Results from a phase III trial indicate that cetuximab should not be given alongside chemotherapy in patients with recurrent non-small-cell lung cancer (NSCLC) after platinum-based therapy.
In the open-label randomized trial, combination therapy with cetuximab and pemetrexed did not improve survival compared with pemetrexed alone, but was associated with significantly greater toxicity, including death.
“The identification of NSCLC patients most likely to benefit from cetuximab remains a challenge,” remark the study authors, Edward Kim (Levine Cancer Institute, Charlotte, North Carolina, USA) and colleagues, writing in The Lancet Oncology.
Cetuximab is a monoclonal antibody against the epidermal growth factor receptor (EGFR) and has been shown in preclinical and phase II studies to have activity against lung cancer. Given the great unmet need for new agents that are effective in patients who have become refractory to front-line chemotherapy, Kim’s team tested the efficacy of cetuximab in this setting.
A total of 939 patients with recurrent or progressive NSCLC after platinum-based therapy received either pemetrexed (500 mg/m²) or docetaxel (75 mg/m²) with or without cetuximab (400 mg/m² at first dose and 250 mg/m² weekly thereafter).
The study protocol was changed during follow-up due to a change in standard of care. The revised primary endpoint was progression-free survival (PFS) and only the 605 pemetrexed-treated patients were included in the primary analysis, 301 of whom also received cetuximab.
Median PFS was 2.9 months with cetuximab plus pemetrexed versus 2.8 months with pemetrexed, a nonsignificant difference with a hazard ratio of 1.03.
Serious adverse events were significantly more frequent with combination therapy than with pemetrexed alone; 41% and 29% of patients, respectively, experienced at least one such event.
The most common grade 3 or 4 adverse events with combination therapy were fatigue (11%), acneiform rash (11%), dyspnea (10%), and decreased neutrophil count (10%); and with pemetrexed alone were dyspnea (12%), decreased neutrophil count (9%), and fatigue (8%).
Furthermore, 3% of patients in the cetuximab and pemetrexed group died from adverse events as compared with 2% of patients given pemetrexed alone.
Finally, subgroup analysis failed to identify any patients in whom cetuximab plus pemetrexed was superior to pemetrexed alone, whether stratified by EGFR staining intensity or tumor histology.
The authors conclude: “Further work is needed to better define biomarkers that can identify patients who could most benefit from anti-EGFR antibody treatment in lung cancer.”
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