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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Randomised phase II study of second-line olaratumab with mitoxantrone/prednisone versus mitoxantrone/prednisone alone
Oliver W Hakenberg1, Jose Luis Perez-Gracia2, Daniel Castellano3
1Department of Urologie, Universitätsmedizin Rostock, Rostock, Germany.
Introduction:
Platelet-derived growth factor receptor-α (PDGFRα) is expressed in primary prostate adenocarcinoma and in associated skeletal metastases. Olaratumab is a fully human monoclonal antibody that binds PDGFRα and blocks downstream signalling. This phase II study assessed the efficacy and safety of olaratumab in combination with mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after docetaxel.
Methods:
Patients were randomised to receive 21-d cycles of olaratumab (15 mg/kg, Days 1 and 8) plus mitoxantrone (12 mg/m2, Day 1) and prednisone (5 mg, twice daily) or M/P alone. Progression-free survival (PFS) was the primary end-point. Secondary end-points included overall survival (OS), safety, and circulating tumour cell (CTC) counts.
Results:
A total of 123 patients were randomised, 63 to olaratumab + M/P and 60 to M/P. Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P (hazard ratio [HR] = 1.29; 95% confidence interval [CI] = 0.87-1.90). Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P (HR = 1.08; 95% CI = 0.72-1.61). Both treatment arms had similar toxicity profiles; neutropenia (24% versus 15%), anaemia (13% versus 14%) and fatigue (11% versus 9%) (olaratumab + M/P versus M/P, respectively) were the most common grade ≥3 events. High CTC count was associated with poorer OS in both arms. Patients with very high cell counts (>37 cells/7.5 ml) exhibited improved OS with olaratumab + M/P (interaction P = 0.043).
Conclusions:
Olaratumab + M/P had an acceptable safety profile but did not improve the efficacy of M/P chemotherapy. Further study with selected patient populations and earlier in the disease course might be considered.
Insights
Olaratumab combined with chemotherapy did not improve outcomes for metastatic castration-resistant prostate cancer patients. Further research in specific patient groups may be warranted.
Area of Science:
- Oncology
- Pharmacology
Background:
- Platelet-derived growth factor receptor-α (PDGFRα) is present in prostate adenocarcinoma and bone metastases.
- Olaratumab is a monoclonal antibody targeting PDGFRα, inhibiting downstream signaling.
Purpose of the Study:
- To evaluate the efficacy and safety of olaratumab plus mitoxantrone and prednisone (M/P) versus M/P alone in patients with metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel therapy.
Main Methods:
- Phase II randomized study involving 123 patients.
- Patients received either olaratumab + M/P or M/P alone.
- Primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS) and safety.
Main Results:
- Median PFS was 2.3 months for olaratumab + M/P and 2.4 months for M/P.
- Median OS was 14.2 months for olaratumab + M/P and 12.8 months for M/P.
- Similar toxicity profiles were observed; neutropenia, anemia, and fatigue were common grade ≥3 events. Patients with very high circulating tumor cell (CTC) counts showed improved OS with olaratumab + M/P.
Conclusions:
- Olaratumab + M/P demonstrated an acceptable safety profile but did not enhance the efficacy of M/P chemotherapy.
- Further investigation in selected patient populations and earlier disease stages may be beneficial.
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