Professor Fan Xinrong: NHT is booming, mHSPC combination therapy is charging again

"An "Medicine" Happy Industry" is a humanistic case collection project
cooperated by Beijing Chen Jumei Public Welfare Foundation and Yimaitong.

The series of interviews with urology doctors will focus on the field of prostate cancer, discuss the significance of standardized diagnosis and treatment paths and whole-course management of prostate cancer to clinical patients based on the real clinical needs, and highlight the research spirit and professionalism of urological oncologists
.

Looking back, the standard treatment for metastatic hormone-sensitive prostate cancer (mHSPC) was based on androgen deprivation therapy (ADT) alone for a long time, and although the patient's condition could be controlled and relieved, almost all mHSPC patients receiving ADT would eventually progress to castration-resistant prostate cancer (CRPC), which was more life-threatening
.

With the development of new endocrine therapy (NHT), the study found that ADT combined with chemotherapy drugs and NHT drugs can further extend the survival time of mHSPC patients and improve patient survival, and mHSPC gradually enters the era of
combination therapy.

In this issue, we have the honor to invite Professor Fan Xinrong of Peking Union Medical College Hospital to share the development process of mHSPC treatment options, as well as the changes and new challenges
brought by the rise of NHT to mHSPC clinical decision-making.

Expert profile

Professor Fan Xinrong

Chief Physician Master Supervisor Doctor of Medicine

He graduated from the Department of Clinical Medicine of Peking Union Medical College in 1997 and worked in Peking Union Medical College Hospital after graduation

He specializes in the comprehensive treatment of various tumors in the urinary system

He is a member of the International Exchange Committee of the Urology Branch of the Chinese Medical Association

Member of the Expert Committee on Urothelial Cancer of the Chinese Society of Clinical Oncology

Vice Chairman of the Urological Tumor Branch Committee of Beijing Cancer Prevention and Treatment Research Association

Member of the Urinary Oncology Group of the Oncology Branch of the Beijing Medical Association

Member of the Standing Committee of the Multidisciplinary Diagnosis and Treatment Committee of Beijing Medical Awards Foundation

He is a member of the Beijing Medical Doctor Association

Member of the European Society of Urology

Academic Advisor to Uptodate

From simple castration to diverse combinations, NHT has helped make new breakthroughs in mHSPC triple therapy

In China, despite the rapid development of medical standards, the proportion of mHSPC patients in the first diagnosis of prostate cancer is as high as 54%, which is much higher than that of European and American populations
.

In this regard, Professor Fan Xinrong said that the public's awareness and attention to the disease of prostate cancer is still insufficient, and it is imperative to strengthen the early screening and prevention of prostate cancer
.

Prostate cancer is androgen-dependent
.

Professor Fan Xinrong said that in previous clinical practice, castration therapy has always been the most important treatment method
for mHSPC patients.

Drug castration, also known as ADT therapy, that is, by inhibiting testosterone secretion to reduce the level of androgen in the patient's body, so as to achieve the purpose of inhibiting tumor growth, traditional ADT drugs include leuprolidene, triprelin, goserelin and the like
.

Although ADT alone has a good effect on alleviating patient pain, unfortunately, this treatment regimen does not significantly prolong patient survival
.

With the update of drug research and the advancement of medical standards, mHSPC treatment has entered the era of combination therapy from the era of pure ADT treatment
.

Professor Fan Xinrong said that as early as 2015, CHAARTED, STAMPEDE and other trials found that compared with ADT treatment alone, the chemotherapy drug docetaxel combined with ADT treatment can significantly improve the overall prognosis of patients with high tumor load and prolong the survival of
mHSPC patients.

Since then, chemotherapy combined with ADT, a new treatment regimen, has entered the clinic, and has achieved higher survival benefits for patients with high tumor load mHSPC
.

In addition to the combination with chemotherapy, ADT and NHT-related research have also achieved fruitful results
.

NHT drugs such as enzalumine, apatamide, and abiraterone have been shown to significantly prolong the survival time of mHSPC patients, and the combination of ADT+NHT has become a powerful weapon
in the clinical treatment of mHSPC.

With the continuous in-depth exploration of drug combination therapy, the triple trial of ADT+NHT dual therapy in combination with chemotherapy has also achieved positive results
.

The results of ARASENS and PEACE-1 trials showed that ADT+docetaxel + NHT drug triplet therapy could further prolong patient survival and delay the entry of
mHSPC patients into CRPC compared with ADT combined with docetaxel.

Based on the latest research results, the 2022 new CSCO prostate cancer diagnosis and treatment guidelines officially incorporated the "ADT+NHT+chemotherapy" triple therapy into the mHSPC treatment system, once again optimized the mHSPC combination treatment plan, and opened up a new era of triple therapy for prostate cancer patients
.

NHT drugs are in full bloom, and multiple mechanisms are heroic

Professor Fan Xinrong said that before the NHT drug was born, prostate cancer patients treated with ADT or ADT combined with a generation of androgen receptor blockers entered the CRPC for an average of only about one and a half years from mHSPC to CRPC, and with the application of NHT drugs, mHSPC patients entered CRPC for a significant time, almost reaching more than 3 years, and the survival benefit of patients was greatly improved
.

Talking about the bright performance of NHT drugs, Professor Fan Xinrong pointed out that prostate cancer is driven by androgens, and ADT drugs alone can only block the production of testicular derived androgens, can not inhibit the secretion of androgens and their derivatives derived from the pituitary-adrenal axis, nor can they block the production of androgens derived from prostate tumor cells, so the therapeutic effect is limited
.

NHT drugs are able to block androgen production from multiple sources to a greater extent through multiple mechanisms of action
.

For example, abiraterone acetate is an CYP17 enzyme inhibitor that inhibits androgenic extracorporeal synthesis of adrenal and tumor cells; Enzalumine and apatamine are both potent new androgen receptor (AR) blockers, with a triple action mechanism, which can not only block androgen binding to AR, but also affect AR and DNA binding by inhibiting AR cell nuclear shift, nucleic acid attachment and transcription, preventing gene expression and inhibiting tumor cell growth
.

mHSPC treatment strategies are frequently new, and individualized diagnosis and treatment are re-explored

Based on the concept of prostate cancer management and precise treatment, the individualized treatment plan for mHSPC patients has become a new direction
for prostate cancer clinicians.

Professor Fan Xinrong said that according to the guidelines, the clinical use of abiraterone combined with ADT or chemotherapy combined with ADT for patients with high metastatic load is more likely to ensure the therapeutic effect of patients with endocrine diseases such as diabetes, and the use of androgen receptor blockers such as enzalumine or apatamide with less impact on the endocrine system can better ensure the therapeutic effect of patients; Radiation therapy is generally not used in patients with high metastatic load, but if the patient is oligometastatic, the treatment of limited lesions by local measures such as surgery and radiotherapy may maximize the survival benefit
.

For the development direction of accurate diagnosis and treatment of prostate cancer, Professor Fan Xinrong said that under the current framework of prostate cancer diagnosis and treatment, a more detailed division of patients is conducive to the formulation of individualized clinical decisions; In the context of the emergence of treatment strategies, the early formulation of unified standards for the selection and application of combination treatment options for prostate cancer is also an important research content
to promote the precise treatment of prostate cancer.

Expert thoughts

Professor Fan Xinrong said that the emergence of NHT drugs has made mHSPC treatment break through the simple castration treatment mode, showing a glorious scene of hundreds of boats competing for the current and thousands of sails, which not only strengthens the life barrier for patients, but also delivers greater hope
for the clinical medicine of prostate cancer.

Past Review

1.
Professor Zhu Yao: The revision of the guidelines is like building a giant ship, carrying the hopes of patients all the way forward

2.
Easy to find Professor | The "growth" of the guide accompanies the breakthrough of diagnosis and treatment, and guides the future to a brighter and smoother road

3.
Professor He Weiyang: The development of anti-androgenic drugs: a clinical "revolution" driven by drug resistance

4.
Director Li Rubing: White clothes, clever hands, red heart - prostate cancer diagnosis and treatment concept and medical spirit

5.
Professor Ma Limin: "Medicine" has a long way to go, and the waves are gushing

6.
Professor Sun Ting: Optimization strategy for the whole process of prostate cancer management from one end to the end

7.
Professor Wang Jianbo: Literature and martial arts are both complete, hundreds of steel, doctors have a long way to go

Special thanks to: Beijing Astellas Pharmaceutical Co.
, Ltd

Editor: Weimong

Review: Bingxin

Typesetting: LR