecutive days. If a patient has any reaction, we stop the infusion and have them come back the next day rather than rechallenging that same day. With the subcutaneous formulation of amivantamab, that infusion-reaction risk drops from around 66% to about 13%, saving roughly 2 hours of chair time, though patients still need 2 hours of monitoring afterward and the same dermatologic prophylaxis. With lazertinib, we also need at least 4 months of anticoagulation for VTE prophylaxis, since these patients are at higher risk for blood clots earlier in treatment.

Dupille: We provide a follow-up call 24 hours after the first treatment to check for residual AEs, reiterate anticoagulation adherence and bleeding precautions, and confirm they’re taking doxycycline as prescribed.

Dennis: As we discussed, this patient specifically fears chemotherapy, and “chemotherapy-free” is a phrase we hear a lot in clinic. It’s important that patients know chemotherapy-free doesn’t mean toxicity-free. Each of these regimens comes with different toxicities and different management, and the goal is to keep patients on treatment as long as possible with the best outcome and quality of life.

Patient Case: Sustaining Adherence During Long-Term Single-Agent Osimertinib

Dennis: A 70-year-old man has been on single-agent osimertinib for 26 months for EGFR L858R metastatic NSCLC, with an excellent, durable response. He’s managed at a community clinic without an infusion touchpoint, has chronic grade 1 to 2 dermatologic toxicity and fatigue, has quietly skipped doses when his rash flares, and recently said he’s “tired of taking pills forever.” When there’s no infusion visit to anchor contact, how do you manage oral oncolytic adherence?

Dupille: After initial teaching, we usually call within 2 to 5 days to check on adherence. Since this patient is skipping doses when his rash flares, the education is that there are remedies for the rash, and it doesn’t mean he has to stop the medication. I’d get permission to loop in a caregiver and come up with a plan: reminders, alarms, over-the-counter hydrocortisone if he’s itching, and a pill diary. A social worker can help get to the bottom of why he’s stopping over what sounds like a mild rash; there might be more to it. If nonadherence continues, that might warrant a weekly phone call or home health nursing for medication teaching.

Dennis: We also need to look at what caregivers he has at home and educate him on the alternative options and their trade-offs if he did stop. Cost and access are also part of adherence. What does specialty pharmacy coordination and financial-toxicity screening look like in your practice?

Dupille: We have a dedicated team that manages all of that, they work miracles. A prescription is written, it automatically routes to our pharmacy team for prior authorization, and if there’s a copayment of $5000 that no one can afford, we have a resource who gets that down, sometimes to zero.

McDonald: We’re lucky with our infrastructure, but in community practices, this can be a real challenge. It can be hard to even identify who the prior authorization team is, and it can fall back on nursing to fight for copay assistance or find grant and free-drug programs.

Dupille: Letting the patient know the process, that a $3000 copayment looks scary, but we’re going to figure it out, alleviates a lot of anticipatory anxiety about starting treatment.

Osimertinib in Special Settings: Consolidation, CNS Disease, and Survivorship

Dennis: In the stage III setting, osimertinib is given as consolidation after chemoradiation, per the phase 3 LAURA trial (NCT03521154).⁵ How do you sort out overlapping toxicity in these patients, particularly distinguishing radiation pneumonitis from drug-induced ILD, and how do you manage esophagitis and the layered symptom burden they carry?

McDonald: There’s so much overlap. These patients may already have a cough, dyspnea, fatigue, or esophagitis coming out of chemoradiation, so a good baseline becomes important. If respiratory symptoms worsen, we’re thinking about radiation pneumonitis, with osimertinib-related ILD on the differential, along with infection or early disease progression. Timing matters; we get imaging and look at whether changes correspond to the radiation field. Our biggest role is recognizing that change early and initiating the workup. We also can’t overlook esophagitis: we’re assessing pain, swallowing ability, and hydration, monitoring weight, and involving our dietitian, since these patients can carry a significant cumulative symptom burden.

Dennis: Many of these patients also have CNS disease or brain metastases. What does symptom monitoring look like there, and how do you manage steroid tapers?

McDonald: I want a clear neurologic baseline, with the caregiver involved, so we know what changes to watch for: new headache, focal weakness, balance or vision changes, confusion, or, rarely, seizure activity. The caregiver often catches what the patient minimizes. Steroid tapers are another important touchpoint; patients need a clear, written schedule and should know not to adjust it on their own. As we taper, we’re watching for recurrent neurologic symptoms, but also monitoring the consequences of prolonged steroids: hyperglycemia, insomnia, mood changes, and increased infection risk.

Dennis: Patients living long on targeted therapy face survivorship-style issues even while on treatment. How do you address chronic toxicity, fatigue, and goals-of-care conversations for someone who may be on therapy for years?

Dupille: It’s challenging, always taking a pill, always coming in for therapy. We bring in social work, and at Dana-Farber we have a sexual health program patients can be referred to, since we have a lot of young patients with lung cancer. It’s not always an easy subject for a patient to raise with their provider. It’s about probing gently to find out what’s behind how a patient is feeling, then referring appropriately.

McDonald: The biggest takeaway is that we need to listen to our patients. Their biggest struggle isn’t always something we can see on an exam or capture in a lab value—it may be treatment fatigue, emotional burden, or financial toxicity. The patient is part of the team; it’s a partnership between the patient, the caregiver, and everyone on their care team.

References

1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer. Version 2026. Accessed September 22, 2026. https://tinyurl.com/p4bkf8zp
2. Jänne PA, Planchard D, Kobayashi K, et al. Survival with osimertinib plus chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2026;394(1):27-38. doi:10.1056/NEJMoa2510308
3. Yang JC-H, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001
4. Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530.
5. Lu S, Kato T, Dong X, et al; LAURA Trial Investigators. Osimertinib after chemoradiotherapy in stage III EGFR-mutated NSCLC. N Engl J Med. 2024;391(7):585-597. doi:10.1056/NEJMoa2402614