ASCO 2009: EGFR Mutation Predicts Response to Gefitinib in Patients with NSCLC

Roxanne Nelson

May 19, 2009

May 19, 2009 — Nonsmall-cell lung cancer (NSCLC) patients with a mutation in the epidermal growth-factor receptor (EGFR) gene appear to be more likely to benefit from gefitinib (Iressa) than from conventional chemotherapy.

The full results will be presented at the upcoming 2009 Annual Meeting of the American Society of Clinical Oncologists (ASCO), and were previewed in a presscast on May 14.

Among patients with EGFR mutations, median progression-free survival was 9.5 months with gefitinib and 6.3 months with carboplatin/paclitaxel, lead author Masahiro Fukuoka, MD, PhD, professor of medicine at Kinki University School of Medicine in Osaka, Japan, told journalists. Patients without EGFR mutations experienced a median progression-free survival of 5.5 months with carboplatin/paclitaxel and 1.5 months with gefitinib.

The biomarker data were drawn from the IPASS (IRESSA Pan-Asia Study) study, a randomized trial conducted to evaluate the efficacy, safety, and tolerability of gefitinib vs carboplatin/paclitaxel as first-line treatment in a clinically selected population of Asian patients. The trial enrolled 1217 patients from 9 Asian countries who were chemotherapy-naïve, light or never smokers, and had who been diagnosed with stage IIIB/IV adenocarcinoma NSCLC.

The primary end point of this segment of the study was progression-free survival (Cox proportional hazards), and the secondary end point was objective response rate (logistic regression) by biomarker status. Of the 1217 patients in the cohort, 683 provided tissue samples, and EGFR mutation status was evaluable in 437.

Previous results from the IPASS study demonstrated that first-line treatment with gefitinib was more effective for slowing tumor growth than conventional chemotherapy in this population.

"The study exceeded our primary objective and demonstrated the superiority of gefitinib," said Dr. Fukuoka. "The hazard ratio was 0.74, but it was not consistent over time."

He pointed out that the first 6 months of progression-free survival favored carboplatin/paclitaxel, whereas the second 6 months favored gefitinib.

Overall Progression-Free Survival Among IPASS Participants

Progression-Free Survival Gefitinib,
n = 609
n = 608
Events 453 (74.4%) 497 (81.7%)
Median progression-free survival 5.7 months 5.8 months
4 months progression-free 61% 74%
6 months progression-free 48% 48%
12 months progression-free 25% 7%


For the biomarker analysis, the researchers observed that mutations in the EGFR gene were a strong predictive factor for the efficacy of gefitinib, compared with carboplatin/paclitaxel.

Of the tissue samples attained, 60% were positive for mutations, explained Dr. Fukuoka. "The results of progression-free survival by mutation status were striking," he said. "And treatment results were constant over time."

Progression-Free Survival by Mutation Status

  EGFR Mutation Positive EGFR Mutation Negative
Gefitinib, n 132 91
Carboplatin/paclitaxel, n 129 85
Gefitinib, n (%) 97 (73.5) 88 (96.7)
Carboplatin/paclitaxel, n (%) 111 (86.0) 70 (82.4)
Median progression-free survival    
Gefitinib 9.5 months 1.5 months
Carboplatin/paclitaxel 6.3 months 5.5 months


EGFR mutation status was a strong predictive biomarker in this clinically selected first-line setting, concluded Dr. Fukuoka, "indicating that a molecularly defined population will benefit most from first-line gefitinib."

He also added that the data for overall survival are not yet completed and that it is too soon to know how it is affected by EGFR mutation status.

Commenting on the study, Richard L. Schilsky, MD, president of ASCO and professor of medicine at the University of Chicago in Illinois, pointed out these results add strength to previous findings. "The important thing about this study is that it really affirms, in a large randomized trial, much of what we've been seeing coming out in smaller studies over the past several years," he said.

"We now need to think about nonsmall cell lung cancer as at least 2 distinct types of cancer," he added. Patients with an increase in the number of EGFR mutations might be best treated with agents like gefitinib, whereas standard chemotherapy might be the best first-line treatment for those without mutations.

One or more of the authors has had an advisory role/consultant, employment, and/or stock ownership with AstraZeneca; and has received research funding/honoraria from AstraZeneca, Takeda, sanofi-aventis, Taiho, Chugai, Roche, Eli Lilly, Pfizer, and/or Merck. Dr. Schilsky has no relevant financial relationships to disclose since taking office in June 2007, but continues to serve (with compensation) on a Data Monitoring Committee for Novartis Oncology.

2009 Annual Meeting of the American Society of Clinical Oncologists (ASCO): Abstract 8006. To be presented May 31, 2009.