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OPTIMAL: Erlotinib associated with threefold improvement in PFS for NSCLC
Zhou C. Lancet Oncol. 2011;doi:10.1016/S1470(11)70184-X.
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Results from a randomized phase 3 study conducted in China showed that PFS was 16 months for patients with non–small cell lung cancer assigned erlotinib compared with 4 months for those assigned to standard chemotherapy.
In an open-label, multicenter trial, 82 patients with stage IIIB or IV NSCLC and a confirmed activating mutation of epidermal growth factor receptor (exon 19 deletion or exon 21 L858R point mutation) were assigned to 150 mg daily oral erlotinib (Tarceva, OSI Pharmaceuticals) until disease progression or unacceptable toxic effects. Another 82 patients were assigned to up to four cycles of gemcitabine (Gemzar, Eli Lilly) plus carboplatin. Patients were stratified according to EGFR mutation type, histological subtype and smoking status.
Eighty-two patients in the erlotinib group and 72 in the chemotherapy group were included in this analysis.
Median PFS was 13.1 months in the erlotinib group vs. 4.6 months for chemotherapy (OR=0.16; 95% CI, 0.10-0.26).
Patients experienced fewer adverse events with erlotinib. Chemotherapy was associated with more grade-3/grade-4 neutropenia (42% vs. 0%) and thrombocytopenia (40% vs. 0%). Chemotherapy was also associated with increased treatment-related serious adverse events, including decreased platelet and neutrophil count.
The most common grade-3/grade-4 adverse events associated with erlotinib were increased alanine aminotransferase concentrations (4%) and skin rash (2%).
In an accompanying editorial, Tetsuya Mitsudomi, MD, of the Aichi Cancer Center Hospital in Nagoya, Japan, said these results demonstrate the value of EGFR mutation screening and patient selection when prescribing erlotinib. Although neither erlotinib nor gefitinib (Iressa, AstraZeneca) has been shown to improve OS, studies such as this highlight the important role tyrosine kinase inhibitors are likely to play.
“EGFR TKIs are undoubtedly key drugs for patients with EGFR mutations and should be used in early treatment,” Mitsudomi wrote. “However, when EGFR test results cannot be obtained in a reasonably short timeframe, first-line chemotherapy and second-line EGFR TKI after progression is a reasonable option if the patient is later shown to be EGFR mutation-positive.”
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The OPTIMAL study is one of several recently reported studies that evaluate the role of epidermal growth factor receptor (EGFR) tyrosine kinases (such as gefitinib or erlotinib) in patients with stage IIIB or IV non-small cell lung cancer whose tumors harbor EGFR mutations. This study showed that, in these molecularly selected patients, initial treatment with erlotinib leads to a longer progression-free survival than treatment with 4 cycles of gemcitabine and carboplatin (median PFS of 5 months vs 13 months, hazard ratio 0.16). As expected, patients randomized to erlotinib had significantly fewer toxicities from chemotherapy as well.Taken together with several other studies which were reported previously and since, this study demonstrates that patients whose tumors harbor EGFR mutations derive more benefit from initial treatment with an EGFR tyrosine kinase inhibitor such as erlotinib or gefitinib than conventional chemotherapy. Given the marked difference in outcomes for these patients, it is essential that we identify these patients with EGFR mutations using molecular testing of all patients with non-small cell lung cancer.
– Gregory J. Riely, MD, PhD
Medicial oncologist, Memorial Sloan-Kettering Cancer Center
Disclosure: Dr. Riely reports no financial disclosures.
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