CAPTURE Trial Reveals BRCA Mutations Linked to Worse Outcomes in mCRPC

Conceptual image for viral ethiology of prostate cancer. 3D illustration showing viruses infecting prostate gland which develops cancerous tumor: © Dr_Microbe - stock.adobe.com

Patients with metastatic castration-resistant prostate cancer (mCRPC) in the BRCA subgroup had worse outcomes compared with those in non-BRCA subgroups, either homologous recombination repair (HRR) non-BRCA or non-HRR, according to results of the CAPTURE trial.¹

These data come from 729 patients with mCRPC who were pooled for CAPTURE from 4 multicenter, observational studies (PROREPAIR-B [NCT03075735], PROSENZA [NCT02922218], PROSTAC [NCT02362620] and PROSABI [NCT02787837]). A total of 96 (13.2%), 127 (17.4%) and 506 (69.4%) of the 729 patients were in the BRCA, HRR non-BRCA, and non-HRR subgroups, respectively.

Significantly worse radiographic progression-free survival (rPFS), time to second objective disease progression (PFS2), and overall survival (OS) were seen among patients with BRCA mutations vs the full non-BRCA mutation population (P <.05). Additionally, worse PFS2 and OS rates were seen in this group compared with those who had other HRR mutations but were BRCA wild-type (P <.05).

“The initial results suggest that BRCA patients, independent of germline or somatic origin, have shorter rPFS, PFS2, and OS, so they have worse outcomes…than HRR non-BRCA [patients], and HRR non-BRCA patients are worse than those without mutations,” David Olmos, MBBS, MSc, PhD, Hospital Universitario 12 de Octubre, Madrid, Spain, told Targeted Oncology^TM.

This study sought to investigate the prevalence and outcomes associated with somatic/germline HRR alterations. In particular, experts looked at BRCA1/2 mutations in patients with mCRPC starting treatment in the first line with androgen receptor signaling inhibitors or taxanes.

“The main finding is that our study demonstrates that BRCA1/2 alterations, both germline and somatic, are associated with shorter radiographic progression-free survival, PFS2, and OS. The baseline characteristics between BRCA, HRR, or non-BRCA patients did not differ in our study. [Patients with] BRCA [mutations] also have worse outcomes than patients who have a mutation in other HRR genes different from BRCA. But still, we need to further clarify the particular contribution of some of these HRR genes,” explained Olmos.

Enrollment in the study was open to male patients aged 18 years and older who needed first-line treatment with androgen receptor signaling inhibitors or taxanes and those who had adequate tumor samples, as well as biomarker panel results. Once enrolled, patients were divided based on somatic/germline alteration(s) into different subgroups of the trial, including those with BRCA1/2 mutations (BRCA), those with HRR mutations except BRCA1/2 (HRR non-BRCA), and those without HRR alterations (non-HRR). If patients did not have a BRCA1 or BRCA2 mutation, they were classified as non-BRCA.

Experts assessed the end points of rPFS, PFS2, and OS.

In the study, 47.2% of patients presented with metastatic prostate cancer at diagnosis, and the majority of patients received androgen deprivation therapy (ADT) alone for metastatic hormone-sensitive prostate cancer (mHSPC). Only 8.1%, 1.0% and 0.1%, respectively, received ADT with docetaxel, ADT combined with androgen receptor signaling inhibitors, or ADT combined with docetaxel and androgen receptor signaling inhibitors. The median time from ADT to castration resistance was 25.0 months.

Additionally, the median age of patients at the start of first-line treatment was 72.2 years. A total of 13.3% of patients had visceral metastases, and 53.1% had an ECOG score ≥1.

Among all of the patients included in the study, 60.4% received first-line treatment for mCRPC with androgen receptor signaling inhibitors. The other 39.6% of patients were treated with taxanes in the first line, including docetaxel (37.6%) and cabazitaxel (2.1%). Most patients (80.7%) were given a second-line treatment. Of these patients, 52.3% received docetaxel. Additionally, 57.5% of patients went on to receive third-line treatment.

Overall, this study shows the negative impact of BRCA1/2 alterations on outcomes of patients with mCRPC, regardless of somatic/germline origin. It is crucial to identify these mutations early and use effective therapies to best improve patients' prognosis.

“Although limited, our exploratory analysis suggests that when we analyze BRCA1 and BRCA2, together, germline and somatic alterations are the same,” added Olmos. “The most important is that we need to identify these patients, because we know that we can deliver more precise patient care when we identify those mutations.”

REFERENCE:

Olmos D, Lorente D, Alameda D, et al. Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes. Ann Oncol. Published online February 27, 2024. doi:10.1016/j.annonc.2024.01.011