Osimertinib Plus Chemotherapy Improves PFS in EGFR+ Advanced 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 metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to the final analysis of the primary end point of the phase 3 FLAURA2 trial (NCT04035486).¹

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

“As the global standard of care for EGFR-mutated NSCLC, osimertinib monotherapy has transformed the treatment landscape allowing many patients the opportunity to achieve improved survival,” Pasi A. Jänne, MD, PhD, medical oncologist at Dana-Farber Cancer Institute and principal investigator for the FLAURA2 trial, stated in a news release. “FLAURA2 provides compelling evidence that the addition of chemotherapy to osimertinib can provide a new option for patients and clinicians that further improves outcomes compared to osimertinib alone and as such, can further delay treatment resistance and disease progression.”

The randomized, open-label, multicenter, global FLAURA2 trial enrolled 586 previously untreated patients at least 18 years of age with pathologically confirmed, nonsquamous, EGFR-mutated locally advanced (stage IIIB to IIIC) or metastatic (stage IV) NSCLC who were not amenable to curative surgery or radiotherapy.² Patients were also required to have a World Health Organization performance status of 0 or 1 at screening and a life expectancy of more than 12 weeks.

Key exclusion criteria included spinal cord compression, unstable brain metastases, a history of interstitial lung disease, any evidence of severe or uncontrolled systemic diseases, QT prolongation, or inadequate bone marrow reserve or organ function. Patients with stable brain metastases who completed definitive therapy, were not on steroids, and had a stable neurological status were allowed to enroll.

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

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

Regarding safety, the rates of discontinuation 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 trial, AEs occurred in 90% of all patients, including 100% of those who received osimertinib plus carboplatin and pemetrexed (n = 15/15) and 80% of those given osimertinib plus cisplatin and pemetrexed (n = 12/15).³ The most common AEs included constipation (60%) for patients treated with the carboplatin regimen and nausea (60%) for those given the cisplatin regimen.

Among all 30 patients, 20% experienced serious AEs. No specific pattern of AEs led to dose modifications or discontinuations. One patient discontinued all study treatment due to pneumonitis.

“These significant FLAURA2 results show [osimertinib] has the potential to offer patients in the first-line setting 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 meaningfully builds on successive trials which have demonstrated improved clinical benefit with [osimertinib] in patients with EGFR-mutated lung cancer.”

References

1. Tagrisso plus chemotherapy demonstrated strong improvement in progression-free survival for patients with EGFR-mutated advanced lung cancer in FLAURA2 Phase III trial. News 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 1st line treatment in patients with mutated epidermal growth factor receptor 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 P-H, 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