David E Gerber1, Paul Swanson2, Ariel Lopez-Chavez3, Lucas Wong4, Afshin Dowlati5, Nathan A Pennell6, Damien M Cronier7, Amy Qin8, Robert Ilaria9, Jan Cosaert10, Ashwin Shahir11, Maria Q Baggstrom12. 1. The University of Texas, Southwestern Medical Center at Dallas, Harry Hines Blvd., Mail Code 8852, Dallas, TX 75390-8852, USA. Electronic address: david.gerber@utsouthwestern.edu. 2. Hematology/Oncology Associates of the Treasure Coast, Port Saint Lucie, FL 34952, USA. Electronic address: paulmswanson@msn.com. 3. Oregon Health and Science University, Portland, OR 97239, USA. Electronic address: lopezcha@ohsu.edu. 4. Scott & White Clinic, Hematology-Oncology, Temple, TX 76508, USA. Electronic address: lwong@sw.org. 5. Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: afshin.dowlati@case.edu. 6. Cleveland Clinic, Cleveland, OH 44195, USA. Electronic address: penneln@ccf.org. 7. Eli Lilly and Company, Windlesham GU20 6PH, UK. Electronic address: cronier_damien@lilly.com. 8. Eli Lilly and Company, Bridgewater, NJ 08807, USA. Electronic address: amy.qin@lilly.com. 9. Eli Lilly and Company, Indianapolis, IN 46285, USA. Electronic address: Ilaria_robert_l@lilly.com. 10. Sotio a.s., 170 00 Prague 7, Czech Republic. Electronic address: jan.cosaert2@gmail.com. 11. Eli Lilly and Company, United Kingdom of Great Britain and Northern Ireland, UK. 12. Washington University, St. Louis, MO 63130, USA. Electronic address: mbaggstr@dom.wustl.edu.
Abstract
BACKGROUND: In non-small cell lung cancer (NSCLC), platelet-derived growth factor receptor (PDGFR) mediates angiogenesis, tissue invasion, and tumor interstitial pressure. Olaratumab (IMC-3G3) is a fully human anti-PDGFRα monoclonal antibody. This Phase II study assessed safety and efficacy of olaratumab+paclitaxel/carboplatin (P/C) versus P/C alone for previously untreated advanced NSCLC. MATERIALS AND METHODS: Patients received up to six 21-day cycles of P 200mg/m2 and C AUC 6 (day 1)±olaratumab 15mg/kg (days 1 and 8). Primary endpoint was PFS. Olaratumab was continued in the olaratumab+P/C arm until disease progression. RESULTS:131 patients were: 67 with olaratumab+P/C and 64 with P/C; 74% had nonsquamous NSCLC. Median PFS was similar between olaratumab+P/C and P/C (4.4 months each) (HR 1.29; 95% CI [0.86-1.93]; p=0.21). Median OS was similar between olaratumab+P/C (11.8 months) and P/C (11.5 months) (HR 1.04; 95% CI [0.68-1.57]; p=0.87). Both arms had similar toxicity profiles. All evaluable cases were PDGFR-negative by immunohistochemistry. Tumor stroma PDGFR expression was evaluable in 23/131 patients, of which 78% were positive. CONCLUSIONS: The addition of olaratumab to P/C did not result in significant prolongation of PFS or OS in advanced NSCLC. Olaratumab studies in other patient populations, including soft tissue sarcoma (NCT02783599), pancreatic cancer (NCT03086369), and pediatric malignancies (NCT02677116) are underway.
RCT Entities:
BACKGROUND: In non-small cell lung cancer (NSCLC), platelet-derived growth factor receptor (PDGFR) mediates angiogenesis, tissue invasion, and tumor interstitial pressure. Olaratumab (IMC-3G3) is a fully human anti-PDGFRα monoclonal antibody. This Phase II study assessed safety and efficacy of olaratumab+paclitaxel/carboplatin (P/C) versus P/C alone for previously untreated advanced NSCLC. MATERIALS AND METHODS:Patients received up to six 21-day cycles of P 200mg/m2 and C AUC 6 (day 1)±olaratumab 15mg/kg (days 1 and 8). Primary endpoint was PFS. Olaratumab was continued in the olaratumab+P/C arm until disease progression. RESULTS: 131 patients were: 67 with olaratumab+P/C and 64 with P/C; 74% had nonsquamous NSCLC. Median PFS was similar between olaratumab+P/C and P/C (4.4 months each) (HR 1.29; 95% CI [0.86-1.93]; p=0.21). Median OS was similar between olaratumab+P/C (11.8 months) and P/C (11.5 months) (HR 1.04; 95% CI [0.68-1.57]; p=0.87). Both arms had similar toxicity profiles. All evaluable cases were PDGFR-negative by immunohistochemistry. Tumor stromaPDGFR expression was evaluable in 23/131 patients, of which 78% were positive. CONCLUSIONS: The addition of olaratumab to P/C did not result in significant prolongation of PFS or OS in advanced NSCLC. Olaratumab studies in other patient populations, including soft tissue sarcoma (NCT02783599), pancreatic cancer (NCT03086369), and pediatric malignancies (NCT02677116) are underway.
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