97: Four-Year PSA Response Rate as a Predictive Measure in Intermediate Risk Prostate Cancer Treated with Ablative Therapies: The Sprat Analysis

58 Background: Castrating androgen deprivation therapy (ADT) is standardly prescribed in combination with radiation therapy (RT) for intermediate or high-risk prostate cancer (PCa). ADT is associated with multiple side effects including weight gain, loss of libido, hot flashes and muscle atrophy. In contrast, enzalutamide monotherapy is associated with much fewer side effects. Methods: At Dana-Farber/ Harvard Cancer Center we performed an open label phase II study of enzalutamide for 6 months as neo- and adjuvant treatment for intermediate risk PCa patients (NCCN criteria) receiving RT. The primary endpoint was the proportion of patients achieving a PSA response of ≤0.2 . This endpoint is predictive of long term PSA response in a similar risk-group of patients treated with RT and ADT. PSA values were obtained at baseline and monthly on 6 cycles of enzalutamide (160mg/day). 79.2 Gy in 44 fractions of IMRT was started between 6 and 10 weeks after the initiation of enzalutamide. Quality of life questionnaires, hormone levels and anthropomorphic measurements were obtained. Results: 45 of 60 evaluable patients had a PSA ≤0.2 at the end of 6 months of enzalutamide. With a sample size of 64 evaluable patients, if the number achieving a PSA level is ≤0.2 is 44 or more, the null hypothesis is rejected with a target error rate of alpha = 0.10. Also 54 of 60 evaluable patients had a PSA of ≤0.5ng/ml. Importantly, less than half of the participants experienced erectile dysfunction or decreased libido and these were predominantly grade I. Less than a quarter of patients reported hot flashes (all grade I). Waist circumference did not change with therapy. The most frequent grade 2 or greater events were hypertension and gynecomastia. Testosterone and free testosterone levels rose significantly on enzalutamide therapy. Conclusions: Enzalutamide monotherapy with RT may be as effective as castrating ADT, and associated with fewer side effects. Larger, randomized trials are needed to further evaluate enzalutamide monotherapy, instead of ADT, to be used in combination with RT. Clinical trial information: NCT0208988.

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Functional, Radiological Imaging and Biochemical (PET PSMA, MRI, ADC, PSA) Response and its Correlation in Low and Intermediate Risk Prostate Cancer Treated with SBRT by Robotic Radiosurgery Alone

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2018.07.275 ◽

2018 ◽

Vol 102 (3) ◽

pp. e142-e143

Author(s):

P.S. Sridhar ◽

N. Madhusudhan ◽

K. Roopesh ◽

M. Praveen kumar ◽

G.H. Abilash ◽

...

Keyword(s):

Prostate Cancer ◽

Intermediate Risk ◽

Radiological Imaging ◽

Robotic Radiosurgery ◽

Risk Prostate Cancer ◽

Psa Response

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Phase I/II open label nonrandomized safety and efficacy study of the viral vectored ChAdOx1-MVA 5T4 immunotherapy in combination with PD-1 checkpoint blockade in intermediate-risk localized or locally advanced prostate cancer and advanced metastatic prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.tps3170 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. TPS3170-TPS3170

Author(s):

Mark Tuthill ◽

Federica Cappuccini ◽

Richard John Bryant ◽

Ian Poulton ◽

Emily Pollock ◽

...

Keyword(s):

Prostate Cancer ◽

Phase I ◽

Cancer Patients ◽

Advanced Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Response Rate ◽

Intermediate Risk ◽

Open Label ◽

Safety And Efficacy ◽

Risk Prostate Cancer

TPS3170 Background: Antigen-specific immunotherapy (Sipuleucel-T) is licenced for the treatment for castrate resistant prostate cancer, but has modest clinical efficacy and is complex to administer to patients. New therapeutic antigen-specific approaches are required to generate and sustain therapeutic immune responses against tumour specific antigens in men with early and advanced prostate cancer. We have previously reported immunogenicity and efficacy data of a novel viral vectored vaccines-based immunotherapy based on two replication-deficient viruses, chimpanzee adenovirus (ChAdOx1) and MVA, targeting an oncofetal self-antigen 5T4, administered as a single agent and in combination with anti-PD-1 in mouse tumour models. We tested this immunotherapy alone in a first-in-human trial, VANCE (NCT02390063), in intermediate risk prostate cancer patients. Based on encouraging safety and exceptional T cell immunogenicity of the VANCE study, the phase I/II trial, ADVANCE (NCT03815942) is being undertaken to test the immunotherapy safety and efficacy in combination with PD-1 blockade in intermediate risk disease and metastatic prostate cancer. Methods: Study design: ADVANCE, an open label non-randomised phase I/II study, will recruit 12 patients with intermediate-risk prostate cancer patients (Gleason score ≤ 7, local tumour stage ≤T3c, PSA≤ 20 ng/ml) scheduled to undergo radical prostatectomy (Cohort 1) and 24 mCRPC patients with disease progression on anti-androgen therapy with either enzalutamide or abiraterone (Cohort 2). Cohort 1 will receive one cycle of ChAdOx1-MVA 5T4 immunotherapy and a single nivolumab infusion. Cohort 2 will receive 2 cycles of ChAdOx1-MVA 5T4 vaccination and three nivolumab infusions. Primary endpoint: Cohort 1 - PSA change from baseline to surgery, Cohort 2 – composite response rate measured as either ≥50% reduction of circulating tumour DNA or ≥50% serum PSA decrease from baseline at 24-week assessment and the maximal response rate. Secondary and exploratory endpoints include 5T4-specific immune response in the periphery, progression-free and overall survival and reduction of circulating tumour cells. 23 of planned 24 patients have been enrolled in Cohort 2. Enrolment to the Cohort 1 is ongoing. The data analysis is expected to be completed by Q4 2020 for Cohort 2. Clinical trial information: NCT03815942 .

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