Intrinsic tumour biology may be predictive of treatment response in prostate cancer

Molecular determinants may help to identify patients that will derive the best responses to apalutamide for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). This was concluded based on data from the biomarker cohort of the phase 3 SPARTAN trial.

The SPARTAN trial (NCT01946204) was a multicentre, randomised, double-blinded, phase 3 trial investigating apalutamide for the treatment of nmCRPC [1]. Included men (n=1,207) were randomised 1:2 to receive either apalutamide plus androgen deprivation therapy (ADH; n=401) or placebo plus ADH (n=806) until disease progression, withdrawal of consent, unacceptable toxicity, or death. At the primary endpoint analysis presented at ASCO 2020 and published in the New England Journal of Medicine, both metastasis-free survival and overall survival were significantly improved in the apalutamide arm [2,3].

Prof. Felix Feng (University of California San Francisco, USA) presented results from his team’s analysis of the molecular signatures obtained from the biomarker cohort of the SPARTAN trial (n=233). For this analysis, participants were subdivided into those with early progression (EP) of the disease and those who were long-term responders (LTR). Using archival tissue samples from the biomarker cohort of the SPARTAN trial, researchers aimed to identify molecular signatures associated with either EP or LTR responses to treatment – either by apalutamide (n=60) or placebo (n=37).

Patients with EP or LTR had similar baseline characteristics. Increased immune activity, decreased tumour vascularisation, or decreased proliferative capacity at baseline were associated with LTR in the apalutamide group but not the placebo group (see Table). The inverse was true for EP in the apalutamide group, while increased hormonal independence or metastatic capacity at baseline was associated with EP in the placebo group. Tumours with increased expression of signatures suggestive of T-cell proliferation demonstrated a more favourable response to apalutamide; this response was true in both basal and luminal tumours.

Table: Molecular signatures in the apalutamide + ADT group. Based on [1]



* Reached nominal statistical significance in Cox regression analysis only.
EP, early progression; ICOS, inducible co-stimulatory; IL, interleukin; LTR, long-term responders; TAP2, transporter associated with processing 2.

Prof. Feng concluded that these molecular signatures may be useful to predict which patients with nmCRPC will derive the most favourable treatment responses to apalutamide and other androgen receptor signal inhibitors.

1. Feng F. Molecular determinants associated with long-term response to apalutamide in nonmetastatic castration-resistant prostate cancer (nmCRPC). Abstract 8, ASCO Genitourinary Cancers Symposium, 11–13 February 2021.
2. Small EJ, et al. Abstract 5516, ASCO Virtual Meeting, 29–31 May 2020.
3. Smith MR, et al. N Engl J Med. 2018; 378: 1408–1418.

 

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Posted on 24 March 202117 May 2024