David Brill
Gefitinib is a viable second-line alternative to chemotherapy for advanced non-small-cell lung cancer, offering similar survival rates with fewer side effects, a large-scale international study has shown.
The drug represents “an important shift in the treatment paradigm for this disease,” the authors of the INTEREST* trial reported in The Lancet. [2008 Nov 22;372(9652):1809-18]
Patients who took oral gefitinib also had improved quality of life compared to those who received intravenous infusions of docetaxel.
Asian patients, women, non-smokers and patients with adenocarcinoma all had longer survival with gefitinib – echoing the findings of previous trials which have shown the drug to be of particular benefit in these subgroups. Unexpectedly, however, INTEREST also found similar survival patterns with docetaxel, suggesting that these may be generally-applicable prognostic factors unrelated to the specific treatment.
Gefitinib is not currently approved for routine use by the US FDA. However in some Asian countires it is authorized for second-line use. For example in Singapore patients are typically given a choice between second-line treatment options in the event that initial chemotherapy is unsuccessful.
“Should the patient go on to further chemotherapy or should they go on to other drugs like gefitinib? This study confirmed that gefitinib is just as good as chemotherapy but may have fewer side effects,” said Dr. Toh Chee Keong, a consultant medical oncologist at the National Cancer Centre Singapore (NCCS).
Given the choice, most patients prefer an oral drug to chemotherapy but the higher cost of gefitinib can sometimes be a prohibitive factor, he said.
It remains unclear exactly who will benefit most from each treatment and why, he added, but noted that in his experience a non-smoking status is the most powerful predictor of a positive response to gefitinib.
In contrast to previous trials, neither epidermal growth factor receptor (EGFR) gene copy-number nor EGFR protein expression predicted survival with gefitinib in INTEREST.
The study is one of the few phase III clinical trials to directly compare the efficacy of docetaxel with an EGFR tyrosine kinase inhibitor. The analysis included 1,433 patients who had not responded to previous chemotherapy, recruited from 149 centers in 24 countries between March 1 2004 and February 17 2006.
The most frequent side effects of gefitinib were acne, rash and diarrhea. Just 4 percent of patients taking the drug experienced serious adverse events – a similar rate to that seen at NCCS, where Toh estimates that “less than 5 percent” of patients on gefitinib develop side effects to the point where they have to stop therapy.
For docetaxel the most common side effects in the trial were hematological toxic effects, hair loss and weakness. Serious adverse events occurred in 18 percent of patients in this group.
The non-inferiority of gefitinib was demonstrated by the median overall survival, which was 7.7 months in patients taking the drug compared to 8 months for those taking docetaxel. One-year survival rates were 32 and 34 percent in the respective groups.
Gefitinib patients were twice as likely to have a “sustained and clinically relevant improvement in quality of life,” as measured by the Functional Assessment of Cancer Therapy-Lung score (odds ratio 1.99; P<0.0001).>
The drug represents “an important shift in the treatment paradigm for this disease,” the authors of the INTEREST* trial reported in The Lancet. [2008 Nov 22;372(9652):1809-18]
Patients who took oral gefitinib also had improved quality of life compared to those who received intravenous infusions of docetaxel.
Asian patients, women, non-smokers and patients with adenocarcinoma all had longer survival with gefitinib – echoing the findings of previous trials which have shown the drug to be of particular benefit in these subgroups. Unexpectedly, however, INTEREST also found similar survival patterns with docetaxel, suggesting that these may be generally-applicable prognostic factors unrelated to the specific treatment.
Gefitinib is not currently approved for routine use by the US FDA. However in some Asian countires it is authorized for second-line use. For example in Singapore patients are typically given a choice between second-line treatment options in the event that initial chemotherapy is unsuccessful.
“Should the patient go on to further chemotherapy or should they go on to other drugs like gefitinib? This study confirmed that gefitinib is just as good as chemotherapy but may have fewer side effects,” said Dr. Toh Chee Keong, a consultant medical oncologist at the National Cancer Centre Singapore (NCCS).
Given the choice, most patients prefer an oral drug to chemotherapy but the higher cost of gefitinib can sometimes be a prohibitive factor, he said.
It remains unclear exactly who will benefit most from each treatment and why, he added, but noted that in his experience a non-smoking status is the most powerful predictor of a positive response to gefitinib.
In contrast to previous trials, neither epidermal growth factor receptor (EGFR) gene copy-number nor EGFR protein expression predicted survival with gefitinib in INTEREST.
The study is one of the few phase III clinical trials to directly compare the efficacy of docetaxel with an EGFR tyrosine kinase inhibitor. The analysis included 1,433 patients who had not responded to previous chemotherapy, recruited from 149 centers in 24 countries between March 1 2004 and February 17 2006.
The most frequent side effects of gefitinib were acne, rash and diarrhea. Just 4 percent of patients taking the drug experienced serious adverse events – a similar rate to that seen at NCCS, where Toh estimates that “less than 5 percent” of patients on gefitinib develop side effects to the point where they have to stop therapy.
For docetaxel the most common side effects in the trial were hematological toxic effects, hair loss and weakness. Serious adverse events occurred in 18 percent of patients in this group.
The non-inferiority of gefitinib was demonstrated by the median overall survival, which was 7.7 months in patients taking the drug compared to 8 months for those taking docetaxel. One-year survival rates were 32 and 34 percent in the respective groups.
Gefitinib patients were twice as likely to have a “sustained and clinically relevant improvement in quality of life,” as measured by the Functional Assessment of Cancer Therapy-Lung score (odds ratio 1.99; P<0.0001).>
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*Iressa NSCLC Trial Evaluating REsponse and Survival versus Taxotere
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