Among 31 patients who took Iressa during the trial, 55 percent had their tumors shrink noticeably in a CAT scan, and all but two had tumors that either shrank or did not grow for at least a month. The median rate of time that patients survived without their cancer progressing was about nine months. Sequist says that chemotherapy typically has response rates of 20 to 30 percent, with a survival advantage of about four months. “We had quite an improvement over what we typically see when we give a general one-size-fits-all treatment,” she says. Because Iressa is an oral pill taken daily, the patients avoided the toxic side effects of daily intravenous chemotherapy treatments. The two patients who experienced a worsening of their disease were later found to have a type of EGFR mutation that confers resistance to the drug; the distinction between EGFR mutations had not been discovered when the trial began.
Iressa’s maker, AstraZeneca, stopped marketing the drug in the United States after this study began, because of its poor showing in clinical trials. However, a similar drug, Tarceva, is available and is thought to have similar effects in patients.
In an accompanying editorial, Frances Shepherd, a lung-cancer researcher at Princess Margaret Hospital, in Toronto, said that while the study showed that screening tumors for their molecular makeup before treatment is feasible, it does not yet provide solid evidence that EGFR inhibitors should be used before chemotherapy. Shepherd points to previous studies showing that people with EGFR mutations survive longer under standard chemotherapy than patients without these mutations, suggesting that they might fare better regardless of their therapy. To know whether the drug is truly better than chemotherapy would require a randomized trial of the two therapies in this patient population. An ongoing study in Spain is currently addressing this question.
Pao says that while the study doesn’t provide definitive answers about how to use EGFR inhibitors, it represents an important step toward personalized cancer treatment. The study, he says, is one of the first attempts to genetically screen cancer patients before treatment as a way to guide clinical decision making, rather than identifying susceptible patient populations after the fact.