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Real-world analysis of homologous recombination repair (HRR)-mutant metastatic castration-resistant prostate cancer (mCRPC) patients treated with olaparib (Lynparza) reveals how to better and more accurately treat this disease. The need for earlier and more consistent genetic testing was identified.According to real-world analysis data published in 2024 Genitourinary Cancer Symposium.
The study collected information from 192 patients from an electronic database, and the researchers ultimately found that most patients (74.0%) evaluated in the study were tested at or after their mCRPC diagnosis. I discovered. However, only 5.7% of these patients were tested before first-line treatment.
Further investigation revealed that 36.1% of patients had some symptoms. BRCA Mutations (n = 108) had somatic-only testing. 18.5% underwent germline-only testing. 28.7% underwent germline and somatic cell testing. 16.7% had other unconfirmed tests. On the other hand, in non-BRCA In the HRR mutation group (n = 84), 46.4% of patients underwent somatic testing only. 10.7% underwent germline-only testing. 26.2% underwent both germline and somatic cell testing. 16.7% had other unconfirmed tests.
Any BRCA– In the variant group, 75.9% of patients were tested at or after diagnosis, and 3.7% of patients were tested before first-line treatment. The median time from mCRPC diagnosis to testing was 20.7 months.NonBRCA In the HRR mutation group, 71.4% of patients underwent testing at or after mCRPC diagnosis. The median time from diagnosis to biomarker testing was 13.5 months, and 13.3% of these patients underwent testing before first-line treatment.
“HRR test in patients before or during mCRPC” [diagnosis] “This allows olaparib therapy to be administered earlier in the disease course, potentially resulting in greater clinical benefit,” study lead author Daniel J. George, MD, PhD, and colleagues said in a poster presentation. “Based on the expanded FDA label, earlier trials will be required to combine abiraterone and olaparib in patients with: BRCA first line mutation [in] mCRPC. ”
George is Chief of the Division of Urology (GU) Oncology and Professor of Medicine and Surgery at Duke University School of Medicine in Durham, North Carolina.
As nearly a quarter of mCRPC patients carry HRR gene mutations, early germline and somatic testing remains recommended for this patient population. Notably, olaparib is one of the first targeted therapies available for these patients and has shown superior survival outcomes compared to physician-chosen treatments.
Based on this information, the researchers designed a study to evaluate both treatment patterns and genetic testing results in HRR-mutant mCRPC patients previously treated with olaparib monotherapy.
To be eligible for this evaluation, patients must have a confirmed diagnosis of HRR-mutant mCRPC, be 21 years of age or older, and have received olaparib monotherapy after exposure to abiraterone (Zytiga) or enzalutamide (Xtandi). Specifically, HRR mutations were defined as mutations in at least one of the following genes: BRCA1, BRCA2, ATM, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, RAD51B, RAD51C, RAD51D, or RAD54L.
Exclusion criteria include diagnosis of other primary cancers or enrollment in other previous or current interventional clinical trials at or after mCRPC diagnosis. Of note, variation in patient demographics, clinical characteristics, and biomarker testing patterns was allowed in the patient population.
This retrospective, non-interventional study utilized electronic medical record data from the ConcertAI Oncology Dataset. This dataset included information from patients from geographically distinct locations, primarily consisting of community oncology clinics in the United States. At enrollment, patients were divided into one of two groups. BRCA Mutant and non-mutantBRCA HRR mutation.
Data collection began on February 7, 2023 and ended on June 16, 2023. Medical records from patients with diagnosis dates between his 1990 and his 2023.
The median age of all patients enrolled as of the index date was 73 years. The majority of patients in the overall population were white (77.1%), and 68.2% did not identify as Hispanic or Latino. A total of 63.0% of patients had a known stage at initial diagnosis. Of these patients, 1.7% were classified as stage I, 15.7% as stage II, 9.1% as stage III, and 73.6% as stage IV.
Of the 141 patients with documented ECOG performance status (PS), 76.6% had PS 0 or 1, whereas 23.4% had PS 2 or higher. Notably, 88.8% of patients had distant metastases in bone at the index date.
Additionally, 77.6% of patients had a known Gleason score. Of these, 10.1% had a score of 6 or less, 24.2% had a score of 7, and 65.8% had a score of 8 or higher. The median time from diagnosis of mCRPC to completion of patient records was 25.3 months. Median time from index date to end of record was 8.4 months. Median prostate-specific antigen level at index date plus or minus 30 days was 72.2 ng/mL. 31.3% of patients indicated opioid use as of the index date. Of the 145 patients who were in a known treatment setting, 14.5% were treated in an academic setting and 85.5% in a community setting.
In their poster presentation, the researchers further noted that 40.6% of patients received only somatic testing, compared with 15.1% who received germline-only testing, and 15.1% of patients received both germline and somatic testing. It was pointed out that 27.6% of patients received However, her 16.7% of patients had other unconfirmed tests.
Notably, the study authors identified multiple limitations of the study.
- This study was conducted only in patients who received olaparib after treatment with enzalutamide or abiraterone.
- This study only includes patients from the ConcertAI Oncology Dataset, which may differ from the overall mCRPC patient population.
- Most of the patients included in the study were treated in the community, and all patients were treated in the United States.
- The analysis was limited to the range of data available in this dataset.
- Information regarding patients’ reasons for opioid use was not collected.
Overall, this study highlights the need for earlier and more consistent testing for HRR mutations in mCRPC patients.
“Most of the patients in this study were tested and diagnosed with HRR mutations several months after their mCRPC diagnosis. At that time, they had high-level bone metastases, multiple distant metastases, and were on opioid therapy. It is unlikely that the use of olaparib at the beginning of treatment could “benefit from a precision oncology approach,” the study authors concluded.
reference
George DJ, Kariburyo-Yay F, Aggarwal H, et al. Actual homologous recombination repair mutation (HRRm) testing patterns in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib in the United States. J Clin Oncor. 2024;42(supplement):332. doi:10.1200/JCO.2024.42.4_suppl.332
Link to poster: https://d201v5jt9ylckg.cloudfront.net/315/15621/230323/230323_A166_poster_big_1.jpg
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