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Bending the Curve Trial by Trial
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FLAURA

Osimertinib versus gefitinib or erlotinib in previously untreated EGFR mutation-positive advanced NSCLC (FLAURA)

Phase 3N = 556NCT02296125

Population
Previously untreated EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC
Design
Double-blind phase 3 trial, 1:1 randomisation; primary endpoint investigator-assessed progression-free survival; overall survival a secondary endpoint (final analysis published separately)
Primary endpoint
PFS
Arms
  • Osimertinib (experimental, n = 279): Osimertinib 80 mg once daily
  • Gefitinib or erlotinib (control, n = 277): Gefitinib 250 mg or erlotinib 150 mg once daily, analysed as one comparator group
People
Soria JC, FLAURA Investigators
PFSHR 0.46 (95% CI 0.37–0.57)Δ median PFS+8.7 monthsΔ ORR+4 pointsΔ median DOR+8.7 monthsOSHR 0.63 (95% CI 0.45–0.88)Δ 18-month OS+12 points
Show the numbers
Results reported for FLAURA
EndpointAnalysisOsimertinibGefitinib or erlotinibEffect
PFSAll randomised patients (n=556)Investigator-assessedprimarySoria 2018median 18.9 monthsmedian 10.2 monthsHR 0.46 (95% CI 0.37–0.57)P<0.001
ORRAll randomised patients (n=556)primarySoria 201880%76%P=0.24Odds ratio 1.27 (95% CI 0.85 to 1.90).
DORAll randomised patients (n=556)primarySoria 2018median 17.2 months (13.8–22.0)median 8.5 months (7.3–9.8)—
OSAll randomised patients (n=556)interimSoria 201883% at 18 mo (78–87%)71% at 18 mo (65–76%)HR 0.63 (95% CI 0.45–0.88)P=0.007Overall survival data were immature (25% maturity); the abstract labels the P value nonsignificant in the interim analysis.
OSAll randomised patients (n=556)finalRamalingam 2020median 38.6 months (34.5–41.8)median 31.8 months (26.6–36.0)HR 0.8P=0.046Hazard ratio for death 0.80 with a 95.05% confidence interval of 0.64 to 1.00 (as published; not a 95% interval).
Results reported for FLAURA
EndpointAnalysisOsimertinibGefitinib or erlotinibEffect
PFSAll randomised patients (n=556)Investigator-assessedprimarySoria 2018median 18.9 monthsmedian 10.2 monthsHR 0.46 (95% CI 0.37–0.57)P<0.001
ORRAll randomised patients (n=556)primarySoria 201880%76%P=0.24Odds ratio 1.27 (95% CI 0.85 to 1.90).
DORAll randomised patients (n=556)primarySoria 2018median 17.2 months (13.8–22.0)median 8.5 months (7.3–9.8)—
OSAll randomised patients (n=556)interimSoria 201883% at 18 mo (78–87%)71% at 18 mo (65–76%)HR 0.63 (95% CI 0.45–0.88)P=0.007Overall survival data were immature (25% maturity); the abstract labels the P value nonsignificant in the interim analysis.
OSAll randomised patients (n=556)finalRamalingam 2020median 38.6 months (34.5–41.8)median 31.8 months (26.6–36.0)HR 0.8P=0.046Hazard ratio for death 0.80 with a 95.05% confidence interval of 0.64 to 1.00 (as published; not a 95% interval).
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.460.37–0.57
OS0.630.45–0.88
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%010203040Months (modelled)
  • Osimertinib (experimental)
  • Gefitinib or erlotinib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsOsimertinibGefitinib or erlotinib
0100.0%100.0%
1264.4%44.2%
2441.5%19.6%
3527.7%9.3%
4717.8%4.1%
Illustrative — modelled from reported values, not trial data. DOR, primary.
0%25%50%75%100%010203040Months (modelled)
  • Osimertinib (experimental)
  • Gefitinib or erlotinib (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsOsimertinibGefitinib or erlotinib
0100.0%100.0%
1164.2%40.8%
2241.2%16.6%
3227.5%7.4%
4317.7%3.0%
Primary publication: Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125. PubMedDOI

Appears in

Sources

  1. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018;378(2):113-125.

    PubMedDOI

  2. Ramalingam SS, Vansteenkiste J, Planchard D, Cho BC, Gray JE, Ohe Y, et al. Overall Survival with Osimertinib in Untreated, EGFR-Mutated Advanced NSCLC. N Engl J Med. 2020;382(1):41-50.

    PubMedDOI