The 2023 ESMO annual meeting included a session on prostate cancer, featuring a presentation by Dr. Steven M. Yip discussing real world treatment patterns of metastatic prostate cancer with enhanced access to HRR genomic testing and PARP inhibitors. An estimated 25% of individuals with metastatic castration-resistant prostate cancer(mCRPC) diagnosis possess either germline or somatic alterations in the DNA damage repair genomic pathway, which may have an impact on prognosis and treatment, as well as familial screening of family members.
PARP inhibitor therapy alone and in combination with ARPIs improve outcomes in individuals with HRR gene alterations, particularly BRCA1 and BRCA 2 mutations. Successful management of metastatic prostate cancer then relies on identification of actionable genomic alterations in HRR genes, and the availability of targeted therapies which can precisely inhibit the deleterious effects of these genomic alterations. At the 2023 ESMO annual congress, Dr. Yip and colleagues reported results of real world outcomes and impact of streamlined access to a biomarker driven treatment approach.
In a multicenter prospective metastatic prostate cancer cohort study, cell free DNA next generation sequencing was performed using accredited assays (BC Cancer, Foundation Medicine, and Alberta panel). Time to CRPC was compared between HRR alterations and HRR negative/unknown status using the log rank test. In olaparib treatment patients, ≥50% PSA decline, radiographic progression free survival (rPFS), serious adverse events, and overall survival (OS) were examined.
There were 119 patients included in this multicenter prospective Alberta cohort, with the following baseline characteristics:
There were 41 (35%) patients identified with HRR alterations (23 BRCA2, 14 ATM, 5 CDK12, 3 CHEK2, 2 PPP2R2A, 1 BRCA1, 1 PALB2):
In 28 HRR alteration patients with genomic alterations treated with olaparib (19 BRCA2, 8 ATM, 1 BRCA1), real world response and outcomes data on olaparib were compared to data in PROfound,1 with a notable decrease in objective response rate, as well as PFS and OS:
Serious adverse events occurred in 39% of patients and 4 patients required transfusion for anemia. The 28 HRR alterations patients that received olaparib demonstrated a trend towards improved OS from mCRPC compared to HRR alterations patients without PARP inhibitors (38.1 vs 17.4 months, p = 0.20). OS from mCRPC was similar in HRR negative/unknown status and olaparib treatment HRR alterations patients (37.4 vs 38.1 months, p = 0.70):
Overall, 29% of patients received olaparib >= 30 days beyond progression (biochemical or imaging-based) and median duration of treatment beyond progression was 4.0 months (range: 1.5 – 8.7 months). Additionally, 8 patients received additional systemic therapy post-olaparib: 6 patients received single-agent taxane chemotherapy, and 2 patients received combination platinum + taxane chemotherapy.
Dr. Yip concluded his presentation discussing real world treatment patterns of metastatic prostate cancer with enhanced access to HRR genomic testing and PARP inhibitors with the following take-home points:
- In this study of heavily pre-treated mPCa patients, real world rPFS and OS on olaparib were reduced compared to clinical trials
- These results demonstrate that a biomarker driven treatment approach and earlier access to PARP inhibitors may improve outcomes in HRR alteration patients
- Similar OS was seen in olaparib treatment HRR alterations and HRR negative/unknown status patients, despite historically poorer prognosis in HRR alterations patients
- Earlier access to olaparib, and thus earlier genomic testing, may improve real world outcomes
Presented by: Steven M. Yip, MD, MSc, Tom Baker Cancer Centre, Calgary, Alberta, Canada
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2023 European Society of Medical Oncology (ESMO) Annual Meeting, Madrid, Spain, Fri, Oct 20 – Tues, Oct 24, 2023.
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