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Results of a phase III multicenter, open-label study demonstrated that first-line treatment with a combination of cetuximab and a taxane/carboplatin (TC) significantly approved the overall response rate (ORR) and led to slight improvement in overall survival (OS). The study did not meet its primary endpoint of progression-free survival (PFS) as assessed by an independent radiologic review committee (IRCC).
The study enrolled 676 patients with stage III/IVB non–small cell lung cancer (NSCLC) who had not been treated previously with chemotherapy or an EGFR-inhibiting agent. The study was not limited by histology, KRAS mutation, or EGFR expression.
All 645 patients included in this analysis received up to 6 cycles of TC, comprising paclitaxel or docetaxel plus carboplatin. Approximately half were randomized to therapy with cetuximab until progression or intolerable toxicity. Patients continued on cetuximab even after completing chemotherapy. Overall, 80% of patients completed 80% of the planned therapy.
PFS by IRRC was 4.40 months in the TC/cetuximab cohort compared with 4.24 months for the TC-only cohort, which was not significant. The investigators found that OS trended toward TC/cetuximab, but the advantage was not significant (9.69 mo vs 8.38 mo, respectively; P = .1685).
TC/cetuximab significantly outperformed TC alone in ORR according to IRRC. This was 25.75% in the TC/cetuximab arm compared with 17.2% in the TConly arm (P = .0066).
Cetuximab-associated infusion reactions and skin toxiciti
es were the only significant adverse events observed. Approximately 59% (n = 185) developed acneiform rash. Investigators noted that the 55 patients receiving cetuximab that developed acneiform rash early on had longer OS than the 130 patients who did not (10.4 mo vs 8.9 mo, respectively). Acneiform rash led to 5 discontinuations in this group.
A total of 63% of patients taking cetuximab and 56% of patients receiving only chemotherapy developed grade 3-4 neutropenia; both arms had a 4% rate of febrile neutropenia. Two drug-related deaths occurred in the TC-only cohort and none in the cetuximab group.
The authors concluded that cetuximab demonstrated activity when administered with a platinum-based regimen compared with tyrosine kinase inhibitors of EGFR, which do not demonstrate activity when added to chemotherapy. They said, “Identification of biomarkers to predict patient response to therapy remains a critical issue for cetuximab in NSCLC.”
Lynch TJ, Patel T, Dreisbach L, et al. Cetuximab and first-line taxane/carboplatin chemotherapy in advanced non–small cell lung cancer: Results of the randomized multicenter phase III trial BMS099. J Clin Oncol. 2010;28(6):911-917.