Abstract 1475P
Background
Platelet-derived growth factor receptor alpha (PDGFRα) is overexpressed in pancreatic cancer (PC) and contributes to activation of pancreatic stellate cells and formation of characteristic desmoplastic stroma. Despite availability of treatments, PC has a poor prognosis, indicating an unmet need for novel therapies. This study evaluated the efficacy and safety of olaratumab (OLA), an anti-PDGFRα recombinant human immunoglobulin G subclass 1–type monoclonal antibody with standard first-line therapy gemcitabine and nab-paclitaxel in treatment-naïve patients (pts) with unresectable metastatic PC.
Methods
In this multicenter, randomized (1:1), double-blind, placebo-controlled study, pts with metastatic PC received gemcitabine (1000 mg/m2) and nab-paclitaxel (125 mg/m2) (GA) + OLA (20 mg/kg cycle 1 followed by 15 mg/kg) or placebo (PBO) on days 1, 8, and 15 in each 28-day cycle, until disease progression/intolerance. Primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), tumor response, and safety. Stratified log-rank, stratified Cox regression, and Kaplan-Meier estimation methods were used for statistical analysis of time-to-event outcomes.
Results
Overall, 159 pts were randomized to OLA+GA (n=81) or PBO+GA (n=78). Baseline disease characteristics were balanced between OLA+GA and PBO+GA arms, and the median age of the population was 66 years. No significant difference was observed for OS (9.1 vs 10.8 months; p=.79; HR: 1.05; 95% CI: 0.73–1.53) and PFS (5.6 vs 6.4 months; p=.38; HR: 1.19; 95% CI:0.81–1.76). Overall response rates and disease control rates were comparable for OLA+GA (30.5%, 69.5%) and PBO+GA (33.8%, 77.5%), respectively, and no significant difference was observed for duration of response (5.6 vs 5.6 months; p=.57; HR: 1.23; 95% CI: 0.61,2.47) between the arms. Treatment-emergent adverse events were comparable across treatment arms.
Conclusions
Olaratumab combined with chemotherapy failed to improve OS or PFS for pts with unresectable metastatic PC; safety was manageable.
Clinical trial identification
NCT03086369 (22nd March 2017).
Editorial acknowledgement
Editorial assistance was provided by Angela Lorio from Syneos Health, North Carolina, USA.
Legal entity responsible for the study
Eli Lilly & Company.
Funding
Eli Lilly & Company.
Disclosure
F. Gardner: Non-Financial Interests, Institutional, Invited Speaker: Epizyme; Non-Financial Interests, Institutional, Invited Speaker: Regeneron/Sanofi; Non-Financial Interests, Institutional, Invited Speaker: Pfizer. Z. Wainberg: Non-Financial Interests, Institutional, Invited Speaker: Amgen; Non-Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Institutional, Invited Speaker: Daiichi; Non-Financial Interests, Institutional, Invited Speaker: Bayer; Non-Financial Interests, Institutional, Invited Speaker: BMS; Non-Financial Interests, Institutional, Invited Speaker: Merck; Non-Financial Interests, Institutional, Invited Speaker: Ipsen; Non-Financial Interests, Institutional, Invited Speaker: Five Prime; Non-Financial Interests, Institutional, Invited Speaker: Gilead; Non-Financial Interests, Institutional, Invited Speaker: Arcus; Non-Financial Interests, Institutional, Invited Speaker: Astellas; Non-Financial Interests, Institutional, Invited Speaker: Molecular Templates; Non-Financial Interests, Institutional, Invited Speaker: Lilly; Non-Financial Interests, Institutional, Advisory Role: Amgen; Non-Financial Interests, Institutional, Advisory Role: AstraZeneca; Non-Financial Interests, Institutional, Advisory Role: Daiichi; Non-Financial Interests, Institutional, Advisory Role: Bayer; Non-Financial Interests, Institutional, Advisory Role: BMS; Non-Financial Interests, Institutional, Advisory Role: Merck; Non-Financial Interests, Institutional, Advisory Role: Ipsen; Non-Financial Interests, Institutional, Advisory Role: Five Prime; Non-Financial Interests, Institutional, Advisory Role: Gilead; Non-Financial Interests, Institutional, Advisory Role: Arcus; Non-Financial Interests, Institutional, Advisory Role: Astellas; Non-Financial Interests, Institutional, Advisory Role: Molecular Templates; Non-Financial Interests, Institutional, Advisory Role: Array; Non-Financial Interests, Institutional, Advisory Role: Lilly; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Institutional, Research Grant: Five Prime; Financial Interests, Institutional, Research Grant: Gilead; Financial Interests, Institutional, Research Grant: Arcus; Financial Interests, Institutional, Research Grant: Astellas; Financial Interests, Institutional, Research Grant: Molecular Templates; Financial Interests, Institutional, Research Grant: Roche/Genentech; Financial Interests, Institutional, Research Grant: Array/Pfizer. C. Fountzilas: Non-Financial Interests, Institutional, Other, Has received research support: National Cancer Comprehensive Cancer Network/Taiho Oncology; Non-Financial Interests, Institutional, Other, Has received research support: Merck; Non-Financial Interests, Institutional, Other, Has received research support: Taiho Oncology; Financial Interests, Institutional, Research Grant, Has received research support (paid to institute): Pfizer Inc; Financial Interests, Institutional, Advisory Role, Is a consultant (past) for AstraZeneca outside of the scope of the submitted work (fees paid to the institute): AstraZeneca. N. Bahary: Non-Financial Interests, Institutional, Advisory Role, Consultant: AstraZeneca; Non-Financial Interests, Institutional, Advisory Role, Consultant: Exelixis; Non-Financial Interests, Institutional, Advisory Role, Consultant: BMS; Financial Interests, Institutional, Advisory Role, Consultant: Thermo Fisher. T.M. Mercada: Non-Financial Interests, Institutional, Advisory Role: Amgen; Non-Financial Interests, Institutional, Advisory Role: Baxter; Non-Financial Interests, Institutional, Advisory Role: Celgene; Non-Financial Interests, Institutional, Advisory Role: Incyte; Non-Financial Interests, Institutional, Advisory Role: Q&D Therapeutics; Non-Financial Interests, Institutional, Advisory Role: Serviere; Non-Financial Interests, Institutional, Advisory Role: Shire; Financial Interests, Institutional, Funding: AstraZeneca; Financial Interests, Institutional, Funding: BeiGene; Financial Interests, Institutional, Funding: Celgene. P.M. Peterson: Non-Financial Interests, Institutional, Full or part-time Employment: Eli Lilly & Company. M. Ceccarelli: Non-Financial Interests, Institutional, Full or part-time Employment: Eli Lilly & Company. U. Pelzer: Non-Financial Interests, Institutional, Invited Speaker: Merck; Non-Financial Interests, Institutional, Invited Speaker: AstraZeneca; Non-Financial Interests, Institutional, Invited Speaker: Celgene; Non-Financial Interests, Institutional, Invited Speaker: Bristol-Myers Squibbb; Non-Financial Interests, Institutional, Invited Speaker: Lilly; Non-Financial Interests, Institutional, Invited Speaker: Servier; Non-Financial Interests, Institutional, Invited Speaker: Roche; Non-Financial Interests, Institutional, Invited Speaker: Sanofi-Aventis; Non-Financial Interests, Institutional, Invited Speaker: Shire; Non-Financial Interests, Institutional, Invited Speaker: Bbraun; Non-Financial Interests, Institutional, Other, Research support: Merck; Non-Financial Interests, Institutional, Other, Research support: AstraZeneca; Non-Financial Interests, Institutional, Other, Research support: Celgene; Non-Financial Interests, Institutional, Other, Research support: Bristol-Myers Squibbb; Non-Financial Interests, Institutional, Other, Research support: Lilly; Non-Financial Interests, Institutional, Other, Research support: Servier; Non-Financial Interests, Institutional, Other, Research support: Roche; Non-Financial Interests, Institutional, Other, Research support: Sanofi-Aventis; Non-Financial Interests, Institutional, Other, Research support: Shire; Non-Financial Interests, Institutional, Other, Research support: Bbraun; Non-Financial Interests, Institutional, Other, Research support: Amgen. All other authors have declared no conflicts of interest.