Abstract
Previous retrospective studies suggested that lung cancer patients with anaplastic lymphoma kinase (ALK) gene rearrangements are associated with sensitivity to pemetrexed chemotherapy. To determine the efficacy of pemetrexed based chemotherapy compared with non-pemetrexed based chemotherapy, we retrospectively evaluated clinical outcome in ALK positive non-small cell lung cancer (NSCLC) patients. We identified 126 patients with advanced, ALK-positive NSCLC who received 1st line cytotoxic chemotherapy from Seoul National University Hospital and Seoul National University Bundang Hospital. We compared response rate, progression-free survival, and overall survival according to chemotherapy regimens. We also analyzed the intra-cranial time to progression and proportion of ALK-positive cells as a predictive factor of pemetrexed efficacy. Forty eight patients received pemetrexed based chemotherapy and Seventy eight patients received non-pemetrexed based chemotherapy as first line systemic treatment. One hundred eighteen patients received platinum double combination chemotherapy. The pemetrexed based chemotherapy group shows superior overall response rate (44.7% versus 14.3%, p<0.001) and disease control rate (85.1% versus 62.3%, p=0.008). Pemetrexed based chemotherapy group had longer progression free survival (6.6 months versus 3.8 months, p<0.001). Exposure to pemetrexed and exposure to second generation ALK inhibitor were independent prognostic factors of overall survival (p=0.016 and p=0.011, respectively). Intra-cranial time to progression (TTP) was similar among treatment group (32.7 months versus 35.7 months, p= 0.733). Proportion of ALK positive cells was not statistically significant predictive factor of survival in pemetrexed based chemotherapy. Pemetrexed based regimen may prolong progression free survival compared with other regimens in ALK positive NSCLC in the first line setting. Exposure to pemetrexed is associated with improved survival compared with that of premetrexed-naive controls in ALK positive NSCLC.
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