Platinum Priority – EditorialReferring to the article published on pp. 822–830 of this issue.A “Tail” of Immunotherapy in Metastatic Prostate Cancer
Section snippets
Radiotherapy plus immunotherapy
Preclinical and clinical evidence supports the combination of radiation and immunotherapy, although clear evidence of a true abscopal effect in human randomized controlled trials remains elusive. CA184-043 is similar in some respects to the PACIFIC trial in non–small-cell lung cancer, a randomized phase 3 trial of durvalumab after chemoradiation that showed significant improvements in OS [4] with CPI following treatment with both cytotoxic chemotherapy and radiation. As radiation does,
Reducing early OS declines
Both the CA184-043 and CA184-095 trials showed early lowering of OS curves when compared to the control groups; while not universally seen with immunotherapy, this has been seen in other trials with CPI [8]. In several immunotherapy trials, a disconnect between PFS and OS can also be seen. The reasons for such findings are varied and complex, but no doubt encompass both drug-mediated toxicity issues and delayed onset and/or the effect of antitumor responses in the setting of progressive
Optimal timing of immunotherapy
The initial report on CA184-043 suggested that ipilimumab might provide the most benefit in patients with favorable prognostic features: a post hoc analysis revealed median OS of 22.7 mo versus 15.8 mo in the placebo group (p = 0.038). Similarly, an analysis of patients treated with sipuleucel-T in the IMPACT trial showed the greatest increase in OS for the lowest prostate-specific antigen quartile versus the highest when compared to the control group [10]. Along with numerous preclinical
References (10)
- et al.
Final analysis of the ipilimumab versus placebo following radiotherapy phase III trial in postdocetaxel metastatic castration-resistant prostate cancer identifies an excess of long-term survivors
Eur Urol
(2020) - et al.
Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial
Lancet Oncol
(2014) - et al.
Lower baseline prostate-specific antigen is associated with a greater overall survival benefit from sipuleucel-T in the Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial
Urology
(2013) - et al.
Randomized, double-blind, phase III trial of ipilimumab versus placebo in asymptomatic or minimally symptomatic patients with metastatic chemotherapy-naive castration-resistant prostate cancer
J Clin Oncol
(2017) - et al.
Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer
N Engl J Med
(2017)
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Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach
2023, Cell Reports MedicineIL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC)
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2021, International Journal of Molecular SciencesUpdates on molecular and biochemical development and progression of prostate cancer
2021, Journal of Clinical Medicine