Osimertinib plus chemotherapy improves PFS in advanced EGFR+ NSCLC

The combination of osimertinib (Tagrisso) and platinum-based chemotherapy led to a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared with osimertinib alone in patients with locally advanced or non-small cell lung cancer (NSCLC). metastatic EGFR extension mutations, according to the final analysis of the primary endpoint of the Phase 3 FLAURA2 study (NCT04035486).¹

Notably, overall survival (OS) data were immature at the time of this analysis; will be formally evaluated in the future. Full data from the analysis will be presented at an upcoming medical meeting and shared with global health authorities.

As a global standard of care for EGFR extensionwith mutant NSCLC, osimertinib monotherapy has transformed the treatment landscape by offering many patients the opportunity for improved survival, said Pasi A. Jnne, MD, PhD, physician oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 study, in a news publication. FLAURA2 provides compelling evidence that adding chemotherapy to osimertinib may provide a new option for patients and clinicians that further improves outcomes compared to osimertinib alone and, as such, may further delay treatment resistance and disease progression.

The global, randomized, open-label, multicenter study FLAURA2 enrolled 586 previously untreated patients 18 years of age or older with pathologically confirmed, non-squamous, EGFR extension– Locally advanced (stage IIIB to IIIC) or metastatic (stage IV) mutant NSCLC that was not amenable to curative surgery or radiation therapy.² Patients were also required to have a World Health Organization performance status of 0 or 1 at screening and a life expectancy greater than 12 weeks.

The main exclusion criteria included spinal cord compression, unstable brain metastases, a history of interstitial lung disease, any evidence of severe or uncontrolled systemic disease, QT prolongation, or inadequate bone marrow reserve or organ function. Patients with stable brain metastases who completed definitive therapy, were off steroid therapy, and had stable neurologic status were allowed to enroll.

Patients were randomly assigned to receive oral osimertinib 80 mg once daily alone or in combination with 500 mg/m² of pemetrexed plus 75 mg/m² of cisplatin or area under carboplatin curve 5 on day 1 of each 21-day cycle for a total of 4 cycles. In the experimental arm, maintenance therapy consisted of 80 mg osimertinib per day plus 500 mg/m² of pemetrexed once every 3 weeks.

PFS served as the primary endpoint. Secondary endpoints included OS, objective response rate, duration of response, depth of response, disease control rate, time to second progression, and quality of life.

Regarding safety, discontinuation rates due to adverse effects (AEs) were consistent with the established profiles of each drug.

In previously reported data from 30 patients included in the safety run-in portion of the study, adverse events occurred in 90% of all patients, including 100% of those receiving osimertinib plus carboplatin and pemetrexed (n = 15/15) and 80% of those treated with osimertinib plus cisplatin and pemetrexed (n = 12/15).³ The most common adverse events included constipation (60%) for patients receiving the carboplatin regimen and nausea (60%) for those receiving the cisplatin regimen.

Among all 30 patients, 20% had serious adverse events. No specific adverse event pattern led to dose modifications or discontinuations. One patient discontinued all study treatment due to pneumonia.

These significant FLAURA2 results show [osimertinib] it has the potential to offer patients on the frontline a new treatment option that can extend the time they live without their disease progressing, Susan Galbraith, executive vice president of oncology research and development at AstraZeneca, said in a news release.¹ This builds significantly on subsequent studies demonstrating improved clinical benefit with [osimertinib] in patients with EGFR extensionmutated lung cancer.

References

1. Tagrisso plus chemotherapy demonstrated a dramatic improvement in progression-free survival for patients with EGFR-mutant advanced lung cancer in the Phase III FLAURA2 study. Press release. AstraZeneca. May 17, 2023. Accessed May 17, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/
2. A study of osimertinib with or without chemotherapy as first-line treatment in patients with epidermal growth factor receptor mutant non-small cell lung cancer (FLAURA2). ClinicalTrials.gov. Updated May 6, 2023. Accessed May 17, 2023. https://clinicaltrials.gov/ct2/show/NCT04035486
3. Planchard D, Feng PH, Karaseva N, et al. Osimertinib plus platinum-pemetrexed in newly diagnosed epidermal growth factor receptor mutation-positive advanced/metastatic non-small cell lung cancer: safety run-in results from the FLAURA2 study. ESMO Open. 2021;6(5):100271. doi:10.1016/j.esmoop.2021.100271