Ask AI
Back Back
EGFR Therapy for NSCLC
Expert Nursing Perspectives on EGFR-Targeted Therapy for NSCLC

Released: January 07, 2026

Beth Sandy
Beth Sandy, MSN, CRNP, FAPO
Activity Information

Activity

Progress
1
Course Completed
Continue
Key Takeaways
  • Osimertinib remains a well-established standard for patients with metastatic EGFR-mutated NSCLC with common mutations; for patients who can tolerate treatment intensification, both osimertinib plus chemotherapy and amivantamab plus lazertinib offer meaningful improvements in survival compared with osimertinib alone.
  • With amivantamab plus lazertinib, the risk of higher-grade rash can be reduced using enhanced prophylactic strategies.
  • Osimertinib should not be given in a short time frame after immune checkpoint inhibitor therapy, as this can increase the risk of severe pneumonitis; patients should be evaluated with biomarker testing prior to starting immunotherapy.

In a recent local live meeting series, Beth Sandy, MSN, CRNP, FAPO, discussed contemporary use of EGFR-targeted therapy for non-small-cell lung cancer (NSCLC), highlighting key considerations for nurses and nurse practitioners and answering audience questions on these therapies. 

How has first-line treatment for metastatic EGFR-mutated NSCLC with common mutations evolved in recent years?
First-line therapy for metastatic NSCLC with an EGFR exon 19 deletion or exon 21 L858R mutation has evolved rapidly, with multiple effective options now available. Historically, EGFR TKIs replaced chemotherapy as preferred initial therapy because of improved disease control and tolerability. The FLAURA trial established osimertinib as the standard first-line EGFR TKI by demonstrating superior outcomes vs earlier-generation TKIs (erlotinib or gefitinib). Patients receiving osimertinib experienced longer progression-free survival (PFS) and improved overall survival (OS), even though many patients on the comparator arm later crossed over to receive osimertinib at progression. Osimertinib also showed an important advantage in safety, with fewer dermatologic toxicities, and strong activity in the central nervous system (CNS), which is particularly relevant given the high risk of brain metastases in EGFR-mutated disease. 

More recently, investigators tested whether combination treatments improve outcomes beyond osimertinib alone. The randomized FLAURA2 trial evaluated osimertinib plus platinum chemotherapy induction followed by osimertinib plus pemetrexed maintenance vs osimertinib monotherapy for treatment-naive advanced nonsquamous NSCLC with an EGFR exon 19 deletion or L858R mutation. Adding chemotherapy resulted in a substantial improvement in PFS, extending median PFS to more than 2 years and improving disease control in the CNS. Data presented recently also demonstrated an OS advantage, with 49% of patients alive at 4 years in the combination arm compared with just over 40% in the osimertinib alone arm. Median OS improved by approximately 10 months. Although these results support osimertinib plus chemotherapy as an effective intensification strategy, healthcare professionals (HCPs) must weigh the added benefit against chemotherapy-related toxicity and the logistical burden of frequent infusions and maintenance pemetrexed.

A second novel treatment approach was assessed in the randomized MARIPOSA trial, which compared amivantamab plus lazertinib vs osimertinib as first-line therapy for advanced NSCLC with an EGFR exon 19 deletion or L858R mutation. Amivantamab is a bispecific antibody targeting EGFR and MET, paired with lazertinib, an oral EGFR TKI. OS results favored the combination arm, with median OS not yet reached in the amivantamab plus lazertinib arm vs 36.7 months with osimertinib (HR: 0.75; P <.005). Because EGFR-mutated NSCLC has a high rate of CNS involvement, intracranial outcomes are clinically meaningful. MARIPOSA demonstrated numerically improved intracranial disease control with the combination regimen, with a greater proportion of patients free from brain progression at 3 years.

Osimertinib remains a well-established standard, particularly for patients prioritizing convenience and tolerability. For patients who can tolerate treatment intensification with additional medications, both osimertinib plus chemotherapy and amivantamab plus lazertinib offer meaningful improvements in survival compared with osimertinib alone. Treatment selection should incorporate patient-specific factors such as CNS disease risk, comorbidities, ability to attend infusion visits, and preferences regarding chemotherapy vs antibody-based therapy.

What are key adverse events and management strategies with the more recently approved agents used to treat EGFR-mutated NSCLC?
Rash is a common adverse event observed with EGFR-targeted therapies. With amivantamab plus lazertinib, the rate of grade 3/4 rash was 26% in clinical trials. Because of this, novel strategies were sought to reduce this rate of problematic rash with this combination. The randomized COCOON trial assessed enhanced dermatologic management for patients treated with amivantamab plus lazertinib. Patients were randomized to enhanced dermatologic management (oral doxycycline or minocycline twice daily with topical clindamycin lotion for the scalp and chlorhexidine solution for the nails) or standard dermatologic management. Grade ≥2 dermatologic adverse events were reduced from 77% with standard dermatologic management to 39% with the enhanced prophylaxis. This is something that we are doing now, and I can tell you from experience, this has dramatically reduced severe rashes by one half. These patients definitely do much better with that oral doxycycline on board. 

Notably, venous thromboembolism risk is also increased with amivantamab plus lazertinib vs osimertinib (overall 37% vs 9% in the phase III MARIPOSA trial). Prophylactic anticoagulation substantially reduces venous thromboembolisms and is now recommended for the initial 4 months of treatment with amivantamab plus lazertinib. We commonly use DOACs and it is recommended to use the prophylactic dose of anticoagulation, not the therapeutic dose, unless the patient already has a DVT or PE and thus should remain on therapeutic dose anticoagulation.

Recently, datopotamab deruxtecan, a TROP2-targeted antibody–drug conjugate, was approved by the FDA for treating locally advanced or metastatic EGFR-mutated NSCLC after prior EGFR-directed treatment and platinum-based chemotherapy. There are 3 key adverse events with this agent: oral mucositis, ocular events like dry eye, and interstitial lung disease. Stomatitis or mucositis occurred in approximately 70% of patients on clinical trials, with 9% grade ≥3. Ocular events occurred in 32% of patients, 3% of which were grade 3. For stomatitis, management recommendations include prophylactic mouthwash several times daily. The mouthwash is dexamethasone 0.1 mg/mL—do not use alcohol-based mouthwashes. For the ocular toxicities, we recommend that patients do not wear contact lenses while receiving therapy and use lubricating eye drops 4 times daily. Again, prevention is better here.

A word of caution regarding the use of immune checkpoint inhibitors and osimertinib: If HCPs give osimertinib in a short time frame (basically within 6 months) after immunotherapy, there is a significantly increased risk of severe pneumonitis, so this is not recommended. This is why HCPs should not give immunotherapy before knowing the biomarker status. If a patient has NSCLC with an EGFR mutation and will be considered for osimertinib, you risk severe pneumonitis if the patient has had immunotherapy within the past 6 months. It is very important to make sure a patient does not have NSCLC with an EGFR mutation before starting immunotherapy.

Your Thoughts
What challenges have you faced in using therapies for EGFR-mutated NSCLC? Please answer the polling question or leave a comment to join the discussion.

Continue

Poll

1.

On which of the following topics in therapeutic approaches for NSCLC with EGFR mutations would you most like further education?

Submit