MILAN – First-line erlotinib nearly tripled progression-free survival when compared with platinum-based chemotherapy in patients with advanced lung cancer carrying mutations activating the epidermal growth factor receptor.
Dr. Caicun Zhou
Median progression-free survival in the randomized, phase III OPTIMAL trial from China reached 13.1 months in patients given erlotinib (Tarceva), compared with 4.6 months in those given gemcitabine (Gemzar) plus carboplatin chemotherapy (hazard ratio 0.16, P less than .0001).
After a median follow-up of 15.6 months, 31 patients on erlotinib are still on the study, compared with only one on chemotherapy, lead author Dr. Caicun Zhou reported in a late-breaking abstract at the 35th Congress of the European Society for Medical Oncology. There was also much less toxicity with erlotinib.
OPTIMAL is the first phase III prospective study demonstrating that erlotinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is superior to standard platinum-based chemotherapy in Asian patients with EGFR mutation-positive non–small cell lung cancer (NSCLC).
Treatment with erlotinib more than doubled the objective response rate from 36% with chemotherapy to 83% (P less than .0001). The disease control rate also was superior at 96% vs. 82% (P = .002). Overall survival data were not available.
Subgroup analysis showed a consistent benefit with erlotinib regardless of histology, smoking history, age, sex, and disease stage, said Dr. Zhou, director of medical oncology at the Shanghai Pulmonary Hospital and of the Cancer Institute at Tongji University, Shanghai.
“A greater benefit was observed in patients with good performance status, indicating that Tarceva should be used as early as possible in this disease setting,” he told reporters at a press briefing.
Invited discussant Dr. Federico Cappuzzo said the 13-month progression-free survival is consistent with what has been observed in previous phase II erlotinib trials and seems better than results observed with gefitinib (Iressa), another EGFR inhibitor used first-line in this setting in some countries.
“Although these data could potentially suggest that erlotinib is superior to gefitinib, we don’t have a demonstration of that because we don’t have any trial directly comparing gefitinib with erlotinib and [that] therefore would allow us to conclude that one drug is superior to another,” he said.
At least four trials including the Iressa Pan-Asia Study (IPASS) have shown superior progression-free survival and response rates for gefitinib, compared with chemotherapy in Asian patients with EGFR-mutation–positive NSCLC. The problem for clinicians is the lack information on its efficacy, and that of erlotinib, in Caucasians, said Dr. Cappuzzo, director of medical oncology, Ospedale Civile-Livorno, Italy. EGFR mutations occur in about 40% of NSCLC patients from Asia, compared with about 10% of those in Western countries.
Two ongoing trials may address this knowledge gap: a single-arm study of gefitinib in Caucasians and the prospective phase III EURTAC trial evaluating the efficacy of erlotinib, compared with chemotherapy in patients in Spain, Italy, and France. The final results of EURTAC are expected next year, he said.
The first biomarker analysis from OPTIMAL also was presented at the meeting, and did not identify any additional markers (including c-MET amplification status) that predicted greater benefit with erlotinib. There was, however, a trend in the erlotinib arm for longer progression-free survival in patients with EGFR exon 19 deletions, compared with those with EGFR L858R mutations (15.3 months vs. 12.5 months, respectively, HR 0.58), reported Dr. Yi-long Wu from Guangdong General Hospital and Guangdong Academy of Medical Sciences in China.
“Exon 19 is probably the best predictor that we can use in our clinical practice,” Dr. Cappuzzo said.
OPTIMAL, also known as CTONG 0802, randomized 83 patients to receive erlotinib 150 mg per day until disease progression or unacceptable toxicity and 82 to receive gemcitabine/carboplatin administered in standard fashion for up to four cycles.
Erlotinib had less severe toxicity than chemotherapy (14 vs. 65 grade 3/4 events), except for skin rash, which was mostly mild or moderate in severity, Dr. Zhou reported.
Gefitinib is approved as first-line therapy in Europe and Asia for patients with EGFR-mutation-positive advanced NSCLC, but available only to selected patients in the United States under the Iressa Access Plan. Erlotinib is approved in the U.S. only as second- and third-line therapy for advanced NSCLC.
Roche Pharmaceutical Company China Ltd., sponsored the study. Dr. Zhou has received research grants and honoraria from F. Hoffman-La Roche Ltd., and Eli Lilly. Two co-investigators have received honoraria and served on the advisory boards of Roche and five other pharmaceutical companies.