A multicenter phase II study of sorafenib monotherapy in clinically selected patients with advanced lung adenocarcinoma after failure of EGFR-TKI therapy (Chinese Thoracic Oncology Group,CTONG 0805) |
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Authors: | Qing Zhou Cai-cun Zhou Gong-yan Chen Ying Cheng Cheng Huang Li Zhang Chong-rui Xu Ai-wu Li Hong-hong Yan Jian Su Xu-chao Zhang Jin-ji Yang Yi-long Wu |
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Institution: | 1. Guangdong Lung Cancer Institute, Guangdong General Hospital & Guangdong Academy of Medical Sciences, Guangzhou 510080, China;2. Shanghai Pulmonary Hospital, Shanghai, China;3. Haerbin Medical University Affiliated Tumor Hospital, Haerbin, China;4. Jilin Province Tumor Hospital, Jiling, China;5. Fujian Province Tumor Hospital, Fuzhou, China;6. Sun Yat-Sen University Cancer Center, Guangzhou, China |
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Abstract: | ObjectivesAim of the study was to investigate efficacy and safety of sorafenib in patients with advanced lung adenocarcinoma after failure of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) therapy.Patients and methodsPatients who were diagnosed with stage IIIB or stage IV lung adenocarcinoma, and benefited from one prior EGFR-TKI therapy and then failed, were eligible. No more than one previous chemotherapy regimen was permitted. Patients received oral sorafenib 400 mg twice daily continuously until disease progression or intolerable toxicity. Primary endpoint was disease control rate (DCR). Secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). For patients who agreed to provide peripheral blood or tumor tissue, we analyzed the genotype of Bcl-2-interacting mediator of cell death (BIM) deletion polymorphism and EGFR mutation status.ResultsOf 65 enrolled patients, 64 were evaluable. The DCR was 32.8%, which did not meet the predefined statistical hypothesis of 38.4%. The median PFS and OS were 3.7 months 95% (confidence interval), 3.5–3.9 months] and 7.4 months (95% CI, 5.7–9.2 months), respectively. Logistic regression analysis showed no correlation between DCR and age, gender, smoking status and performance status. Hand-foot syndrome (HFS) was the predominant toxicity occurring in 71.9% of patients. Fourteen patients (21.9%) had ≥grade 2 dermatologic reactions that resulted sorafenib dose reduction in three patients (4.7%). Of 36 patients, the BIM deletion polymorphism was found in 3, and no response to sorafenib was observed. In 30 tumor tissues, 22 EGFR active mutations were found. The DCR had no significant difference between mutation-positive and wild-type patients (31.8% vs. 42.9%, respectively; HR, 0.622; p = 0.665).ConclusionSorafenib monotherapy did not achieve positive result in patients defined in our trial and we need better biomarker to determine the population who can benefit from sorafenib treatment (ClinicalTrials.gov number: NCT00922584). |
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Keywords: | Sorafenib Carcinoma Non-small cell lung cancer Phase II clinical trial EGFR-TKI Resistance |
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