Watch these video interviews on the iPad edition of this issue conducted by OT reporter Peter Goodwin:
PSMA Conjugate Shows Promise
Daniel Petrylak, MD, Professor of Medicine (Medical Oncology) and of Urology and Co-Director of the Signal Transduction Research Program at Yale University Medical Center, reported on a prostate-specific membrane antigen (PSMA) conjugate showing promise for men with metastatic castration-resistant taxane-refractory prostate cancer that progressed despite treatment with a taxane (Abstract 83). The immunoconjugate consists of an antibody to PSMA bonded to the microtubule-disrupting molecule monomethyl auristatin E (MMAE) and was generally well tolerated, he said, noting that testing is also ongoing in taxane-naive patients.
Phase III Data for Orteronel
Robert Dreicer, MD, Chair of the Department of Solid Tumor Oncology at Taussig Cancer Institute of the Cleveland Clinic, reported on a Phase III study of orteronel, a non-steroidal selective inhibitor of 17,20-lyase, which failed to produce a significant improvement in overall survival in 1,099 patients randomized to treatment with that "abiraterone-like" agent in comparison with placebo (Abstract 7). Still, radiographic progression-free survival was extended, and he said that despite the negative finding, such research makes him optimistic about continued progress in this challenging clinical situation.
'New-Generation' Androgen-Deprivation Therapy
Heather H. Cheng, MD, PhD, Senior Research Fellow at Fred Hutchinson Cancer Research Center, presented a multicenter retrospective study about response to enzalutamide after prior abiraterone therapy in men with castration-resistant metastatic prostate cancer (Abstract 18). Approximately 40 percent of patients responded to use of this "new-generation" androgen-deprivation therapy, resulting in a PSA decline of at least 30 percent. This suggests, she said, that there is a subset of men with distinct biological resistance pathways.
When Gleason Score Does Not Predict Response
Karim Fizazi, MD, PhD, Professor of Medicine and Head of the Department of Cancer Medicine at Institut Gustave Roussy in France, presented a study showing that the Gleason score at initial diagnosis was not predictive of response to abiraterone in men with metastatic castration-resistant prostate cancer. In the video, he discusses the study, a pooled analysis of three trials of abiraterone therapy, and the implications for using new-generation androgen-deprivation therapy in the advanced stages of prostate cancer (Abstract 20).
Plasma and Tumor Biomarkers That Could Help Guide Therapy
Bernard Escudier, MD, Head of the French Immunotherapy Unit at Institut Gustave Roussy, presented a study showing that plasma and tumor biomarkers including FGF, C-KIT, and VEG-F provided prognostic information that could help guide therapy. In the video he discusses the results from the biomarker analysis of the multinational Phase III randomized GOLD study (Abstract 473) looking at "third-line" therapy for metastatic renal cell carcinoma with the FGF-directed agent dovitinib compared with sorafenib in patients with metastatic renal cell carcinoma after one prior VEGF pathway-targeted therapy and one prior mTOR-inhibitor therapy.
High baseline cKIT and low baseline FGF2, HGF, PlGF, sVEGFR1, VEGFA, and VEGFD levels were associated with longer overall survival in patients treated with either sorafenib or dovitinib. The analysis also concluded that baseline plasma biomarkers are prognostic but not predictive in the third-line setting.
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