Osimertinib Plus Platinum-Based Chemotherapy Approved for Locally Advanced or Metastatic Non–Small Cell Lung Cancer

The FDA has granted approval to osimertinib (Tagrisso®, AstraZeneca Pharmaceuticals LP) with platinum-based chemotherapy for patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. 

Why it matters: “Osimertinib is a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) that is selective for EGFR-TKI­–sensitizing and EGFR T790M resistance mutations,” wrote David Planchard, MD, PhD, Head of the Thoracic Cancer Group in the Department of Medicine at Gustave Roussy, in Villejuif, France, and colleagues, in their published results of the FLAURA2 trial (NCT04035486), on which approval was based. “Evidence suggests that the addition of chemotherapy may extend the benefits of EGFR-TKI therapy.”

What they studied: Efficacy was measured in the phase 3, open-label trial in which 557 patients were randomized 1:1 to receive either osimertinib plus platinum-based chemotherapy or osimertinib monotherapy. Key inclusion criteria required patients to have locally advanced or metastatic NSCLC harboring an EGFR exon 19 deletion or exon 21 L858R mutation, and no prior systemic therapy for advanced disease.

The primary efficacy outcome studied was progression-free survival, with a key secondary end point of overall survival.

What they found: Progression-free survival garnered a statistically significant improvement in those receiving osimertinib plus platinum-based chemotherapy compared with osimertinib monotherapy. The median progression-free survival was 25.5 months in the osimertinib plus platinum-based chemotherapy arm compared with 16.7 months in the osimertinib monotherapy arm.

The overall survival results are currently immature with only 45% of prespecified deaths reported for the final analysis, but no trend towards a detriment have been observed.

Adverse events: The most common adverse events experienced by ≥20% of patients receiving osimertinib plus platinum-based chemotherapy were leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine. 

Conclusion: “First-line treatment with osimertinib-chemotherapy led to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC,” concluded Dr. Planchard and colleagues.

Instructions: The recommended dosage of osimertinib is 80 mg orally, once daily, with or without food, until disease progression or unacceptable toxicity. For pemetrexed and cisplatin or carboplatin dosage information, please refer to the prescribing information.

For More Information

Planchard D, Jänne PA, Cheng Y, et al (2023). Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med, 389(21):1935-1948. DOI:10.1056/NEJMoa2306434

Clinicaltrials.gov (2024). A study of osimertinib with or without chemotherapy as 1st line treatment in patients with mutated epidermal growth factor receptor non-small cell lung cancer (FLAURA2). NLM identifier: NCT04035486.

Tagrisso® (osimertinib) prescribing information (2024). AstraZeneca Pharmaceuticals LP. Available at: https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/52503580-1192-44f7-a05e-5743159ed19b/52503580-1192-44f7-a05e-5743159ed19b_viewable_rendition__v.pdf

US Food and Drug Administration (2024). FDA approves osimertinib with chemotherapy for EGFR-mutated non-small cell lung cancer. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer

Image credit: Yale Rosen. Licensed under CC BY-SA 2.0

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