In the final analysis of the pivotal IPASS trial,1
overall survival, which was a secondary endpoint, was similar for
gefitinib and carboplatin/paclitaxel, reported Chih-Hsin
James Yang, MD, of National Taiwan University Hospital and
College of Medicine in Taipei, Taiwan.
"But the true effect of the initial randomized treatment on
overall survival is likely to have been confounded by subsequent
therapy-in particular, the switching of patients to the alternative
study treatment," Dr. Yang noted at the Presidential Symposium of
ESMO 2010. "Only 31% of the gefitinib group and 38% of the
chemotherapy group did not receive additional treatment," he
emphasized. In fact, about 40% received two more regimens
post-study.
The Iressa Pan-Asia Study (IPASS) included 1,217 Asian patients
with NSCLC, and the study population was clinically enriched for
sensitivity to anti-EGFR-tyrosine kinase therapy. The main analysis
demonstrated robust results for gefitinib in patients with mutated
EGFR2 and essentially changed clinical practice
for this subset of patients with NSCLC.
In the 2010 updated survival analysis of the intent-to-treat
population, median overall survival was 18.8 months with gefitinib
and 17.4 months with standard chemotherapy (HR = 0.90;
P = .109). Patients known to be EGFR mutation-positive also
demonstrated no overall survival differences according to
treatment, and no clinical or biomarker subgroup was predictive of
better overall survival with gefitinib, Dr. Yang reported. "This is
for the first time, a matured overall survival analysis is reported
in a large randomized phase III study comparing an first-line
EGFR-TKI with combination chemotherapy."
The study validated, however, that positive EGFR mutation status
is predictive of good outcomes with gefitinib over chemotherapy in
terms of PFS, response rate, and health-related quality of life, he
added. IPASS also demonstrated the importance of biomarker testing
in NSCLC, "making a significant step toward personalized
medicine."
EGFR Mutation Positivity a Good Sign
Jean-Charles Soria,
MD, of Gustave Roussy Institute in Villejuif, France,
suggested another reason for the similar survival outcomes in
IPASS, apart from subsequent post-study treatment. "EGFR mutation
positivity is not only a predictive marker [for good results with
gefitinib] but a prognostic marker as well," he said.
Dr. Soria pointed out that patients with an EGFR mutation seem
to have an intrinsically good prognosis compared to patients
without the mutation. Of additional benefit, their less aggressive
tumors allow such patients to undergo multiple lines of therapy, he
noted.
"It is not the sequence of therapy that counts but the fact that
such patients are exposed to an EGFR tyrosine kinase inhibitor in
general, and whether it is given first-line or later translates
into the same overall survival. There is no relevance in delaying
therapy if EGFR status is not available at the initial
consultation, especially in symptomatic patients," Dr. Soria
maintained. Nevertheless, he advocated using front-line gefitinib
(rather than chemo) on the basis of superior symptom improvement,
better quality of life, better PFS, and oral availability of the
drug. ■
References
1. Yang C-H, Fukuoka M, Mok TS, et al: Final overall survival
results from a phase III randomized, open-label, first-line study
of gefitinib V carboplatin/paclitaxel in clinically selected
patients with advanced non-small cell lung cancer in Asia. 35th
ESMO Congress. Abstract LBA2. Presented October 11,
2010.
2. Mok TS, Wu YL, Thongprasert S, et al: Gefitinib or
carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947-957, 2009.
