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 < 0.0001) disease. Disease volume was a better fit to survival data than risk group (AIC 878.3 vs. 889.2). Compared to patients achieving undetectable PSA at 28 weeks, inferior survival was observed in patients whose PSA was >0.2 to ≤4.0 ng/mL (HR 3.72 [1.99–6.95]; p < 0.0001) or >4.0 ng/mL (HR 7.13 [4.24–11.9]; p < 0.0001).

Conclusions

In new metastatic hormone-sensitive prostate cancer, addition of cixutumumab to androgen deprivation did not improve survival. Baseline risk and disease volume carried prognostic value for this distinct trial population, although disease volume added more prognostic information. PSA treatment response was a strong intermediate endpoint for survival.

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Acknowledgements

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health, the Clinical Research Division of the Fred Hutchinson Cancer Research Center, and in part by ImClone Systems (subsidiary of Eli Lilly and Company). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under award numbers CA180888, CA180819, CA180818, CA180828, CA233328, CA46368, CA180801, CA180835, CA35421, CA180834, CA142559, CA35281, CA35090, CA37981, CA45807, CA46282, CA180846, CA180830, CA35431, CA58416, CA63848, CA63844, CA12644, CA11083, CA35178, CA67575, and CA45808, by the Clinical Research Division of the Fred Hutchinson Cancer Research Center, and in part by ImClone Systems (subsidiary of Eli Lilly and Company).

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Correspondence to Evan Y. Yu.

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Conflict of interest

EY has received research support from Dendreon, Merck, and Seattle Genetics and consulted for Bayer, Clovis, Dendreon, Janssen, and Merck. NA has consulted for Astellas, AstraZeneca, BMS, Bayer, Clovis, Eisai, Exelixis, EMD Serono, Eli Lilly, Foundation Medicine, Genentech, Janssen, Merck, Novartis, Nektar, Pfizer, and Pharmacyclics. HC has received research support from Clovis, Janssen, Medivation, and Sanofi. MH has received honoraria from Aptitude Health, Astellas, Epics, Genentech, PER, Research to Practice, and Sanofi/Genzyme, consulted for AstraZeneca, Bayer, and Pfizer, received research support from AstraZeneca, Bayer, Genentech, and Pfizer, and received travel and accommodation support from Astellas, AstraZeneca, Bayer, Genentech, and Pfizer. DQ has consulted for Astellas, Bayer, Janssen, Pfizer, Sanofi, and AstraZeneca. The other authors declare that they have no conflict of interest.

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Wong, R.L., Duong, M.T., Tangen, C.M. et al. Survival outcomes and risk group validation from SWOG S0925: a randomized phase II study of cixutumumab in new metastatic hormone-sensitive prostate cancer. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-0210-x

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