China's real-world olaparib research data is released, and clinical efficacy adds more evidence

*It is only for medical professionals to read.
The research report shows that mCRPC patients in the real world in China can benefit from olaparib treatment.
October Nanjing, Dangui Piaoxiang, the 28th National Urology Conference on October 22- It was successfully held in Nanjing on the 24th
.

On the occasion of the 40th anniversary of the establishment of the Chinese Medical Association Urology Branch, urology elites from all over the country gathered to share cutting-edge academic progress and clinical practice experience; Professor Xue Wei from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine at the Male Reproductive Oncology Branch The team reported the first real-world study data of olapari orally.
This is the first report of olapari's research data in the Chinese population.
Let's take a look at it
.

Advanced prostate cancer is an important killer of elderly men’s health.
Almost all prostate cancers that have not been cured will eventually progress to the advanced stage of the tumor-metastasis castration resistant prostate cancer (mCRPC)
.

In the mCRPC stage, tumors will exhibit structural and functional abnormalities at the level of a variety of genes, among which homologous recombination repair gene (Homologous Recombination Repair, HRR) mutations are one of the common types of mutations [1]
.

With the emergence of PARP inhibitors targeting HRR mutations, especially in June 2021, the PARP inhibitor olaparib was approved in China for carrying BRCA gene mutations.
Previously, abiraterone or enzalutamide were treated Failed metastatic castration resistant prostate cancer patients, the treatment of advanced prostate cancer patients ushered in a new turn, but there is no data report in Chinese prostate cancer patients
.

Dr.
Dong Baijun from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine reported on the efficacy of olaparib in the real world.
Retrospective research carried out jointly by the two centers
.

Prostate cancer has entered precision diagnosis and treatment.
How to choose a more appropriate treatment for mCRPC patients is currently the topic of most concern to clinicians.
Renji Hospital affiliated to Shanghai Jiaotong University School of Medicine has carried out in-depth exploration on this
.

The previous multi-center small sample of Renji Hospital, Shanghai Jiaotong University School of Medicine, based on the molecular characteristics of peripheral blood ctDNA multi-gene targeted sequencing of mCRPC, found that mCRPC patients have more genomic changes, of which the AR pathway is 56.
7%, DNA The mutation frequency of damage repair pathway genes is 61.
7%, and the neuroendocrine differentiation-related genes TP53 and RB1 are 16.
7% [2]
.

In the follow-up expanded sample mCRPC precision treatment cohort, it was found that the mutation frequency of CDK12 in the Chinese population was significantly higher than that in the European and American populations.
Patients with CDK12 mutations have rapid disease progression and poor response to new endocrine treatments; for mCRPC patients with BRCA mutations, Austria Lapari treatment significantly prolonged its progression-free survival (mPFS: 10.
7 months) [3]
.

In addition, the study confirmed that the genetic test results of paired tissue samples and plasma samples in mCRPC patients have a positive consistency as high as 91.
7% [3], while the positive consistency of tissue and plasma paired samples in the olaparib III registration clinical study PROfound It is 82% [4]; domestic and foreign data fully show that for mCRPC patients who cannot provide tissue samples or fail the test of tissue samples, genetic testing of plasma ctDNA samples is a reliable choice
.

This study included 39 mCRPC patients who spontaneously received olaparib monotherapy or combined with abiraterone between December 2017 and June 2021.
The tumor burden was high at the time of initial diagnosis, and 81.
8% of patients had bone metastases.
, 87.
2% of patients received new endocrine therapy, 61.
5% of patients received docetaxel chemotherapy
.

18 patients carried at least one disease-causing mutation in the HRR gene, and 21 patients were negative for HRR mutations; some of these negative patients carried Variant of Uncertain Significance (VUS) or other pathogenic mutations in DNA repair pathways due to lack of other treatments Options are available, and the patient agrees to receive olaparib treatment
.

The analysis found that 40% of the patients in the total population achieved PSA50 remission, and the median PSA progression-free survival time was 3.
1 months
.

50% of HRR-positive patients achieved PSA50 remission, and PSA progression-free survival was 5.
3 months; among them, patients with BRCA2 mutations benefited the most, with a median PSA progression-free survival of 9.
5 months
.

The PSA50 remission rate of people carrying HRR gene mutations in the PROfound study was 30% after receiving olaparib treatment [3], which shows that Chinese mCRPC patients can achieve similar or even better curative effects in real-world treatments
.

At the same time, PSA remission was also observed in 31.
1% of HRR mutation-negative patients.
The treatment-effective mutation-negative patients were mainly patients with HRR mutations of unknown significance and other pathogenic mutations in DNA repair pathway genes
.

Further analysis revealed that 3 clinically significant mutation sites were predicted to be harmful to protein function by computer SIFT software, and the 3 patients with these mutations all had longer PSA remission and PSA progression-free survival, suggesting the future need for mutations of unknown significance For a more in-depth genetic interpretation, patients with mutations of unknown significance may consider medication
.

In the analysis of the study, a number of long-lived patients with effective time of more than 1 year after receiving olaparib were observed, suggesting that even if receiving olaparib in the second-line mCRPC treatment, there can still be long-term benefits
.

A research report by Dr.
Dong from Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine shows that mCRPC patients in the real world in China can benefit from olaparib treatment, and the therapeutic efficacy is similar to phase III clinical trials; in addition, when carrying HRR mutations of unknown significance and other The therapeutic effect of olaparib has also been observed in people with gene mutations in the DNA repair pathway, suggesting that more in-depth genetic interpretation is needed for mutations of unknown significance, and medications can be considered according to the patient's condition
.

Expert profileProfessor Xue Wei, deputy dean of Renji Hospital, Shanghai Jiaotong University School of Medicine, Chief Physician, Professor, Ph.
D Supervisor, Shanghai Leading Talents Shanghai Craftsman, Shanghai Medical Craftsman Shanghai Excellent Academic Leaders, Shanghai Medical Leading Talents Chinese Medical Association Urology Standing Committee Member, Shanghai Medical Association Urology Branch Vice Chairman, Shanghai Urology Clinical Quality Control Center Chairman, China Healthcare International Exchange Promotion Association Endoscopy Endoscopy Branch Vice Chairman, Chinese Medical Doctor Association Urology Branch Member, Chinese Medical Association Deputy leader of the Minimally Invasive Group of the Urology Branch, "Chinese Journal of Urology", "Shanghai Medical Journal", "Shanghai Medical Journal", the visiting associate professor of MD Anderson Cancer Center, USA.
Introduction of research direction: Long-term clinical and basic research on prostate cancer, including stimulus in clinical practice The study of Mann spectroscopy in prostate cancer pathology imaging; PSMA-PET-CT, based on tissue gene detection and BCR after radical prostatectomy, recurrence and metastasis; neoadjuvant chemotherapy for locally advanced and oligometastatic prostate cancer research; metastasis Study on the efficacy of systemic treatment of prostate cancer with or without cryoablation focal treatment
.

Basic research focuses on the recurrence and metastasis of prostate cancer, and explores the role of key cell transduction pathways in tumor progression in the metabolism and immunity of tumor cells and microenvironment
.

He presided over 9 projects at various levels, including the National Natural Science Foundation of China, Shanghai Municipal Commission of Science and Technology, and Shanghai Shenkang Hospital Development Center, and published 51 papers, including 30 papers included in SCI, 11 papers with IF >5 points, and 3 books.
Declared 1 invention patent and participated in the compilation of 8 expert consensus on diagnosis and treatment of prostate cancer in China
.

Expert profile Dr.
Dong Baijun, deputy chief physician of the Department of Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Ph.
D.
, postdoctoral supervisor at the MD Anderson Cancer Center, USA Postdoctoral Fellow of the Prostate Cancer Expert Committee of the Chinese Society of Clinical Oncology Member of the Basic Research Group of the Urology Branch of the Chinese Medical Association Member of the Prostate Cancer Group of the Chinese Anti-Cancer Association Urinary Male Reproductive Tumor Committee Member of the Chinese Anti-Cancer Association Tumor Marker Committee Member of the Tumor Multidisciplinary Diagnosis Cooperation Group Member of the Chinese Anti-Cancer Association Tumor Interventional Ablation Expert Committee Member of the Chinese Journal of Urology The Secretary-General of the Editorial Board of "BJUI Chinese Edition" is mainly engaged in the clinical diagnosis, treatment and research of urinary tract tumors, especially prostate cancer.
He is good at accurate, painless, targeted puncture of prostate, and robot-assisted/laparoscopic radical treatment of prostate cancer.
surgery, prostate cancer cryoablation / High Intensity focused ultrasound / nano knives Supermicroinvasive surgery, molecular diagnosis of prostate cancer and precise diagnosis, individualized treatment of castration-resistant prostate cancer, neuroendocrine differentiation comprehensive diagnosis and treatment of prostate cancer and so on
.

As the person in charge, apply for 1 general project of the National Natural Science Foundation of China, 3 provincial and ministerial scientific research projects such as the Shanghai Municipal Science and Technology Commission, 1 project each from the Shanghai Municipal Health Commission and the Municipal Education Commission, and publish SCI-listed papers as the first or corresponding author 50 Articles
.

Participated in the compilation of the Guidelines for Diagnosis and Treatment of Chinese Urology and Andrology Diseases (2019 Edition) (Prostate Cancer, Science Press, 2020/10) and Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Prostate Cancer 2020 (People's Medical Publishing House, 2020/09) ), as well as 8 Chinese expert consensus on prostate cancer diagnosis and treatment, including the Chinese Expert Consensus on the Organization and Implementation of the Multidisciplinary Team for the Diagnosis and Treatment of Tumors of the Urinary and Male Reproductive System (2020 Edition)
.

Received the 2017 Shanghai Talent Development Fund, the 2019 Shanghai Education Commission’s High Altitude Discipline Construction Program Research Physician Fund, the Shanghai Medical Association Urology Branch "2019 Young Talents", 2020 China Cancer Prevention Annual Conference "People's Good Doctor (Urinary Medicine) Oncology) Golden Camellia·Outstanding Contribution" Title Reference: [1].
Abida, W.
, et al.
, Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.
JCO Precis Oncol , 2017.
2017.
[2].
Fan L, Fei X, Zhu Y, et al.
Comparative Analysis of Genomic Alterations across Castration Sensitive and Castration Resistant Prostate Cancer via Circulating Tumor DNA Sequencing.
J Urol.
2021;205(2): 461-469.
doi:10.
1097/JU.
0000000000001363[3].
Dong B, Fan L, Yang B, et al.
Use of Circulating Tumor DNA for the Clinical Management of Metastatic Castration-Resistant Prostate Cancer: A Multicenter, Real-World Study.
J Natl Compr Canc Netw.
14 2021:1-10.
doi:10.
6004/jnccn.
2020.
7663[4].
Kim Chi et al.
concordance of BRCA1,BRCA2 and ATM alterations identified in matched tumor tissue and circulating tumor DNA in men with metastatic castration-resistan t prostate cancer screened in the PROfound study.
2021 Annual Meeting of ASCO-GU abstract 26*This article is only used to provide scientific information to medical professionals , Does not represent the views of this platform