Silvia Novello1, Giorgio Scagliotti2, Gilberto de Castro3, Murat Kiyik4, Rubén Kowalyszyn5, Karl-Matthias Deppermann6, Edurne Arriola7, Lionel Bosquee8, Ruslan D Novosiadly9, Tuan S Nguyen10, Amelie Forest9, Shande Tang11, Siva Rama Prasad Kambhampati12, Jan Cosaert13, Martin Reck14. 1. Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy. Electronic address: silvia.novello@unito.it. 2. Department of Oncology, University of Turin, San Luigi Hospital, Turin, Italy. 3. Clinical Oncology Service, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil. 4. Pulmonary Department, Yedikule Chest Disease Hospital, Istanbul, Turkey. 5. Clinical Research Center of Viedma Clinic, Rio Negro, Argentina. 6. Lung Center - Department of Pneumology, Sana Kliniken Düsseldorf, Düsseldorf, Germany. 7. Medical Oncology, Hospital del Mar, Barcelona, Spain. 8. Hospital Bois L-Abbaye, Seraing, Belgium. 9. Department of Cancer Immunobiology, Eli Lilly and Company, New York, New York. 10. Statistics-Oncology Department, Eli Lilly and Company, Indianapolis, Indiana. 11. Statistics-Oncology Department, Eli Lilly and Company, Bridgewater, New Jersey. 12. Global Pharmacokinetics/Pharmacodynamics and Pharmacometrics, Eli Lilly and Company, Bridgewater, New Jersey. 13. Clinical Sciences, Early Phase, Eli Lilly and Company, Bridgewater, New Jersey. 14. Department of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
Abstract
INTRODUCTION: Type 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting. METHODS: In this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) toreceive 20 mg/kg cixutumumab, 500 mg/m2 pemetrexed, and 75 mg/m2 cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed. RESULTS: The mean age of the intent-to-treat population (n = 172) was 59 years (range 32-83). Median progression-free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81-1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64-1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred. CONCLUSIONS:Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.
RCT Entities:
INTRODUCTION: Type 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting. METHODS: In this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m2 pemetrexed, and 75 mg/m2 cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed. RESULTS: The mean age of the intent-to-treat population (n = 172) was 59 years (range 32-83). Median progression-free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81-1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64-1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred. CONCLUSIONS: Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported.
Authors: A Argiris; J W Lee; J Stevenson; M G Sulecki; V Hugec; N W Choong; J N Saltzman; W Song; R M Hansen; T L Evans; S S Ramalingam; J H Schiller Journal: Ann Oncol Date: 2017-12-01 Impact factor: 32.976
Authors: Tufia C Haddad; Jun He; Ciara C O'Sullivan; Beiyun Chen; Donald Northfelt; Amylou C Dueck; Karla V Ballman; Kathleen S Tenner; Hannah Linden; Joseph A Sparano; Judith O Hopkins; Chamath De Silva; Edith A Perez; Paul Haluska; Matthew P Goetz Journal: Breast Cancer Res Treat Date: 2021-04-14 Impact factor: 4.872