Skip to content
Bending the Curve Trial by Trial
?

ISEL

Iressa vs Best Supportive Care - 2nd/3rd Line Survival Study

Phase 3N = 1,692NCT00242801

Population
Locally advanced or metastatic NSCLC, refractory to or intolerant of the latest chemotherapy regimen (second or third line)
Design
Randomised (2:1), placebo-controlled, multicentre phase 3 study (Iressa Survival Evaluation in Lung Cancer) of gefitinib 250 mg/day plus best supportive care versus placebo plus best supportive care in patients with locally advanced or metastatic NSCLC refractory to or intolerant of their latest chemotherapy regimen. Coprimary endpoints survival in the overall population and in patients with adenocarcinoma; primary analysis by intention to treat per the abstract.
Primary endpoint
OS
Arms
  • Placebo plus best supportive care (control, n = 563): Placebo plus best supportive care
  • Gefitinib plus best supportive care (experimental, n = 1,129): Gefitinib 250 mg/day plus best supportive care
People
Thatcher N
OSHR 0.89 (95% CI 0.77–1.02)Δ median OS+0.5 monthsOSHR 0.84 (95% CI 0.68–1.03)Δ median OS+0.9 monthsOSHR 0.67 (95% CI 0.49–0.92)Δ median OS+2.8 months
Show the numbers
Results reported for ISEL
EndpointAnalysisGefitinib plus best supportive carePlacebo plus best supportive careEffect
OSOverall population (primary analysis by intention to treat per the abstract)primarymedian follow-up 7.2 monthsThatcher 2005median 5.6 monthsmedian 5.1 monthsHR 0.89 (95% CI 0.77–1.02)P=0.087Not a significant difference. The FDA 2015 summary review quotes p=0.11 for the same hazard ratio of 0.89; the Lancet abstract gives 0.087.
OSPatients with adenocarcinoma (n=812)primarymedian follow-up 7.2 monthsThatcher 2005median 6.3 monthsmedian 5.4 monthsHR 0.84 (95% CI 0.68–1.03)P=0.089Coprimary population; difference not significant.
OSNever-smokers (n=375); preplanned subgroupexploratorymedian follow-up 7.2 monthsThatcher 2005median 8.9 monthsmedian 6.1 monthsHR 0.67 (95% CI 0.49–0.92)P=0.012Preplanned subgroup analysis; not a coprimary population.
OSPatients of Asian origin (n=342); preplanned subgroupexploratorymedian follow-up 7.2 monthsThatcher 2005median 9.5 monthsmedian 5.5 monthsHR 0.66 (95% CI 0.48–0.91)P=0.01Preplanned subgroup analysis; not a coprimary population.
Results reported for ISEL
EndpointAnalysisGefitinib plus best supportive carePlacebo plus best supportive careEffect
OSOverall population (primary analysis by intention to treat per the abstract)primarymedian follow-up 7.2 monthsThatcher 2005median 5.6 monthsmedian 5.1 monthsHR 0.89 (95% CI 0.77–1.02)P=0.087Not a significant difference. The FDA 2015 summary review quotes p=0.11 for the same hazard ratio of 0.89; the Lancet abstract gives 0.087.
OSPatients with adenocarcinoma (n=812)primarymedian follow-up 7.2 monthsThatcher 2005median 6.3 monthsmedian 5.4 monthsHR 0.84 (95% CI 0.68–1.03)P=0.089Coprimary population; difference not significant.
OSNever-smokers (n=375); preplanned subgroupexploratorymedian follow-up 7.2 monthsThatcher 2005median 8.9 monthsmedian 6.1 monthsHR 0.67 (95% CI 0.49–0.92)P=0.012Preplanned subgroup analysis; not a coprimary population.
OSPatients of Asian origin (n=342); preplanned subgroupexploratorymedian follow-up 7.2 monthsThatcher 2005median 9.5 monthsmedian 5.5 monthsHR 0.66 (95% CI 0.48–0.91)P=0.01Preplanned subgroup analysis; not a coprimary population.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.890.77–1.02
OS0.840.68–1.03
OS0.670.49–0.92
OS0.660.48–0.91
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%02468101214Months (modelled)
  • Placebo plus best supportive care (control)
  • Gefitinib plus best supportive care (experimental)

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

Data table (modelled values)
MonthsPlacebo plus best supportive careGefitinib plus best supportive care
0100.0%100.0%
458.1%61.0%
738.6%42.0%
1122.4%25.6%
1414.9%17.7%
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%02468101214Months (modelled)
  • Placebo plus best supportive care (control)
  • Gefitinib plus best supportive care (experimental)

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

Data table (modelled values)
MonthsPlacebo plus best supportive careGefitinib plus best supportive care
0100.0%100.0%
459.8%64.4%
835.8%41.5%
1221.4%26.7%
1612.8%17.2%
Primary publication: Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366(9496):1527-37. PubMedDOI

Appears in

Sources

  1. Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet. 2005;366(9496):1527-37.

    PubMedDOI