Opinion: Osimertinib Plus Chemo May Enhance Outcomes in Metastatic EGFR-Mutated Lung Cancer

Amanda Brink, DNP, APRN, FNP-BC, AOCNP

In the United States, lung cancer holds the unfortunate distinction of being the second most frequently diagnosed cancer among both men and women, following prostate cancer for men and breast cancer for women. Projections for 2024 indicate that there will be over 230,000 new cases of lung cancer, with more than 125,000 individuals succumbing to the disease.¹

Targeted therapies guided by molecular diagnostics have become a standard approach in treating patients with non-small cell lung cancer (NSCLC). Patients diagnosed with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation can be treated with a class of medications known as tyrosine kinase inhibitors (TKIs), some of which specifically target EGFR.² These TKIs have been shown to have superior effectiveness compared to first-line platinum-based chemotherapy in patients with advanced NSCLC with an EGFR mutation.³

EGRF-positive lung cancer represents about 10-15% of lung cancer diagnoses in the United States.4 It is more common in patients of Asian descent2 and those with little to no smoking history.⁴

First-generation TKIs targeting EGFR include gefitinib and erlotinib, while afatinib is a second-generation TKI targeting EGFR. Despite a notably high objective response rate (ORR) of 60–70%, most patients treated with these agents ultimately develop resistance, with progression-free survival (PFS) averaging 9 to 15 months. Resistance commonly arises from the T790M mutation in EGFR exon 20. Third-generation TKIs, including osimertinib (Tagrisso), target both the EGFR mutations and the T790M-resistance mutation.³

Unfortunately, patients with lung cancer harboring an EGFR or anaplastic lymphoma kinase (ALK) mutation are more commonly diagnosed with brain metastasis than other patients with NSCLC, with estimates as high as 70%.⁵ Therefore, it is crucial for EGFR TKIs to effectively treat a patient’s brain metastasis along with other areas of systemic disease.

Central Nervous System Efficacy of Osimertinib in EGFR-Mutated NSCLC

In a clinical trial involving patients with untreated EGFR-mutated advanced NSCLC and baseline central nervous system (CNS) metastases, osimertinib demonstrated a 52% reduction in the risk of CNS progression or death compared to erlotinib (Tarceva) and gefitinib (Iressa). Despite the known benefit of osimertinib therapy, questions persist regarding whether adding chemotherapy to osimertinib may further enhance outcomes compared with osimertinib monotherapy, especially in patients with baseline CNS metastases.⁶

Jänne et al.⁶ conducted a phase 3, international open-label, randomized clinical trial in untreated patients with EGFR-mutated advanced NSCLC. Eligible patients were randomly assigned 1:1 to receive either osimertinib plus platinum-pemetrexed chemotherapy or osimertinib monotherapy.

A total of 557 patients participated in the study, all of whom underwent baseline brain imaging before starting treatment. Baseline characteristics were balanced between the groups. Of the 222 patients with baseline CNS disease, the combination of osimertinib and chemotherapy yielded a 24-month CNS PFS rate of 74% compared to 54% with chemotherapy alone. However, the observed difference did not reach statistical significance (HR, 0.58; 95% CI, 0.33-1.01). Interestingly, the number of patients who achieved a complete response in the CNS was higher in the combination arm (59%) compared to the monotherapy arm (43%).

Notably, among the limited number of patients with baseline leptomeningeal metastases, 8 out of 13 patients in the combination treatment group remained alive and free from CNS progression, compared to none in the monotherapy arm.

Findings across the entire study population, including those with and without CNS disease, were also favorable for combination therapy, with a trend towards enhanced overall survival.

Nursing Considerations

After receiving a cancer diagnosis, patients are understandably eager to commence anti-cancer treatment promptly. However, in the case of patients newly diagnosed with lung cancer, it is crucial to wait until biomarker testing results are available before determining the most suitable treatment approach. When patients inquire about the timing of treatment initiation with their oncology care team, oncology nurses can provide education regarding the treatment implications associated with obtaining biomarker results.

Patients may also experience difficulty tolerating a brain MRI due to claustrophobia. Therefore, it is crucial to effectively communicate to patients the significance of undergoing brain imaging to monitor for brain metastasis in specific cancer types, such as EGFR-mutated NSCLC. When patients know the rationale behind these tests, they are often more inclined to have them done.

In conclusion, lung cancer remains a significant health concern in the United States, with a high incidence and mortality rate projected for 2024. Targeted therapies guided by molecular diagnostics, particularly for EGFR-mutated NSCLC, have revolutionized treatment approaches and improved outcomes for patients. Oncology nurses play a crucial role in patient education and support throughout the treatment journey, emphasizing the importance of biomarker testing and brain imaging for comprehensive disease management. By continuing to develop next-generation therapies and exploring combination approaches, we can aim for improved outcomes in patients with EGFR-mutated NSCLC and CNS metastases.

References

1. Lung cancer statistics. Lung Cancer Statistics. Accessed April 7, 2024. https://www.cancer.org/cancer/types/lung-cancer/about/key-statistics.html
2. Shim HS, Choi YL, Kim L, et al. Molecular Testing of Lung Cancers. J Pathol Transl Med. 2017;51(3):242-254. doi:10.4132/jptm.2017.04.10
3. Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E, Tiseo M. Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 2019;121(9):725-737. doi:10.1038/s41416-019-0573-8
4. EGFR and lung cancer. EGFR and Lung Cancer. Accessed April 7, 2024. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr
5. Kelly WJ, Shah NJ, Subramaniam DS. Management of Brain Metastases in Epidermal Growth Factor Receptor Mutant Non-Small-Cell Lung Cancer. Front Oncol. 2018;8:208. Published 2018 Jul 3. doi:10.3389/fonc.2018.00208
6. Jänne PA, Planchard D, Kobayashi K, et al. CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer. J Clin Oncol. 2024;42(7):808-820. doi:10.1200/JCO.23.02219