Combination of Erlotinib and Pemetrexed to Treat Non–Small-Cell Lung Cancer

Chicago—A multicenter, open-label, randomized phase 2 study found that patients with nonsquamous, non–small-cell lung cancer (NSCLC) who took erlotinib and pemetrexed as a second-line treatment had significant improvements in overall survival and progression-free survival compared with a group that only received pemetrexed. The combination therapy of erlotinib and pemetrexed also had a tolerable safety profile. The results were presented at the ASCO meeting in a poster titled A Randomized Phase II Study of Pemetrexed versus Pemetrexed plus Erlotinib in Second-Line Treatment for Locally Advanced or Metastatic, Nonsquamous NSCLC. Between April 11, 2007, and July 27, 2010, the researchers enrolled 159 patients ≥18 years of age with stage IIIA, IIIB, or IV nonsquamous NSCLC at 24 study centers in 5 countries. Inclusion criteria included failure of a prior platinum-based chemotherapy regimen for advanced metastatic disease, eligibility for further chemotherapy following disease progression, and no previous exposure to agents directed at the human epidermal growth factor receptor, such as gefitinib, erlotinib, cetuximab, or trastuzumab. Patients were randomized in a 1:1 ratio to receive 500 mg/m2 of pemetrexed every 3 weeks or 500 mg/m2 of pemetrexed every 3 weeks plus 150 mg of erlotinib once daily. Patients in both arms received vitamin B12, folic acid supplementation, and prophylactic dexamethasone and received treatment until they had disease progression or intolerable toxicity. The US Food and Drug Administration has approved pemetrexed and erlotinib as second-line monotherapies to treat locally advanced or metastatic NSCLC. Baseline characteristics were similar between the groups. The median age was 61 years in the pemetrexed group and 64 years in the pemetrexed plus erlotinib group; there were 59% males in the pemetrexed group and 61% in the pemetrexed plus erlotinib group; and each group had approximately 99% Caucasians. The median progression-free survival was 3.19 months (95% confidence interval [CI], 1.94-3.38) in the pemetrexed plus erlotinib group compared with 2.89 months (95% CI, 2.88-4.70) in the pemetrexed group (hazard ratio [HR], 0.63; 95% CI, 0.40-0.90; P=.0047). The progression-free survival rates in the pemetrexed group were 42.4%, 22.7%, and 3.5% at 3, 6, and 12 months, respectively. The progression-free survival rates in the pemetrexed plus erlotinib group were 57.2%, 31.5%, and 18.8% at 3, 6, and 12 months, respectively. The median overall survival was 11.83 months (95% CI, 8.16-16.66) in the pemetrexed plus erlotinib group compared with 7.75 months (95% CI, 5.29-10.41) in the pemetrexed group (HR, 0.68; 95% CI, 0.47-0.98; P=.019). The differences in response rate (defined as complete response or partial response) and disease control rate (defined as the best response of complete response, partial response, or stable disease) were not statistically significant (P=.181 and P=.391, respectively). Patients who took pemetrexed plus erlotinib had more serious adverse events, treatment-emergent adverse events, and grade 3 or 4 toxicities compared with the pemetrexed-only group.