Osimertinib Combo Significantly Prolongs Survival in Advanced EGFR+ NSCLC

"The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression," said trial investigator Pasi A. Jänne, MD, PhD.

Combining osimertinib (Tagrisso) with platinum-containing chemotherapy as frontline treatment produced a statistically significant and clinically meaningful overall survival (OS) improvement vs osimertinib alone among those with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR mutations, according to a press release on the final OS analysis of the phase 3 FLAURA2 trial (NCT04035486).1

In the final OS analysis, osimertinib/chemotherapy demonstrated a survival benefit that was consistent with results observed in the interim OS analysis, which investigators highlighted in March 2024.2 At the time of the interim OS analysis, the experimental combination yielded a favorable OS trend vs osimertinib monotherapy (HR, 0.75; 95% CI, 0.57-0.97). Results appeared to be consistent across prespecified subgroups based on characteristics such as race, sex, type of EGFR mutation, age at time of diagnosis, smoking history, performance status, and central nervous system metastases at baseline.

The latest OS results also build upon previously highlighted primary end point data, which investigators published in the New England Journal of Medicine in September 2023.3 These findings showed a median progression-free survival (PFS) of 25.5 months (95% CI, 24.7-not calculable) with osimertinib/chemotherapy vs 16.7 months (95% CI, 14.1-21.3) with osimertinib monotherapy based on investigator evaluation (HR, 0.62; 95% CI, 0.49-0.79; P < .0001).

In the updated OS analysis, the safety profile of osimertinib plus chemotherapy was comparable to prior reports of each individual agent. The rates of treatment discontinuation due to adverse effects (AEs) and on-target toxicities were low across both arms of the trial. The incidence of AEs was more frequent with osimertinib/chemotherapy due to chemotherapy-associated toxicity.

Investigators plan to present these results at a future medical meeting and share their findings with regulatory authorities across the world.

“When treating lung cancer, the aim is to both prolong survival and improve the patient experience, especially in [the first line], where treatment duration can be long and many patients remain active. These positive results support osimertinib, either as monotherapy or in combination with chemotherapy, as standard of care for patients with [first]-line advanced EGFR-mutated lung cancer and reinforce the meaningful benefit of the combination in the current clinical setting,” principal trial investigator Pasi A. Jänne, MD, PhD, senior vice president for translational medicine and thoracic medical oncologist at Dana-Farber Cancer Institute, stated in the press release.1 “The observed survival benefit is particularly impressive given that FLAURA2 did not impose any restrictions on the choice of subsequent treatment after disease progression.”

In the open-label, multicenter, international phase 3 FLAURA2 trial, 557 patients were randomly assigned 1:1 to receive osimertinib at 80 mg orally each day alone or in combination with chemotherapy. In the experimental arm, patients received pemetrexed at 500 mg/m2 or carboplatin area under the curve 5 every 3 weeks for 4 cycles followed by osimertinib and pemetrexed maintenance every 3 weeks.

The trial’s primary end point was PFS. Secondary end points included OS, duration of response, objective response rate, disease control rate, and time to first subsequent therapy.4

Patients 18 years or older with pathologically confirmed nonsquamous NSCLC and newly diagnosed locally advanced, metastatic, or recurrent disease not amenable to curative radiation or surgery were eligible for enrollment in the trial. Having a World Health Organization performance status of 0 to 1 at screening with no clinically significant deterioration in the 2 weeks prior to entry was another requirement for enrollment.

“These exciting [OS] results add to the extensive evidence supporting [osimertinib] as the backbone therapy in EGFR-mutated lung cancer, demonstrating that [osimertinib] plus chemotherapy can significantly extend survival in the [first]-line advanced setting, in addition to prior trials showing survival benefits as monotherapy in both early-stage and advanced disease,” Susan Galbraith, executive vice president of oncology hematology research and development at AstraZeneca, the developer of osimertinib, concluded.1

References

1. Tagrisso plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in overall survival in EGFR-mutated advanced lung cancer. News release. AstraZeneca. July 21, 2025. Accessed July 21, 2025. https://tinyurl.com/4rm89p33
2. Tagrisso with the addition of chemotherapy showed favourable trend in overall survival in EGFR-mutated advanced lung cancer with further follow up in FLAURA2 phase III trial. News release. AstraZeneca. March 21, 2024. Accessed July 21, 2025. https://tinyurl.com/yc4edum3
3. Planchard D, Jänne PA, Cheng Y, et al. Osimertinib with or without chemotherapy in EGFR-mutated advanced NSCLC. N Engl J Med. 2023;389(21):1935-1948. doi:10.1056/NEJMoa2306434
4. 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) (FLAURA2). ClinicalTrials.gov. Updated July 4, 2025. Accessed July 21, 2025. https://tinyurl.com/4kjpfu8a