Tagrisso and Chemotherapy: What the FLAURA2 Trial Showed

“Tagrisso and chemotherapy” refers to a specific regimen: osimertinib (Tagrisso) taken together with pemetrexed and platinum chemotherapy as the first treatment for advanced EGFR-mutated non-small cell lung cancer (NSCLC). The evidence comes from one trial, FLAURA2. This guide explains how it was designed, what it reported on progression-free survival and overall survival, what the safety data show, and why the regimen matters competitively. It describes published results and does not recommend any treatment.

Updated November 4, 2026.

What was the FLAURA2 trial?

FLAURA2 (NCT04035486) is an international, open-label phase 3 trial funded by AstraZeneca. It randomly assigned 557 patients with EGFR exon 19 deletion or L858R mutation advanced NSCLC, who had not yet received treatment for advanced disease, in a 1:1 ratio to osimertinib 80 mg daily plus pemetrexed with cisplatin or carboplatin, or to osimertinib alone. The primary endpoint was investigator-assessed progression-free survival (PFS) (NEJM 2023).

The comparison is deliberate: the control arm is osimertinib itself, the current reference first-line drug. For how osimertinib did against older drugs, see Tagrisso vs Tarceva and Iressa.

What did FLAURA2 show on progression-free survival?

The FDA’s approval notice reports median PFS of 25.5 months with osimertinib plus chemotherapy vs 16.7 months with osimertinib alone (hazard ratio 0.62; 95% CI 0.49 to 0.79; P under 0.0001) (FDA). A coverage report by Healio adds that blinded central review showed a 9.5-month difference in median PFS, compared with 8.8 months by investigator assessment (Healio).

Did Tagrisso plus chemotherapy improve overall survival?

At the time of FDA approval, overall survival (OS) was immature, with 45% of the planned deaths reported, and the FDA noted no trend toward detriment. The final OS analysis was presented at the IASLC World Conference on Lung Cancer in September 2025. Median OS was 47.5 months with the combination vs 37.6 months with osimertinib alone (hazard ratio 0.77; 95% CI 0.61 to 0.96; P = 0.02) (ASCO Post). The trial was funded by AstraZeneca, and the hub article on Tagrisso also records this final OS result.

Two cautions apply. FLAURA2 was open-label, so patients and doctors knew the assigned arm. And OS followed many later treatments, which complicates any reading of the survival gap.

What are the safety and tolerability findings?

Adding chemotherapy adds chemotherapy side effects. The FDA lists adverse reactions occurring in at least 20% of patients on the combination, including low blood counts (leukopenia, neutropenia, thrombocytopenia, lymphopenia), rash, diarrhea, stomatitis, nail toxicity, dry skin and increased blood creatinine. Healio’s report of the primary analysis gives grade 3 or higher adverse events of 64% with the combination vs 27% with osimertinib alone, and adverse events leading to discontinuation of 11% vs 6%. FLAURA2 investigators have attributed the higher rate of grade 3 or higher events to well-recognized chemotherapy-related adverse events (ESMO abstract). Safety percentages can shift with longer follow-up, so the final-analysis figures in the NEJM paper are the ones to check.

The regimen also changes the logistics of treatment: osimertinib is a daily pill continued until progression or unacceptable toxicity per the FDA label, while the chemotherapy is given by infusion in cycles. The trial used pemetrexed plus either cisplatin or carboplatin.

How does it compare with osimertinib alone?

In plain terms, the trial reported that adding platinum-pemetrexed chemotherapy to osimertinib kept the disease from progressing for a median of about 8.8 months longer (investigator-assessed: 25.5 vs 16.7 months) and was followed by a median survival of about 9.9 months longer (47.5 vs 37.6 months). The price, in the trial, was more treatment-related toxicity and added chemotherapy infusions. Whether those trade-offs favor one regimen depends on the patient and is a clinical judgment outside the scope of this article. What the data establish is the size of the differences in this one randomized trial; what they do not establish is how the regimens compare in groups the trial did not enroll, such as people with other EGFR mutation types.

When was the combination approved?

On February 16, 2024 the FDA approved osimertinib with platinum-based chemotherapy for locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations, based on FLAURA2 (FDA). Osimertinib monotherapy remains approved as well, so FLAURA2 broadened the label rather than replacing it.

Why does Tagrisso plus chemotherapy matter competitively?

Several points matter to analysts:

• It raises the bar for the control arm. New first-line EGFR regimens must now consider whether to beat osimertinib alone, osimertinib plus chemotherapy, or both.
• It puts a survival result behind a combination. The hub article describes the MARIPOSA trial of amivantamab plus lazertinib, which reported an OS advantage over osimertinib alone with more serious adverse events (grade 3 or higher: 80% vs 52% in the figures the hub cites). Cross-trial comparison with FLAURA2 is unreliable because the designs, populations and control arms differ.
• It extends the franchise. The regimen keeps osimertinib as the targeted backbone, which is relevant to lifecycle thinking for the Tagrisso brand.
• It sharpens the tolerability trade-off. The reported gains in PFS and OS come with higher rates of serious adverse events and more discontinuations, which is why tolerability is now a central selling point for competing regimens. For what follows progression, see what comes after Tagrisso.

For the stage-by-stage trial map, see the FLAURA, ADAURA and LAURA guide, and for how to check arms and endpoints in trial records, the ClinicalTrials.gov reading guide.

Next step

Teams weighing how first-line EGFR combinations change their competitive set can look at Oncology Resource Group’s advisory page.

This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.