Iressa benefits Asians more than Caucasians
Longer survival, better objective response seen in ISEL study
KUALA LUMPUR
The exact reasons are not yet known, but Asians--especially women and those who never smoked--suffering from advanced nonsmall-cell lung cancer (NSCLC) and who have failed chemotherapy appear to get more benefits from treatment with gefitinib (Iressa) than their Caucasian counterparts.
They survive longer, more of them exprience tumor shrinkage, and they improve their quality of life, according to results of the Iressa Survival Evaluation in Lung cancer study (ISEL).
"Asian patients have a 97.7-percent chance of deriving benefit from Iressa treatment," said Dr. Gerardo Cornelio, oncologist at the University of the Philippines-Philippine General Hospital and Asian Hospital and Medical Center, citing results of the study.
Cornelio was one of several Asian specialists who attended an Asian media briefing organized by AstraZeneca in Kuala Lumpur in April, coinciding with the presentation of the ISEL study findings in the United States before the 96th annual meeting of the American Association for Cancer Research.
And for those who never smoked, the odds are even higher at 99.7 percent. The objective response rate among nonsmokers was also higher regardless of race--17.6 percent among Asians and 18.5 percent among non-Asians.
Cornelio noted that Asian patients enrolled in the international multicenter study (20 percent of the study population) survived on average four months longer than non-Asians, 9.5 months v. 5.5 months, a difference that was deemed statistically significant.
"[When we talk of advanced cancer] a few extra weeks or months can make a lot of difference," commented Dr. Mark Smith, senior medical director for oncology at AstraZeneca.
Nearly twice more Asian patients (12.4 percent) than non-Asians (6.8 percent) also experienced tumor shrinkage (objective response rate).
The survival rate among Asians was also much better than the overall median survival rate of the ISEL study, which was 5.6 months.
Their quality of life also improved with significant symptom relief.
Better than the overall
ISEL involved 1,692 patients from 28 countries, 342 of them Asians, including 57 Filipinos. The other Asian patients came from Malaysia, Singapore, Taiwan, and Thailand.
Overall, the difference in results between the Iressa-treated patients and those given placebo and best supportive care were not statistically significant. The one-year survival rate was 27 percent with Iressa and 21 percent with placebo while the median survival rate was 5.6 months versus 5.1 months.
But the difference mattered when a planned subgroup analysis of Asian patients was made.
The results validated earlier findings that Asians tended to res-pond better to Iressa, a target-specific drug that stops the epidermal growth factor (EGF) from binding to its receptor on the cell surface, an action that prevents cancer cells from proliferating. The binding of EGF to its receptor activates the enzyme tyrosine kinase, which signals cells to multiply. In effect, Iressa shuts off the cancer-cell mutation.
It is thought that this mode of action may help explain the difference in treatment response between Asians and Caucasians, between men and women, and between those with a type of cancer called adenocarcinoma and other types.
Prof. Tony Mok of the Chinese University of Hong Kong noted that in previous studies, the frequency EGFR mutation was noted to be higher among Japanese (26 percent) than Americans (eight percent), among women (18 percent) than men (seven percent), and among those with adenocarcinoma (15 percent) than other type of cancer (two percent).
Early indications
Mok said the first indication that Asians were more sensitive to Iressa was seen in a 2003 study in which the tumor-response rate was 27.5 percent among Japanese as against 10.4 percent among non-Japanese, while the time-to-disease progression was twice longer among Japanese (3.8 months) than non-Japanese (1.9 months).
Succeeding phase-II studies in China, Taiwan, and Korea yielded similar findings. In these studies, Iressa attained tumor response in 26 to 38 percent of Asian patients with advanced NSCLC, higher than the rates attained among Caucasians.
Mok said these were bolstered by a multinational collaborative study between Europe and Asia that showed partial response rates of 46.9 percent among Asians compared with 19.4 percent among Caucasians.
With these findings, Mok said future Iressa research will focus on its potential use as first-line therapy for Asian patients with adenocarcinoma of the lungs and as a postoperative adjuvant therapy, as well as on using EGFR mutation as basis for selecting patients who may be given Iressa.
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