Secret legend, Dengxinjing Prostate Cancer Summit Forum was grandly held, took stock of progress in the field, and gathered the essence of big coffee

*For medical professionals to read and refer to the 2022 AstraZeneca Prostate Cancer Summit Highlights Review
.

On February 26, 2022, the AstraZeneca Prostate Cancer Summit Forum was grandly held
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With the theme of "Legend of Secretion, Entering the New Realm", the forum reviewed the development of prostate cancer and looked forward to the new future of urology
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At this forum, experts in the field of prostate cancer from all over the country gathered online and offline to take stock of the progress in the field, analyze the development trend, express their insights, and share an academic feast
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Online experts and offline sub-venues, Professor Huang Jian of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Academician Zhang Xu of Chinese People's Liberation Army General Hospital, and Professor Wei Qiang of West China Hospital of Sichuan University made wonderful opening speeches, which kicked off the summit forum
.

Prof.
Huang Jian, Academician Zhang Xu and Prof.
Wei Qiang gave opening remarks.
Ms.
Xie Qiong, Vice President of AstraZeneca China Oncology Urology/Gynecology/Female Oncology, delivered a welcome speech.
In her speech, she said that AstraZeneca has been deeply engaged in the field of prostate cancer treatment.
For many years, in addition to the classic internal therapy drugs goserelin and bicalutamide, liparib for prostate cancer was also launched in June last year, which promoted the development of mCRPC precision therapy and further helped Chinese urologists.
benefit more patients
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Vice President Xie Qiong delivered a welcome speech The new standard of prostate cancer diagnosis and treatment: early diagnosis and early screening + innovative technology.
At the beginning of the conference, Professor Huang Jian shared the theme of "Looking Back at the Footprints of the Prostate Cancer, and Working Together to Explore the New Realm"
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Prostate cancer has become a male malignancy with the fastest growing incidence and a sustained and rapid increase in mortality in China in the past decade, seriously threatening the health of men in China
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Professor Huang Jian reviewed the new progress in the diagnosis and treatment of prostate cancer in recent years, bringing more choices to the clinic from screening, diagnosis and treatment
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Later, Professor Huang Jian also looked forward to the future direction of prostate cancer diagnosis and treatment at the forum: he hoped to continue to promote the early screening and diagnosis of prostate cancer, and insist on developing various innovative technologies; he hoped to explore a prostate cancer screening mode that conforms to Chinese characteristics from practice.
, Prostate cancer diagnostic markers suitable for the ethnic characteristics of the Chinese population; popularize MRI-guided targeted/combined puncture, and use emerging technologies to further improve the positive rate of puncture; explore more accurate prostate cancer diagnostic techniques and optimize the prostate cancer pathology system; he believes that Various new treatment methods such as molecular targeting, immunotherapy and gene therapy can be expected in the future; it is hoped that standard diagnosis and treatment norms will be further formed to create the whole course management of prostate cancer
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Classic Continuation: Endocrine Therapy for Prostate Cancer Over Time ▌ Prostate Cancer Drug Therapy: The journey is long, only the struggle Academician Zhang Xu Academician Zhang Xu launched a keynote report on "The Long Journey: The Future of Prostate Cancer Drug Therapy"
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With the advancement of new endocrine therapy, only new endocrine therapy drugs (NHA) or chemotherapy can no longer meet the clinical treatment needs of metastatic castration-resistant prostate cancer (mCRPC)
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Prostate cancer drug treatment has shifted from point-to-point attack to point-to-point attack, and precise targeted therapy has become the development direction of mCRPC treatment
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In recent years, the US Food and Drug Administration (FDA) has approved some new treatments including PARP inhibitors (such as olaparib), radioligand therapy and cabazitaxel
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In addition, a large number of mCRPC signaling pathway drugs are currently under development
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For example, the protein degradation targeting chimera (PROTAC) drug ARV-110 has shown a certain anti-tumor effect in phase I and II studies, and is currently conducting a phase III study
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Prostate-specific membrane antigen (PSMA) is a cell-surface transmembrane glycoprotease that is highly overexpressed in CRPC
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In 2020, the VISION study confirmed the survival benefit of Lu177-PSMA in patients with advanced mCRPC
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A Phase III study of PSMA in the early stages of metastatic prostate cancer is currently underway
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In addition, PSMA-targeted antibody-drug conjugates (ADC), PSMA-targeted CAR-T cell therapy, and PSMA-targeted bispecific T cell redirection therapy are also being explored
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▌ AstraZeneca's R&D in the field of urology: the road is long and the medical road is accompanied by Dr.
He Jing, AstraZeneca's senior vice president of global oncology research and development, and the president of the global R&D China center, Dr.
He Jing launched "The medical road is accompanied by: AstraZeneca's research and development process in the field of urology.
and Outlook" theme report
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In the report, Dr.
He Jing reviewed and looked forward to AstraZeneca's research and development process in the field of urological oncology.
AstraZeneca will comprehensively develop drugs in the fields of bladder cancer, kidney cancer and prostate cancer to benefit patients
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The PROfound study of olaparib in prostate cancer found that olaparib prolonged median imaging progression-free survival (mrPFS) and median survival, respectively, in BRCA1/2 or ATM-mutated NHA-treated mCRPC populations (mOS) was about 4 months and 4.
4 months, and in the PROpel study, it was found that olaparib combined with abiraterone significantly prolonged the rPFS of the first-line full population mCRPC patients compared with abiraterone alone, reaching 24.
8 months.
The median rPFS of patients treated with the combination was more than two years, and the benefit was independent of HRR mutation status
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Important research is underway on the new drug Capivasertib, so stay tuned
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Since 1996, AstraZeneca has gone through 26 years in the field of prostate cancer treatment, and will continue to develop and innovate in the future
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▌ Selection of LHRH agonists: good efficacy, high safety, and economic convenience Prof.
Dingwei Ye from Fudan University Affiliated Cancer Hospital's theme report "Insights: Application and Exploration of LHRH Agonists in Chinese Prostate Cancer Patients" clearly pointed out: 2021 The Chinese version of the guidelines for the diagnosis and treatment of prostate cancer, the 2021 version of the European Association of Urology (EAU) guidelines, the National Comprehensive Cancer Network (NCCN) guidelines and other domestic and foreign guidelines are recommended, goserelin as the representative of castration therapy throughout the whole process of prostate cancer treatment; Compared with goserelin, leuprolide has a castration escape rate as high as 10%, and a higher proportion of patients with testosterone levels reduced to 20ng/dL after use of goserelin, and reduced prostate-specific antigen (PSA) levels Better; Goserelin not only has more than 10 years of long-term efficacy and safety follow-up data, but also the long-acting dosage form once every three months is more in line with the follow-up frequency in the post-epidemic era, which can reduce the number of injections and doctor visits, and reduce patient delays in injections proportion
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In addition, after goserelin entered the national medical insurance negotiation catalogue in 2021, it has become the LHRH agonist with the lowest price
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International and domestic survey data show that an ideal LHRH agonist needs to meet the demands of clinicians, nurses, pharmacists and patients
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Goserelin has become the LHRH agonist with the highest comprehensive score due to its superior efficacy, safety, long-acting dosage form, improved treatment compliance, high convenience, low acupuncture injury rate and high cost performance
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▌ The advantages of long-acting dosage forms are fully demonstrated: see the world on the shoulders of giants.
In order to improve the survival of patients, the treatment plan for prostate cancer has been continuously developed
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Professor Zhang Jian from Xinhua Hospital Affiliated to Shanghai Jiaotong University Hospital brought a keynote report on "Classic Remodeling: Application and Pharmacy Value of Long-acting Formulations in Endocrine Therapy of Prostate Cancer"
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It pointed out that even though new drugs for the treatment of prostate cancer emerge in an endless stream, endocrine therapy based on "castration" runs through the whole process of prostate cancer treatment, and LHRH agonists represented by goserelin still occupy the cornerstone of endocrine therapy.

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Compared with natural LHRH, LHRH agonists have stronger activity and stronger binding ability to receptors, among which only goserelin binds to GnRH receptors 100 times stronger than natural GnRH
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Both domestic and foreign guidelines recommend long-acting formulations of LHRH agonists for the treatment of prostate cancer
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As a representative drug of LHRH agonist, goserelin has multiple advantages: compared with microsphere injection, goserelin adopts sustained-release implant, which can release enough and stably to ensure the curative effect; it adopts safe needle design, and the use experience is good; Effectively improve testosterone and PSA levels
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Roundtable Discussion 1: Long-acting dosage forms become a common treatment method in the post-epidemic era.
Professor, Professor Wang Shaogang of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, and Professor Xu Chuanliang of the First Affiliated Hospital of Naval Military Medical University, focusing on "Impressions and future prospects for the development and changes of prostate cancer diagnosis and treatment in the past", "The direction or target of future prostate cancer drug research and development" The advantages of long-acting dosage forms” and other topics
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All experts agreed that: in recent years, the diagnosis and treatment of prostate cancer in China has developed rapidly, and some aspects have been at the forefront of the world, but there are still many problems to be explored
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For example, with the application of precise imaging methods such as PSMA PET/CT, whether biochemical recurrence and non-metastatic castration-resistant prostate cancer (nmCRPC) need to be redefined after radical resection
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New drugs for prostate cancer emerge in an endless stream, and potential R&D directions and targets include PARP inhibitors, PROTAC, PSMA targeted therapy, AKT inhibitors,
etc.

The efficacy of long-acting dosage forms represented by goserelin is consistent with that of short-acting dosage forms, and both have good effects in reducing testosterone and PSA
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Goserelin is injected once every three months, which is more convenient; the proportion of delayed injections is lower, which helps patients maintain testosterone and PSA levels more stably
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In the epidemic and post-epidemic era, the use of long-acting dosage forms can help reduce the number of patients visiting the hospital and avoid cross-infection, which is in line with the national long-term prescription policy
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Moreover, after goserelin enters the 2021 national medical insurance negotiation catalog, it is currently the most cost-effective LHRH agonist
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Focus on precise diagnosis and treatment: mCRPC targeted therapy brings new hope for long-term survival "Precise Choice" theme report
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Olaparib is currently the only PARP inhibitor approved in China for the treatment of patients with BRCA-mutated mCRPC who have progressed on NHA therapy
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PROfound is the first large-scale phase III clinical study to guide precise targeted therapy with molecular typing in prostate cancer and achieve positive results
.

The results of the study showed that, compared with the NHA sequential treatment group, olaparib monotherapy could increase the rPFS of BRCA-mutated mCRPC patients to 9.
8 months, which was more than 3 times that of the control group; OS was more than 20 months, compared with the control group.
The group was extended for about half a year, reducing the risk of disease imaging progression by 78% and the risk of all-cause mortality by 37%; reducing the risk of pain progression, and the benefit was more pronounced in the chemotherapy-naive patient population
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In addition, the real-world study of Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine showed that Chinese mCRPC patients had a good response rate to olaparib; the real-world study of Fudan University Cancer Hospital showed that olaparib was effective in mCRPC patients, and Safe and controllable
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Currently, domestic and foreign authoritative guidelines all recommend category 1/strong olapa for patients with mCRPC who have progressed on previous NHA therapy and carry BRCA mutations
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▌ PARP inhibitor combined with NHA: Entering the first-line treatment of mCRPC in the whole population Prof.
Xin Gou, the First Affiliated Hospital of Chongqing Medical University, shared "Double Swords: The Latest Research Progress of ASCO GU in 2022"
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At the just-concluded 2022 ASCO GU Annual Meeting, PROpel Research released the latest data
.

Olaparib combined with abiraterone significantly prolonged rPFS in the overall first-line mCRPC population compared with abiraterone alone (24.
8 months vs 16.
6 months, HR 0.
66; 95%CI 0.
54-0.
81), and the median of patients receiving combination therapy For patients with rPFS greater than two years, the benefit of combination therapy was independent of HRR mutation status
.

The safety profile of the combination therapy was consistent with that of the two monotherapy, and most patients continued therapy until progression
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The PROpel study is the first randomized controlled phase III clinical study to achieve positive results in the whole first-line population of mCRPC, indicating that the first-line treatment of mCRPC is about to usher in important changes
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▌ Safe and controllable, long-term use of olaparib helps patients to benefit more Professor Lin Tianxin, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Reaction profile, common adverse reaction treatment principles and medication management
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From the research data and mechanism of action, the overall safety of olaparib is controllable and manageable, and it is a relatively safe PARP inhibitor.
Most adverse reactions can be effectively managed through supportive care
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The overall and grade 3 or higher adverse event rates were comparable to those of novel endocrine therapy with monotherapy, and most patients continued therapy until disease progression when used in combination therapy
.

Adverse reactions of different systems can be handled according to the severity classification and standardized procedures.
The first 6 months of treatment are the high-incidence stage of adverse reactions, which requires close monitoring
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In terms of medication management, clinicians should standardize the starting dose and discontinuation timing of olaparib to maximize patient benefit
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Olaparib is a concentration-dependent drug, which can exert anti-tumor activity only when it reaches an effective concentration, and its pharmacokinetics are similar in Eastern and Western populations, so it should be administered in accordance with the standard starting dose without additional dose adjustment
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The timing of discontinuation should also be carefully assessed, based on pre-specified treatment goals (eg, quality of life, patient-reported outcomes, or survival), with "no longer clinical benefit" as an indication
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In addition, efficacy evaluation and protocol adjustment should comprehensively evaluate clinical efficacy, biochemical indicators and imaging evidence
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▌ Accurate Detection and Guidance of Precise Medicine Prof.
Jiang Haowen from Huashan Hospital Affiliated to Fudan University, gave a keynote report on "Strive to Govern: The Road to Improvement in Genetic Testing of Chinese mCRPC Patients"
.

Genetic testing is the premise of precision treatment of prostate cancer.
The NCCN guidelines recommend that all metastatic prostate cancer patients undergo HRR gene testing as soon as possible from 2020, so as to guide precision medicine, especially patients with BRCA mutations can benefit from olaparib treatment.
benefit
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Moreover, the results of the research on gene mutation of prostate cancer in Renji Hospital show that the frequency of BRCA2 mutation in China is about 13% (germline + lineage)
.

Another study showed that the overall germline HRR gene mutation rate in China is similar to that in the West, and the germline BRCA1/2 mutation rate is about 7%
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In the selection of samples for testing, the success rate of ctDNA detection in mCRPC patients is high, and the consistency with the results of tissue testing is good, so it can be used as a sample selection for genetic testing
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Roundtable Discussion 2: Precision diagnosis and treatment help mCRPC patients to benefit more.
They expressed their opinions on topics such as the choice of treatment options for the whole first-line population of mCRPC without NHA treatment, "how to effectively manage drugs during olaparib treatment", "the significance of genetic testing in prostate cancer patients and the most appropriate time for HRR testing"
.

After heated discussions, all experts agreed that there is cross-resistance among NHA drugs, and sequential therapy is not effective
.

Olaparib is currently the only PARP inhibitor approved for the treatment of prostate cancer in China, providing a new treatment option for mCRPC patients who have progressed in NHA treatment and carry BRCA mutations
.

PROpel is the first phase III clinical study to explore the efficacy and safety of the combination of olaparib and abiraterone for 1L treatment in patients with mCRPC, and to report positive results in the entire population
.

The combination regimen of olaparib and abiraterone heralds an important change in the first-line treatment of mCRPC
.

In general, the safety of olaparib is controllable and manageable, and the earlier the use of patients, the more benefit
.

Elevated PSA alone is not sufficient to meet the criteria for disease progression
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In combination with EAU guidelines and CSCO guidelines, at least two of the three criteria (PSA progression, imaging progression, and clinical deterioration) should be met when evaluating mCRPC disease progression and discontinuation timing
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Olaparib is a concentration-dependent drug and must reach an effective concentration to exert antitumor activity
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Conference Summary Prof.
Ye Zhangqun from Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology gave a summary of the conference.
He pointed out: "This conference brings together top experts in the field of prostate cancer, from prostate cancer diagnosis to treatment, from frontier to clinical experience sharing.
, from the special report to the round table discussion, the content is splendid, bringing you an academic feast
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I hope that after returning to the clinical position, all colleagues will be able to apply the consensus reached in this meeting to clinical diagnosis and treatment, so as to provide patients with better care.
Bring more benefits
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" *This article is only for providing scientific information to medical professionals and does not represent the views of this platform