1053PD - Finite androgen deprivation therapy (ADT) plus ipilimumab (IPI) in men with hormone-naïve metastatic prostate cancer (HN-mPCa)

Date 28 September 2014
Event ESMO 2014
Session Immunotherapy of cancer
Topics Anti-Cancer Agents & Biologic Therapy
Prostate Cancer
Cancer Immunology and Immunotherapy
Presenter Sumit Subudhi
Citation Annals of Oncology (2014) 25 (suppl_4): iv361-iv372. 10.1093/annonc/mdu342
Authors S.K. Subudhi1, A. Aparicio1, A.J. Zurita1, J.C. Araujo1, P.G. Corn1, S. Tu1, X. Wang2, D.R. Harris1, K. Winslow1, J. Gao1, C.J. Logothetis1, P. Sharma1
  • 1Genitourinary Medical Oncology, UT MD Anderson Cancer Center, 77030-3721 - Houston/US
  • 2Quantitative Sciences, UT MD Anderson Cancer Center, 77030-3721 - Houston/US

 

Abstract

Aim

ADT increases the thymic output of T cells, antigen-specific T cell responses and infiltration of T cells into the prostate. IPI is an immunotherapy that blocks the function of an immune checkpoint, cytotoxic T-lymphocyte antigen 4 (CTLA-4), and promotes durable antitumor responses. We hypothesized that the effects of ADT plus IPI would be synergistic and assessed this in men with HN-mPCa.

Methods

We piloted a single-arm, single-center, observational study from July 2011 to June 2013 to determine if finite ADT plus IPI is safe, estimate efficacy and link clinical outcomes to immunologic changes in men with HN-mPCa. ADT was administered for only 8 months with concurrent IPI (10 mg/kg) for up to 4 doses at 4-weeks intervals. The primary endpoint was to estimate the rate of undetectable PSA at 7 months post-treatment initiation.

Results

We enrolled 30 pts of which 25 (83%) were evaluable for efficacy and 27 (90%) for safety. Median age was 62 and Gleason score ≥8 in 89% of patients. Bone metastases were most common (85%), followed by lymph nodes (48%), and then lungs (7%). Eleven of 25 (44%) pts achieved a PSA ≤0.2 ng/ml 7 months after treatment initiation. Median time to PSA progression was 330 days (130, 476) from the PSA nadir. Two of 25 (8%) pts achieved complete radiographic and PSA responses ongoing for 944 and 364 days, respectively. Trial was closed when 12/27 (44%) pts developed Grade ≥3 toxicity, a predetermined stopping criterion. Most common Grade ≥3 immune-related adverse events (irAEs) included liver (15%), GI (11%), endocrine (11%), dermatologic (4%) and were mostly reversible using standard IPI management algorithms.

Conclusions

This pilot study suggests the combination of finite ADT plus IPI can induce “curative” responses in a subset of pts with HN-mPCa. Subgroup analyses indicate that clinical benefit correlates with lower tumor burden as anticipated per disease biology. irAEs are likely to occur and require careful management. To minimize irAEs consideration we will test ADT with IPI at a dose of 3 mg/kg. Immunologic characterization of available tumor specimens (to be presented at the meeting) will lead to understanding interactions between ADT and IPI and guide identification of pts likely to benefit.

Disclosure

C.J. Logothetis: I have consultant/Advisory Role, Honoraria, and Research Funding for the following: Astellas Novartis Bristol-Myers Squibb Johnson & Johnson Excelixis Pfizer Sanofi Bayer Takeda; P. Sharma: I am a paid consultant for GlaxoSmithKline, Pfizer, Dendreon, Bristol-Myers Squibb, Jounce, Helsinn, MedImmune. I have ownership interest in Jounce. All other authors have declared no conflicts of interest.