Amongst sufferers with EGFR-mutated non-small cell lung most cancers, together with these with poor prognostic components, remedy with Tagrisso (osimertinib) with platinum-based chemotherapy and pemetrexed was related to an enchancment in survival in contrast with Tagrisso alone throughout subgroups, based on knowledge from an exploratory evaluation of the part 3 FLAURA2 trial.
Beforehand reported knowledge from the trial’s last general survival (OS) evaluation confirmed that sufferers handled with Tagrisso plus chemotherapy (279 sufferers) achieved a median OS of 47.5 months versus 37.6 months for these handled with Tagrisso alone (278 sufferers).
The exploratory evaluation, which was introduced on the 2025 ESMO Congress, examined outcomes for sufferers primarily based on the next six prognostic components:
- Central nervous system (CNS) metastases
- Bone metastases
- Liver metastases
- EGFR mutation standing
- TP53 standing
- Plasma EGFR mutations in circulating tumor DNA
“Hazard ratios for OS favored the mix arm, no matter baseline prognostic components, and have been per the general inhabitants,” lead examine creator Dr. Pasi A. Jänne stated in a presentation of the information. Jänne is a senior doctor, senior vp for Translational Drugs, director of the Belfer Heart for Utilized Most cancers Science, director of the Chen-Huang Heart for EGFR Mutant Lung Cancers, and the David M. Livingston, MD, Chair at Dana-Farber Most cancers Institute, in addition to a professor of medication at Harvard Medical College in Boston.
What Have been the FLAURA2 OS Outcomes by Prognostic Subgroup?
In sufferers harboring CNS metastases at baseline, the median OS was 40.9 months for Tagrisso plus chemotherapy (116 sufferers) in contrast with 29.7 months for Tagrisso monotherapy (110 sufferers). The three-year OS charges on this subgroup have been 57% and 40%, respectively. In sufferers with out CNS metastases at baseline, the median OS was not reached for Tagrisso plus chemotherapy (163 sufferers) versus 43.9 months for Tagrisso alone (168 sufferers).
Sufferers harboring EGFR exon 21 L858R mutations handled with Tagrisso plus chemotherapy (106 sufferers) achieved a median OS of 38.1 months versus 32.4 months for Tagrisso alone (107 sufferers). The respective three-year OS charges have been 54% and 42%. In sufferers harboring EGFR exon 19 deletions, the median OS was not reached for Tagrisso plus chemotherapy (172 sufferers) versus 43 months for Tagrisso alone (169 sufferers).
Amongst sufferers with EGFR mutations detected in plasma ctDNA, the median OS was 38.4 months for Tagrisso plus chemotherapy (148 sufferers) versus 32.5 months for Tagrisso monotherapy (161 sufferers). The three-year OS charges on this subgroup have been 53% for Tagrisso plus chemotherapy versus 42% for Tagrisso alone. In sufferers with out EGFR mutations detected in plasma ctDNA, the median OS was not reached and never reached for the mix (65 sufferers) and Tagrisso monotherapy (48 sufferers), respectively.
Within the subgroup of sufferers with liver metastases at baseline, Tagrisso plus chemotherapy (43 sufferers) generated a median OS of 36.6 months in contrast with 28 months for Tagrisso alone (66 sufferers). The three-year OS charges have been 54% and 35%, respectively. In sufferers with out liver metastases at baseline, the median OS was 49.6 months for Tagrisso plus chemotherapy (236 sufferers) versus 41.8 months for Tagrisso alone (212 sufferers).
For sufferers with bone metastases, the median OS was 40.2 months for Tagrisso plus chemotherapy (132 sufferers) versus 32.3 months for Tagrisso monotherapy (142 sufferers). The three-year OS charges have been 55% and 42%, respectively. In sufferers with out bone metastases, the median OS was not reached and 44.5 months for Tagrisso plus chemotherapy (147 sufferers) and Tagrisso alone (136 sufferers), respectively.
Lastly, in sufferers harboring TP53 alterations, these given Tagrisso plus chemotherapy (46 sufferers) skilled a median OS of 51.1 months versus 43.1 months for these administered Tagrisso alone (40 sufferers). The three-year OS charges have been 65% and 58%, respectively. In sufferers with TP53 wild-type illness, the median OS was not reached for Tagrisso plus chemotherapy (33 sufferers) and never reached for Tagrisso alone (34 sufferers).
How Was the FLAURA2 Trial Designed?
Notably, prior knowledge from this examine supported the February 2024 FDA approval of Tagrisso plus platinum-based chemotherapy to be used in sufferers with domestically superior or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved check.
FLAURA2 enrolled sufferers a minimum of 18 years of age with beforehand untreated, pathologically confirmed domestically superior or metastatic nonsquamous NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations. Sufferers have been additionally required to have a World Well being Group efficiency standing of 0 or 1. Sufferers with secure CNS metastases have been allowed to enroll, and mind scans have been necessary at baseline.
Sufferers have been randomly assigned to obtain Tagrisso at 80 mg per day together with pemetrexed at 500 mg/m2 and carboplatin at space below the curve 5 or cisplatin at 75 mg/m2 as soon as each three weeks for 4 cycles, adopted by Tagrisso at 80 mg as soon as per day plus pemetrexed at 500 mg/m2 as soon as each three weeks as upkeep remedy; or Tagrisso alone at 80 mg per day. Remedy past illness development was permitted at investigator discretion.
References
- “FLAURA2: exploratory general survival analyses in sufferers with poorer prognostic components handled with osimertinib ± platinum-pemetrexed as first-line remedy for EGFR-mutated superior NSCLC,” by Dr. Pasi A. Jänne, et al. Offered at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Summary LBA77.
- “Tagrisso plus chemotherapy demonstrated a median general survival of practically 4 years, the longest profit ever reported in a worldwide Section III trial in EGFR-mutated superior lung most cancers,” information launch; https://www.astrazeneca.com/media-centre/press-releases/2025/tagrisso-plus-chemotherapy-demonstrated-a-median-overall-survival-of-nearly-four-years.html
- “FDA approves osimertinib with chemotherapy with chemotherapy for EGFR-mutated non-small cell lung most cancers,” FDA; https://www.fda.gov/medicine/resources-information-approved-drugs/fda-approves-osimertinib-chemotherapy-egfr-mutated-non-small-cell-lung-cancer
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