S S Ramalingam1, A Kotsakis2, A A Tarhini3, D E Heron4, R Smith3, D Friedland5, D P Petro5, L E Raez6, J R Brahmer7, J S Greenberger4, S Dacic8, P Hershberger9, R J Landreneau10, J D Luketich10, C P Belani11, A Argiris12. 1. Department of Hematology/Oncology, Winship Cancer Institute of Emory University School of Medicine, Atlanta, USA. 2. Department of Medical Oncology, University Hospital of Heraklion, Crete, Greece. 3. Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA. 4. Department of Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA. 5. Department of Medicine, Division of Medical Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA. 6. Department of Medical Oncology, Memorial Cancer Institute, Pembroke Pines, USA. 7. The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, USA. 8. Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, USA. 9. Department of Pharmacology and Chemical Biology, University of Pittsburgh Medical Center, Pittsburgh, USA. 10. Department of Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, USA. 11. Department of Medicine, Division of Hematology/Oncology, Penn State Hershey Cancer Institute, Hershey, USA. 12. Department of Medicine, Division of Hematology/Oncology, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, USA. Electronic address: argiris@uthscsa.edu.
Abstract
BACKGROUND: Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). METHODS: Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). RESULTS: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. CONCLUSIONS: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.
BACKGROUND:Cetuximab has demonstrated improved efficacy in combination with chemotherapy and radiotherapy. We evaluated the integration of cetuximab in the combined modality treatment of stage III non-small cell lung cancer (NSCLC). METHODS:Patients with surgically unresectable stage IIIA or IIIB NSCLC were treated with chest radiotherapy, 73.5 Gy (with lung and tissue heterogeneity corrections) in 35 fractions/7 weeks, once daily (63 Gy without heterogeneity corrections). Cetuximab was given weekly during radiotherapy and continued during consolidation therapy with carboplatin and paclitaxel up to a maximum of 26 weekly doses. The primary endpoint was overall survival. Baseline tumor tissue was analyzed for EGFR by fluorescence in situ hybridization (FISH). RESULTS: Forty patients were enrolled in this phase II study. The median overall survival was 19.4 months and the median progression-free survival 9.3 months. The best overall response rate in 31 evaluable patients was 67%. No grade 3 or 4 esophagitis was observed. Three patients experienced grade 3 rash; 16 patients (69%) developed grade 3/4 neutropenia during consolidation therapy. One patient died of pneumonitis, possibly related to cetuximab. EGFR gene copy number on baseline tumor tissues, analyzed by FISH, was not predictive of efficacy outcomes. CONCLUSIONS: The addition of cetuximab to chest radiotherapy and consolidation chemotherapy was tolerated well and had modest efficacy in stage III NSCLC. Taken together with the lower incidence of esophagitis, our results support evaluation of targeted agents instead of chemotherapy with concurrent radiotherapy in this setting.