A randomised non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer

Cixutumumab, a human monoclonal antibody (HuMAb), targets the insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vascular endothelial growth factor receptor-2. A non-comparative randomised phase II study evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC).

Men with progressive mCRPC during or after docetaxel therapy received mitoxantrone 12mg/m(2) on day 1 and prednisone 5mg twice daily and were randomised 1:1 to receive either cixutumumab or ramucirumab 6mg/kg intravenously weekly in a 21-day cycle. Primary end-point was composite progression-free survival (cPFS). Secondary end-points included safety, response, radiographic progression-free survival (PFS) and overall survival (OS). Sample size was based on a 50% increase in median cPFS from 2. 6 (MP) to 3. 9months (either combination).

132 men were treated (66 per arm). Median cPFS was 4. 1months (95% confidence interval (CI), 2. 2-5. 6) for cixutumumab and 6. 7months (95% CI, 4. 5-8. 3) for ramucirumab. Median time to radiographic progression was 7. 5months for cixutumumab and 10. 2months for ramucirumab, with a median OS of 10. 8 and 13. 0months, respectively. Fatigue was the most frequent adverse event (AE). Incidence of most non-haematologic grade 3-4 AEs was <10% on both arms. Grade 3 cardiac dysfunction occurred in 7. 6% of patients on ramucirumab.

Combinations of cixutumumab or ramucirumab plus MP were feasible and associated with moderate toxicities in docetaxel-pretreated men with mCRPC. Of the two regimens, the ramucirumab regimen is worthy of further testing based on the observed cPFS relative to the historical control.

European journal of cancer (Oxford, England : 1990). 2015 Jun 13 [Epub]

Maha Hussain, Dana Rathkopf, Glenn Liu, Andrew Armstrong, Wm Kevin Kelly, Anna Ferrari, John Hainsworth, Adarsh Joshi, Rebecca R Hozak, Ling Yang, Jonathan D Schwartz, Celestia S Higano

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States. Electronic address: mahahuss@umich. edu. , Memorial Sloan-Kettering, New York, NY, United States. , University of Wisconsin, Carbone Cancer Center, Madison, WI, United States. , Duke Cancer Institute and Duke Prostate Center, Duke University, Durham, NC, United States. , Thomas Jefferson University, Philadelphia, PA, United States. , New York University Clinical Cancer Center, New York, NY, United States. , Sarah Cannon Research Institute, Nashville, TN, United States. , Eli Lilly and Company, Bridgewater, NJ, United States. , Eli Lilly and Company, Indianapolis, IN, United States. , Eli Lilly and Company, Bridgewater, NJ, United States. , Eli Lilly and Company, Bridgewater, NJ, United States. , University of Washington, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.