Case sharing takes a turn for the better, moving forward: the original research abiraterone brings lasting PSA reduction and disease control to patients

Prostate cancer is a typical heterogeneous tumor.
Due to the insidious disease and the lack of universal clinical screening, the proportion of patients with high-risk advanced prostate cancer and metastatic prostate cancer is relatively high
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Among them, metastatic hormone-sensitive prostate cancer (mHSPC) is a type of metastatic prostate cancer with a better prognosis, but patients at this stage will become metastatic castration-resistant prostate cancer (mCRPC), and the prognosis of patients is poor.

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At present, many authoritative guides at home and abroad recommend Zeke® (Abiraterone Acetate Tablets) for the first-line treatment of mHSPC and mCRPC
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This time, I will bring you 2 cases from the real world to share for readers to communicate and discuss
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Case 1 is a 78-year-old male patient with a medical history.
The chief complaint: prostate-specific antigen (PSA) has been elevated for more than 3 years
.

History of present illness: The patient's PSA was found to be elevated at about 4.
7 ng/ml during physical examination more than 3 years ago, and then slowly increased, without paying attention
.

In June 2017, another physical examination showed that PSA was 28.
6ng/ml.
The 12 needles of prostate puncture in the outside hospital showed that it was prostate acinar adenocarcinoma, with a Gleason score of 4+4
.

SPECT/CT indicated whole body bone metastasis (waist 2, waist 5 suspicious)
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The patient has long-term poor urination and increased nocturia (2-3 times)
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Digital rectal examination: The prostate is enlarged, and the surface of the double lobe touches many raised nodules with hard texture, which is closely related to the rectum
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Auxiliary blood test: hemoglobin (Hb) 126g/L, white blood cell count (WBC) 4.
7 x 10^9/L, platelet count (PLT) 132x10^9/L
.

CT: Changes in the lymph nodes adjacent to the iliac vessels
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Bone scan: Waist 2 shifted to waist 5 suspicious
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Figure The changes in the lymph nodes adjacent to the iliac vessels.
The diagnosis of whole body bone imaging results in high-risk mHSPC (T3N1M1b, Gleason score 4+4=8 points)
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Treatment After 5 months of endocrine therapy in a foreign hospital in May 2017, the patient went to our hospital
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In November 2017, the patient's PSA dropped to 5.
7ng/ml in June of endocrine therapy, and the original research abiraterone 1000mg combined with prednisone 5mg Qd was added, and the PSA improved significantly.
By April 2020, the PSA dropped to 1.
714ng/ml
.

In July 2020, the PSA rose to 2.
765ng/ml, and the prednisone was replaced with dexamethasone
.

In April 2021, the PSA was 1.
667ng/ml, and the domestic abiraterone was replaced at the end of the month
.

In July 2021, PSA rose to 2.
65ng/ml
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In August 2021, the PSA was 2.
635ng/ml, which was replaced by the original research abiraterone
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Case analysis: This patient is a high-risk mHSPC patient.
After endocrine therapy, the original abiraterone was added, and the PSA improved significantly
.

Authoritative guides at home and abroad recommend that abiraterone acetate is the first-line treatment plan for mHSPC patients 2-4
.

The LATITUDE study compared the results of the original research abiraterone combined with prednisone (AAP) + androgen deprivation therapy (ADT) vs.
ADT alone in the treatment of high-risk mHSPC patients.
The data showed that ADT+AAP significantly prolonged the median rPFS of high-risk mHSPC patients to 33 The analysis of different subgroups showed that ADT+AAP had consistent progression-free survival (PFS) benefits for high-risk mHSPC patients in different subgroups, and the risk of tumor metastasis progression in Asian patients was reduced by nearly 70%
.

The time to PSA progression in the original research abiraterone group was 33.
2 months, and the control group was 7.
4 months, reducing the risk of PSA progression by 70%
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Overall survival (OS) data showed that the median OS in the placebo group was 36.
5 months
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The original abiraterone group was 53.
3 months old, and the P value was significantly different5
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Figure LATITUDE study results The patient’s PSA was significantly improved after 32 months of using the original abiraterone.
Switching to domestic abiraterone, the PSA level increased, which suggests that there is a difference between our generic and original abiraterone
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The original abiraterone is a new endocrine drug recommended by the international and domestic guidelines for the treatment of advanced prostate cancer.
Compared with the imitation products, it has excellent evidence of efficacy and safety
.

In the real world, imitation abiraterone has more serious adverse events than the original abiraterone6-7
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Case provider: Professor Ma Hong, Professor Ma Hong, Deputy Chief Physician, Department of Urology, Beijing Hospital, Deputy Chairman, Urology Committee, Beijing Cancer Research Association, Deputy Chairman, Urology Committee, Beijing Anticancer Association, Youth Committee of Urology and Oncology, Beijing Anticancer Association, Youth Committee, Beijing Association of Chinese and Western Medicine Andrology, Youth Committee, Chinese Research Hospital Association Urology And the andrology shockwave group member, "Chinese Journal of Sexuality", the outstanding teacher of Peking University Medical Department, National Taiwan University Hospital, and the visiting scholar of Charlotte Hospital in Berlin (Professor Wan Ben).
For patients, part of the payment pressure is reduced
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Generally, the bioavailability of a generic drug is considered to be bioequivalence within 80%~125% of the bioavailability of the original drug.
However, the determination of bioequivalence will lead to the bioequivalence of the generic drug and the original drug in principle.
There are differences in availability, and it will lead to greater differences in bioavailability between generic drugs
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In this case, after the patient switched to domestic abiraterone, the PSA level increased, suggesting that bioequivalence ≠ clinical equivalence 8
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For some elderly patients with prostate cancer, there are many basic comorbid diseases and the quality of life is generally poor.
If the dressing is changed for non-medical reasons, the risk of disease fluctuations and complications will be significantly increased
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Therefore, clinically, we should focus on the above types of patients, and carefully weigh the choice of generic drugs or original research drugs9-12
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Looking forward to the continuous technological innovation of China's pharmaceutical industry in the future, domestically produced generic drugs can be comparable to the original drugs in variety and quality, and guarantee more patients' benefits
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In addition, this case suggests that in combination therapy with abiraterone, glucocorticoid replacement can lead to sustained PSA reduction in patients
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Reviewer: Professor Wan Ben Professor Wan Ben Chief Physician of Urology Department of Beijing Hospital Member of Oncology Committee of Chinese Medical Doctor Association Urology Committee Member of Urology Committee of Chinese Research Hospital Association Deputy Director of Beijing Anticancer Association Urology and Male Reproductive Oncology Committee Member of the Urology Expert Committee of the Beijing Medical Doctor Association Member of the Urology Professional Committee of the Cross-Strait Medical and Health Exchange Association Member of the Sino-Japanese Medical Science and Technology Exchange Association Director Case 2 Male with medical history, 69 years old
.

Main complaint: Physical examination found that PSA increased for 1 week
.

Past history: 8 years of coronary heart disease.
3 years ago, he underwent coronary stent implantation in an outside hospital, and long-term oral aspirin and pluvate antiplatelet therapy
.

Auxiliary examination laboratory examination: total prostate specific antigen (T-PSA) 149.
5ng/ml
.

Bone scan: the 3-5 anterior ribs on the right, the 3/6 anterior ribs on the left, the 7th posterior rib, the 9th posterior rib near the costal joints, the 10th thoracic vertebrae, and the 2/5th lumbar vertebrae with increased radiation uptake ( 10 locations)
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Enhanced MR of the prostate: Prostate cancer may be large, the tumor has broken through the capsule, involving the seminal vesicle glands
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There are multiple swollen lymph nodes beside the bilateral iliac vessels, and metastasis is possible
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The bones of the lumbar vertebrae 2 and 5 are destroyed, and the metastasis may be large
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Figure Whole body bone imaging puncture pathology: prostate cancer, 12/13 (+), Gleason score 4+5=9 points, some tumor infiltrating nerves can be seen
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Diagnosis Results First diagnosis (June 2014): high-risk mHSPC (T3bN1M1)
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Second diagnosis (February 2015): mCRPC
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After treatment, he received bicalutamide 50mg Qd x 2w + goserelin 10.
8mg in June 2014
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Joined the LATITUDE study in July 2014, and the PSA was as low as 4.
02 ng/ml
.

In February 2015, the PSA increased to 14.
73 ng/ml, the trial group was released, unblinded, and confirmed to be the placebo group; then the patient received goserelin 10.
8mg + bicalutamide 50mgQd, 6 months later, the PSA reached the lowest 4.
21 ng/ml
.

In December 2015, the PSA rose to 9.
12 ng/ml, and bicalutamide was stopped.
The PSA level fell back to 6.
5 ng/ml in February 2016.
After 8 weeks, the PSA rose again to 11.
97 ng/ml
.

In June 2016, the patient received abiraterone 1000 mg Qd + prednisone 5 mg Bid, and the PSA gradually decreased to a minimum of 0.
75 ng/ml
.

In November 2017, the prednisone 5mg Bid was replaced with dexamethasone 0.
75mg Qd, and the PSA was 2.
36ng/ml
.

In December 2019, the PSA level slowly increased to 18.
49 ng/ml, and the patients who started the docetaxel + dexamethasone regimen completed 9 cycles of chemotherapy in the DP regimen, and the PSA dropped to 1.
72 ng/ml
.

In July 2020, the patient underwent pelvic magnetic resonance and PSMA-PET/CT examination due to dull abdominal pain and showed new seminal vesicle metastases.
After radiotherapy, it was found that the seminal vesicle cancer became smaller and the symptoms of pelvic pain disappeared
.

In November 2020, the PSA increased to 3.
4ng/ml, with new-onset pain in the ribs, and oral analgesics were needed for relief
.

Re-examination of PSMA and SSTR-PET/CT found new metastases on the posterior ribs and multiple liver lesions; CT-guided needle biopsy of liver lesions; pathology: Infiltration of cancer cells in the liver tissue
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On November 23, 2020, docetaxel 120mg + carboplatin 450mg chemotherapy, neutropenia and thrombocytopenia CTCAE grade IV occurred after 1 week of chemotherapy, and symptomatic and supportive treatment improved after 1 month
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Enzalutamide treatment was started in January 2021
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……Picture Analysis of changes in serum PSA levels in prostate cancer patients during different treatment regimens.
Case analysis: This patient was found to have multiple bone metastases throughout the body at the time of treatment, and his Gleason score was 4+5=9, which is in line with the high-risk and high-tumor burden mHSPC diagnosis, 2014 The patient was enrolled in the LATITUDE study in July
.

The LATITUDE study is a multicenter, phase 3, randomized, double-blind, placebo-controlled trial in newly diagnosed high-risk metastatic prostate cancer patients who have not been treated with hormones
.

The final analysis showed that the median OS of patients receiving ADT+AAP in the first line was 4.
5 years, which was 16.
8 months longer than that in patients receiving ADT in the first line
.

Therefore, whether the patient receives ADT alone or combined with androgen blockade therapy (CAB) is not enough, the treatment plan of ADT combined with abiraterone should be recommended first
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Figure LATITUDE study results.
Patients were treated with abiraterone combined with prednisone in the mCRPC stage.
After several years of treatment, PSA was well controlled.
The intermediate prednisone was replaced with dexamethasone, and the use of abiraterone was continued until symptoms and imaging progress
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After undergoing various treatments such as new endocrine therapy, patients have achieved a long-term survival of up to 7 years1
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Case provider: Professor Mi Yue, Professor Mi Yue, Ph.
D.
Attending Physician in Department of Urology, Peking University First Hospital, Peking University Institute of Urology, Specializing in minimally invasive treatment of urinary tract tumors, endovascular treatment of prostate hyperplasia, urinary calculi, and comprehensive treatment of advanced tumors Treatment
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Has been engaged in clinical medical treatment, teaching and scientific research in urology
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In 2018, he participated in the 32nd "Chinese Urology Engineering Training Course" to visit USC in the United States
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He has published a total of 6 domestic core journal papers and SCI papers, participated in the writing of 3 urology monographs, and translated 4 urology monographs
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Comment (Professor Zhang Qian) This patient was diagnosed with mHSPC for the first time, and the disease rapidly progressed to mCRPC after 7 months of ADT treatment
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Most high-risk/high tumor burden mHSPC patients respond to ADT at the beginning of treatment, but develop mCRPC after 9-15 months of ADT treatment
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Therefore, for high-risk mHSPC patients, clinical endocrine therapy should be used earlier
.

Regardless of whether the PSA decreased by more than 30% or 50% as the cutoff value, the prognosis of patients who achieved an early PSA response (EPR) was significantly better than that of patients who did not achieve EPR
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When the patient entered the mCRPC stage and treated with the ADT+AAP regimen for 1 month, the patient's PSA level decreased by 73.
4%, achieved EPR and PSA decreased by >50% from baseline
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Since then, the program has continued to maintain relative tumor control and stable disease in the past 3 years
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The patient has undergone new endocrine therapy, chemotherapy, radiotherapy, combined chemotherapy and new endocrine sequential therapy, and achieved good therapeutic effects and achieved long-term survival
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Reviewer: Professor Zhang Qian, Professor Zhang Qian, Deputy Director, Peking University Institute of Urology, Deputy Director, Peking University First Hospital, Deputy Director of Urology, Peking University First Hospital, Dean, Peking University Binhai Hospital, Peking University Medical Department, Director of Hospital Management Office, Guo Yinglu, Deputy Director, Urology Development Foundation, Chinese Physician Deputy Chairman of the Youth Committee of the Urology Branch of the Association Member of the Minimally Invasive Group of the Chinese Medical Association Urology Branch Member of the National Health and Family Planning Commission Urological Endoscopy Technical Expert Group During the treatment of cancer patients, by monitoring the changes in PSA levels and imaging examinations, the patient’s sensitivity to androgens and the progress of the disease can be understood in time, providing a basis for the adjustment of treatment plans and prognostic judgment
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The original abiraterone is a new endocrine drug recommended by international and domestic guidelines for the treatment of advanced prostate cancer.
The first choice is the original abiraterone, which can bring significant PSA decline and sustained disease control to patients
.

Remarks: Abiraterone acetate tablet is referred to as Abiraterone in the text.
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Mi Yue, et al.
Chinese Journal of Urology.
2021;42:19-23.
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Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline.
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European Association of Urology.
Guidelines on Prostate Cancer.
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NCCN Clinical Practice Guidelines in Oncology(NCCN Guidelines®) .
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.
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CSCO,2021 Prostate Cancer Diagnosis and Treatment Guidelines 6.
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Ryan CJ, et al.
Lancet Oncol.
2015; 16(2):152-160.
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Huang Lang, et al.
Northern Pharmaceuticals.
2011;08(8): 83-84.
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resented by Prof.
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