Cesare Gridelli1, Antonio Rossi2, Fortunato Ciardiello3, Filippo De Marinis4, Lucio Crinò5, Alessandro Morabito6, Floriana Morgillo3, Agnese Montanino6, Gennaro Daniele7, Maria Carmela Piccirillo7, Nicola Normanno8, Ciro Gallo9, Francesco Perrone7. 1. Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. Electronic address: cgridelli@libero.it. 2. Division of Medical Oncology, S.G. Moscati Hospital, Avellino, Italy. 3. Division of Medical Oncology and Hematology, Second University of Naples, Naples, Italy. 4. Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy. 5. Division of Medical Oncology, University of Perugia, Perugia, Italy. 6. Thoraco-Pulmonary Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- IRCCS, Naples, Italy. 7. Clinical Trials Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale"- IRCCS, Naples, Italy. 8. Cellular Biology and Biotherapy Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale, IRCCS, Naples, Italy. 9. Medical Statistics, Second University of Naples, Naples, Italy.
Abstract
BACKGROUND: About 20% of advanced non-small-cell lung cancer (NSCLC) cases harbor somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene. In these patients, the standard first-line treatments are the EGFR-tyrosine kinase inhibitors, such as gefitinib, erlotinib, or afatinib. Most of these patients develop resistance and relapse within about 1 year of initiation of an EGFR-tyrosine kinase inhibitor. Consequently, it is important to develop new combination strategies to delay this resistance. Preclinical data have showed that EGFR and vascular endothelial growth factor (VEGF) share a common downstream pathway, suggesting the important role of VEGF in the resistance to EGFR blockade. The combination of erlotinib and bevacizumab, an anti-VEGF agent, showed very interesting clinical results. PATIENTS AND METHODS: The bevacizumab plus erlotinib study (BEVERLY) is a randomized, open-label, phase III trial investigating first-line erlotinib plus bevacizumab versus erlotinib in patients with advanced NSCLC harboring activating EGFR mutations. The co-primary endpoints are investigator-assessed progression-free survival (PFS) and blinded, independent centrally reviewed PFS. The secondary endpoints include overall survival, quality of life, objective response rate, and safety. A total of 200 patients will be randomized 1:1 to receive oral erlotinib (150 mg daily) plus bevacizumab (15 mg/kg, intravenously, on day 1 of every 21-day cycle) or erlotinib alone, until objective disease progression or unacceptable toxicity or the patient's or physician's motivated decision to stop the treatment. CONCLUSION: If the primary endpoint of PFS is met, the erlotinib plus bevacizumab combination will be confirmed as the best first-line treatment for patients with advanced NSCLC harboring activating EGFR mutations.
RCT Entities:
BACKGROUND: About 20% of advanced non-small-cell lung cancer (NSCLC) cases harbor somatic mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene. In these patients, the standard first-line treatments are the EGFR-tyrosine kinase inhibitors, such as gefitinib, erlotinib, or afatinib. Most of these patients develop resistance and relapse within about 1 year of initiation of an EGFR-tyrosine kinase inhibitor. Consequently, it is important to develop new combination strategies to delay this resistance. Preclinical data have showed that EGFR and vascular endothelial growth factor (VEGF) share a common downstream pathway, suggesting the important role of VEGF in the resistance to EGFR blockade. The combination of erlotinib and bevacizumab, an anti-VEGF agent, showed very interesting clinical results. PATIENTS AND METHODS: The bevacizumab plus erlotinib study (BEVERLY) is a randomized, open-label, phase III trial investigating first-line erlotinib plus bevacizumab versus erlotinib in patients with advanced NSCLC harboring activating EGFR mutations. The co-primary endpoints are investigator-assessed progression-free survival (PFS) and blinded, independent centrally reviewed PFS. The secondary endpoints include overall survival, quality of life, objective response rate, and safety. A total of 200 patients will be randomized 1:1 to receive oral erlotinib (150 mg daily) plus bevacizumab (15 mg/kg, intravenously, on day 1 of every 21-day cycle) or erlotinib alone, until objective disease progression or unacceptable toxicity or the patient's or physician's motivated decision to stop the treatment. CONCLUSION: If the primary endpoint of PFS is met, the erlotinib plus bevacizumab combination will be confirmed as the best first-line treatment for patients with advanced NSCLC harboring activating EGFR mutations.
Authors: Alessia E Russo; Domenico Priolo; Giovanna Antonelli; Massimo Libra; James A McCubrey; Francesco Ferraù Journal: Lung Cancer (Auckl) Date: 2017-12-14