Guidelines·Evidence-based·Practice│Analysis of the first-line choice of new endocrine drugs for mCRPC treatment in multiple dimensions

Prostate cancer is a malignant tumor that seriously threatens men’s health, and its incidence in China is increasing year by year.

Most prostate cancer patients in my country have already metastasized when they are first diagnosed.

For patients with distant metastases, the 5-year relative survival rate of 80% of patients who have never metastasized dropped to 30%1.

Once the patient enters the stage of metastatic castration-resistant prostate cancer (mCRPC), the prognosis is relatively worse.

Therefore, patients with mCRPC have high demand for treatment and high cost of trial and error.

In recent years, more and more new endocrine therapy drugs have been approved for the treatment of mCRPC, such as abiraterone acetate as the first new endocrine drug to enter the Chinese market, bringing more treatment opportunities to Chinese patients .

How to choose first-line treatment drugs to maximize the survival benefits of patients has become a key challenge for clinicians.

Compliance with guidelines: The recommended clinical guidelines for the first-line treatment of mCRPC from authoritative guidelines at home and abroad are an important basis for making treatment decisions.

The therapeutic value of abiraterone acetate in mCRPC has been confirmed by a series of classic studies, and it has been recognized and unanimously recommended by authoritative guidelines at home and abroad.

The 2020 CSCO Guidelines for the Diagnosis and Treatment of Prostate Cancer 2 recommends abiraterone acetate for the first-line treatment of mCRPC patients (level I recommendation; 1A evidence) (Figure 1).

Figure 1 2020 CSCO prostate cancer diagnosis and treatment guidelines recommend the 2020 American Urological Association Educational Association (AUA) in conjunction with the American Society of Radiation Oncology (ASTRO) and the Society of Urinary Oncology (SUO) to develop advanced prostate cancer guidelines 3 recommend abiraterone acetate as First-line treatment for mCRPC (strong recommendation; level of evidence: A) (Figure 2).

Figure 2 2020 AUA/ASTRO/SUO Advanced Prostate Cancer Guidelines recommends the 2020 jointly issued by the European Society of Urology (EAU), European Society of Radiation Oncology (ESTRO), European Society of Urogenital Radiology (ESUR) and International Society of Geriatric Oncology (SIOG) The version 4 of the prostate cancer guidelines also recommends abiraterone acetate as the first-line treatment for mCRPC (Figure 3).

Figure 3 The 2020 EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guidelines recommend evidence-based: survival benefits and quality of life, which evidence-based medicine has strong evidence? In the mCRPC stage, due to the increase of metastases, the androgen is too high, and it may not reach the castration of the local lesions.

Abiraterone acetate is a highly selective CYP17 enzyme inhibitor, which can block androgens from all sources, no matter for systemic or local purpose, and bring better benefits.

A Canadian randomized controlled clinical study5 explored the best sequence of abiraterone acetate and enzalutamide in the treatment of mCRPC patients.

Patients were randomly assigned to abiraterone acetate (1000 mg orally, once a day) + prednisone (5 mg orally, twice a day) at a ratio of 1:1 until PSA progressed, and then switched to enzalutamide (160 mg orally).
mg orally, once a day) (group A) or the reverse order (group B).

The results showed that the first-line use of abiraterone acetate significantly prolonged the second PSA progression time (19.
3 months vs 15.
2 months; HR 0.
66; P=0.
036) in patients with the second PSA progression compared to the first-line use of enzalutamide, and PSA responders were more in the second-line treatment.
More (36% vs 4%) (Figure 4).

Figure 4 The second PSA progression time (A) and PSA response (randomized controlled study) after first-line treatment.
The median overall survival (OS) of first-line abiraterone acetate showed a prolonged trend by 4.
1 months (28.
8 months) vs 24.
7 months).

In general, first-line abiraterone acetate provides more treatment possibilities and gains valuable time for mCRPC patients.

Figure 5 OS of first-line abiraterone acetate or first-line enzalutamide (randomized controlled study) In another retrospective study comparing abiraterone acetate and enzalutamide for the treatment sequence of mCRPC patients, the first-line acetic acid was used Compared with the first-line use of enzalutamide, abiraterone significantly prolonged the progression-free survival of patients (median PFS: 19.
53 months vs 13.
02 months), and the risk of disease progression was reduced by 63% (HR 0.
37) (Figure 6).

Figure 6 PFS (retrospective analysis) quality of life of first-line abiraterone acetate or first-line enzalutamide, a retrospective study 7 evaluated first-line abiraterone acetate, enzalutamide, bicalutamide or chemotherapy The incidence of central nervous system (CNS) events in patients with advanced prostate cancer.

The results showed that the first-line use of abiraterone acetate significantly reduced the risk of CNS events by 20% compared with the first-line use of enzalutamide (P = 0.
0388).

A phase IV, prospective, open, multicenter, real-world study (REAAcT)8 compared the tolerance of mCRPC patients receiving enzalutamide or abiraterone acetate plus prednisone.

The results showed that compared with enzalutamide, abiraterone acetate + prednisone treatment had a lower incidence of overall adverse events, fatigue, and clinically significant cognitive decline (Figure 7).

Another prospective observational study (AQUARiUS)9 also showed that in the real world, compared with enzalutamide, abiraterone acetate + prednisone has advantages in fatigue and cognitive function.

This discovery occurred early after the start of treatment, based on the fact that the patient population is mostly elderly men, so the clinical choice of treatment should consider the impact of this difference on patients.

Figure 7 The clinically significant difference between abiraterone acetate + prednisone and enzalutamide in the treatment of mCRPC patients.
Re-practice: 5 years of clinical use experience and adequate medication practice data.
Since abiraterone acetate was approved in China in 2015, its actions A new type of endocrine drug has become one of the effective treatments for mCRPC.

Abiraterone acetate has been used clinically in China for 5 years.
It has benefited a large number of prostate cancer patients, and has accumulated sufficient experience in efficacy and safety.
It is a therapeutic drug trusted by doctors and patients. The first-line use of abiraterone acetate has definite efficacy and safety, and may bring maximum clinical benefit to patients with mCRPC.

Expert comments: Professor Ye Dingwei • Chief Physician, Doctoral Supervisor • Associate Dean of Fudan University Cancer Hospital • Leader of Urology Department • Chief Expert of Urological Oncology MDT • Director of Shanghai Urological Oncology Institute • Director of Prostate Cancer Institute of Fudan University •Chairman of the Chinese Anti-Cancer Association Urinary Male Reproductive Cancer Committee •Chairman of the Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Committee •Vice Chairman of CSCO Urothelial Cancer Committee •Vice of CSCO Kidney Cancer Committee Chairman • Vice Chairman of CSCO Immunotherapy Special Committee • Chairman of the Urinary Oncology Cooperative Group (UCOG) of China Cancer Hospital • Executive Director of the Chinese Anti-Cancer Association • Executive Director of CSCO Professor Ye Dingwei: mCRPC is the terminal stage of prostate cancer.
The prognosis is poor, and improving the patient's survival benefit and quality of life is the goal of treatment.

From the perspective of randomized controlled studies and real-world studies, the first-line use of abiraterone acetate in mCRPC patients has more prominent performance in improving survival and maintaining quality of life, and has brought significant benefits to patients.

For the multi-line treatment options for mCRPC patients, more clinical studies will be carried out in the future to observe and determine.

It is believed that with the continuous progress of research in the field of mCRPC and the continuous optimization of treatment plans, the survival benefits of patients will be further improved.

Professor Zhou Fangjian • Chief Physician and Doctoral Supervisor • Director of Department of Urology, Sun Yat-sen University Tumor Hospital • Chief Expert of Prostate Cancer Single Disease, Sun Yat-sen University Tumor Hospital • China Anti-Cancer Association Urogenital Tumor Specialized Committee 1st and 2nd Deputy Director Committee • The second council member of the Chinese Society of Clinical Oncology (CSCO) • Vice Chairman of the CSCO Prostate Cancer Expert Committee • Vice Chairman of the CSCO Bladder Cancer Expert Committee • Director of the South China Da Vinci Surgical Robot Technology Training Center • Guangdong Anticancer Association Urinary and Reproductive Director of the Department of Oncology Committee • Deputy Chairman of the Ninth Committee of Urology Branch of Guangdong Medical Association • Member of Urology Branch of Chinese Medical Association • Editorial Board of Chinese Journal of Urology • Standing Editor of Chinese Journal of Cancer Professor Zhou Fangjian: For mCRPC patients , Timely diagnosis and taking measures are the prerequisites for survival and benefit.

With the continuous update and progress of drug therapy, patients with mCRPC have more and more treatment options.

The new endocrine treatment program represented by abiraterone acetate has excellent efficacy and safety, and is favored by clinicians and patients.

The results of two large studies COU-AA-301/COU-AA-302 confirm that abiraterone acetate can significantly improve the survival benefit of mCRPC patients regardless of whether they have received docetaxel chemotherapy in the past.

In the COU-AA-302 study, the OS of non-chemotherapy patients who received the abiraterone acetate regimen was 34.
7 months; the patients with milder symptoms who had not been treated with abiraterone acetate benefited more from abiraterone acetate treatment, and the OS was as high as 53.
6 months.
Patients with mCRPC should start abiraterone acetate treatment as soon as possible.

Focusing on precision medicine research, paying attention to real-world research, and emphasizing the difference between China and the West, is expected to benefit Chinese patients more.

References: 1.
The Professional Committee of Urinary Male Reproductive Tumors of the Chinese Anti-Cancer Association.
The 2018 Chinese Expert Consensus on the Diagnosis and Treatment of Metastatic Prostate Cancer.
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The Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Prostate Cancer 2020, Chinese Society of Clinical Oncology Guidelines Working Committee , 2020.
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ADVANCED PROSTATE CANCER:AUA/ASTRO/SUO GUIDELINE 2020.
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EAU-EANM -ESTRO-ESUR – SIOG.
Guidelines on Prostate Cancer.
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Khalaf DJ, et al.
Lancet Oncol, 2019; 20: 1730-39.
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