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Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer.

ABSTRACT: BACKGROUND:Cixutumumab, a monoclonal antibody targeting insulin-like growth factor I receptor, did not improve undetectable prostate-specific antigen (PSA) rate at 28 weeks when combined with androgen deprivation in the randomized phase II SWOG S0925 trial for patients with new metastatic hormone-sensitive prostate cancer. We now present mature survival analyses, along with pre-specified secondary and exploratory endpoints. METHODS:We randomized 210 patients to androgen deprivation with or without cixutumumab, 105 per treatment arm. We used Kaplan-Meier curves to analyze overall survival, radiographic progression-free survival, and castration resistance-free survival by treatment arm, disease volume, and risk group. We explored differences in survival by treatment arm via covariate-adjusted Cox proportional hazards models adjusted for disease volume and risk. RESULTS:No difference was seen between treatment arms in overall survival (HR 1.01 [0.70-1.45]; p?=?0.97), radiographic progression-free survival (HR 1.17 [0.85-1.60]; p?=?0.35), or castration resistance-free survival (HR 1.02 [0.75-1.41]; p?=?0.88). At baseline, 105/198 (53.0%) patients had high-risk features and 119/210 (56.7%) had high-volume disease; 16.7% of patients had discordant classifications of high or low category for risk and volume. Adjusting for risk or volume yielded no differences in overall survival between arms. Inferior survival was observed in high-risk (HR 1.89 [1.29-2.80]; p?=?0.001) and high-volume (HR 2.75 [1.84-4.10]; p?0.2 to ?4.0 ng/mL (HR 3.72 [1.99-6.95]; p?4.0 ng/mL (HR 7.13 [4.24-11.9]; p?

SUBMITTER: Wong RL

PROVIDER: S-EPMC7423720 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer.

Wong Risa L RL Duong Mai T MT Tangen Catherine M CM Agarwal Neeraj N Cheng Heather H HH Vogelzang Nicholas J NJ Hussain Maha M Thompson Ian M IM Quinn David I DI Yu Evan Y EY

Prostate cancer and prostatic diseases 20200213 3

<h4>Background</h4>Cixutumumab, a monoclonal antibody targeting insulin-like growth factor I receptor, did not improve undetectable prostate-specific antigen (PSA) rate at 28 weeks when combined with androgen deprivation in the randomized phase II SWOG S0925 trial for patients with new metastatic hormone-sensitive prostate cancer. We now present mature survival analyses, along with pre-specified secondary and exploratory endpoints.<h4>Methods</h4>We randomized 210 patients to androgen deprivatio ...[more]

PMID: 32055002

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Project description:BACKGROUND:Previous studies suggest circulating, blood-based microRNAs (miRNAs) may serve as minimally invasive prostate cancer biomarkers, however there is limited data from prospective clinical trials. Here, we explore the role of candidate plasma miRNAs as potential biomarkers in the SWOG 0925 randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone in patients with new metastatic hormone-sensitive prostate cancer. METHODS:Correlative biospecimens, including circulating tumor cells (CTCs) and plasma for miRNA analysis, were collected at baseline and after 12 weeks on treatment from 50 patients enrolled on SWOG 0925. Circulating microRNAs were quantified using real-time RT-PCR microRNA array that allowed specific analysis of previously identified candidate miRNAs (miR-141, miR-200a, miR-200b, miR-210, and miR-375) as well as discovery analysis to identify new candidate miRNAs. MiRNA levels were correlated to previously reported CTC counts using CellSearch® (Veridex) and with the primary study outcome of 28-week PSA response (?0.2, 0.2 to ?4.0, or >4.0?ng/mL), previously shown to correlate with overall survival. RESULTS:We observed a correlation between baseline circulating miR-141, miR-200a, and miR-375 levels with baseline CTCs. Baseline miR-375 levels were associated with 28-week PSA response (?0.2, 0.2 to ?4.0, or >4.0?ng/mL, P?=?0.007). Using ROC curve analysis, there was no significant difference between baseline miR-375 and baseline CTC in predicting 28-week PSA response (?0.2 vs >0.2?ng/mL). To discover novel candidate miRNAs, we analyzed 365 miRNAs for association with the 28-week PSA response endpoint and identified new candidate miRNAs along with the existing candidates miR-375 and miR-200b (P?=?0.0012, P?=?0.0046, respectively. CONCLUSIONS:Baseline plasma miR-141, miR-200a, and miR-375 levels are associated with baseline CTC count. Baseline miR-375 was also associated with the trial endpoint of 28-week PSA response. Our results provide evidence that circulating miRNA biomarkers may have value as prognostic biomarkers and warrant further study in larger prospective clinical trials.

Dataset Information

Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer.

Publications

Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer.

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