Neoadjuvant Osimertinib With or Without Chemotherapy Improves Response in Resectable EGFRm NSCLC

Neoadjuvant osimertinib (Tagrisso; AstraZeneca) with or without chemotherapy (CT) demonstrated statistically meaningful improvements in major pathological response (MPR) rate over treatment with CT alone in patients with epidermal growth factor receptor-mutated (EGFRm) resectable non-small cell lung cancer (R-NSCLC), according to results from the phase 3 NeoADAURA clinical trial (NCT04351555) presented at the 2025 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.^1,2

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NeoADAURA Finds Improved Response With Osimertinib in Resectable Disease

The study enrolled a total of 358 patients, with individuals randomized 1:1:1 to receive neoadjuvant osimertinib 80 mg and cisplatin or carboplatin (n = 121), osimertinib monotherapy 80 mg (n = 117), or placebo plus CT (n = 120). All patients with R-NSCLC who completed surgery were offered adjuvant osimertinib. Overall, the investigators sought to measure MPR through a blinded central pathology review, with secondary end points including pathological complete response (pCR), event-free survival (EFS), and safety.¹

According to the investigators, the combination of osimertinib and CT elicited an MPR rate of 26%, while osimertinib monotherapy demonstrated a 25% MPR rate, both statistically significant improvements compared with placebo and CT (2%). Interim EFS—with 15% maturity—trended favorably towards osimertinib with CT and osimertinib monotherapy versus placebo and CT, the investigators found.¹

Notably, over 80% of patients in each arm received adjuvant osimertinib. Regarding the safety of patients during the neoadjuvant period of treatment, grade 3 or higher all-cause adverse events (AEs) and AEs leading to treatment discontinuation of any kind were observed at a higher rate in patients receiving CT, either with placebo or osimertinib, with a significantly higher rate in patients receiving both osimertinib and CT. However, no patients died within 30 days of completing surgery, a critical benchmark of treatment efficacy.¹

ADAURA Trial Solidified Osimertinib as Standard Care in EGFRm NSCLC

Osimertinib has been deemed a standard-of-care treatment for resected EGFRm stage IB to IIIA NSCLC. This is based in part on the results of the double-blind, phase 3 ADAURA clinical trial (NCT02511106), which randomly assigned 682 patients to receive either osimertinib (n = 339) or placebo (n = 343) for 3 years in an analysis of disease-free survival among those with stage II to IIIa disease. At a follow-up of 24 months, 90% of patients at this advanced disease stage in the osimertinib group (95% CI, 84%–93%) and 44% in the placebo group (95% CI, 37%–51%) were alive and disease-free (hazard ratio [HR]: 0.17 [99.06% CI, 0.11–0.26]; P < .001).^3,4

Examination of the overall population found that 89% of osimertinib-treated patients and 52% of placebo-treated patients were alive and disease-free at 24 months (HR: 0.20; [99.12%, 0.14—0.30]; P < .001), according to the investigators. In a critical development, at the 24-month follow-up point, 98% of patients in the osimertinib group were alive and did not have central nervous system disease, compared with 85% of patients in the placebo group (HR: 0.18; 95% CI, 0.10–0.33). At the time of reporting, overall survival data were immature.3

Considerations for Pharmacists

The results of ADAURA and NeoADAURA provide comprehensive backing to the use of osimertinib in patients with NSCLC, both as adjuvant and neoadjuvant treatment. For patients with resectable disease, care providers must help patients navigate treatment protocols and adhere to therapy. Pharmacists play a critical role in providing medication education to patients and specialized counseling for treatment transitions, especially when switching to or from osimertinib to other therapies. Furthermore, they are essential in managing AEs and prescribing appropriate treatments to manage them if they occur with osimertinib treatment.⁵

REFERENCES

1. Chaft J, Weder W, He J, et al. Neoadjuvant (neoadj) osimertinib (osi) ± chemotherapy (CT) vs CT alone in resectable (R) epidermal growth factor receptor-mutated (EGFRm) NSCLC: NeoADAURA. J Clin Oncol. 2025;43(16). doi:10.1200/JCO.2025.43.16_suppl.8001. Presented at: 2025 American Society of Clinical Oncology Annual Meeting; May 30 to June 3, 2025; Chicago, Illinois.

2. A Study of Osimertinib With or Without Chemotherapy Versus Chemotherapy Alone as Neoadjuvant Therapy for Patients With EGFRm Positive Resectable Non-Small Cell Lung Cancer (NeoADAURA). National Library of Medicine. ClinicalTrials.gov identifier: NCT04351555. Updated May 23, 2025. Accessed June 4, 2025. https://clinicaltrials.gov/study/NCT04351555

3. Wu Y, Tsuboi M, He J, et al. Osimertinib in resected EGFR-mutated non-small-cell lung cancer. N Engl J Med. 2020;383(18):1711-1723. doi:10.1056/NEJMoa2027071

4. AZD9291 Versus Placebo in Patients With Stage IB-IIIA Non-small Cell Lung Carcinoma, Following Complete Tumour Resection With or Without Adjuvant Chemotherapy. (ADAURA). ClinicalTrials.gov identifier: NCT02511106. Updated May 25, 2025. Accessed June 4, 2025. https://clinicaltrials.gov/study/NCT02511106

5. Chang C. Enhancing patient care through multidisciplinary team collaboration in management of NSCLC. Pharmacy Times. Published May 2, 2025. Accessed June 4, 2025. https://www.pharmacytimes.com/view/enhancing-patient-care-through-multidisciplinary-team-collaboration-in-management-of-nsclc