Case sharing: Abiraterone has a significant effect of deeply relieving PSA, and the quality of the original drug is better

As the second largest male malignant tumor in the world, the incidence of prostate cancer in China is increasing year by year, and many patients have already entered the middle and late stages when they are diagnosed
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Most patients will eventually progress to castration-resistant prostate cancer (CRPC) after receiving endocrine therapy, and clinicians need to formulate treatment strategies based on evidence-based medical evidence and the patient's comprehensive situation
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The original abiraterone acetate tablet has been unanimously recommended by domestic and foreign guidelines for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) due to its excellent efficacy
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This issue brings you 2 cases from the real world to share for readers
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Case 1, a 67-year-old male with a medical history, chief complaint: diagnosed with prostate cancer for more than 2 years
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The patient with a history of present illness was found to have abnormal prostate in a foreign hospital in November 2019, PSA 46ng/ml, and underwent prostate puncture in a foreign hospital on November 19, 2019.
Postoperative pathology showed adenocarcinoma tissue in all 12 tissues, and the Gleason score was 5+4= 9 points, local tumor involving the nerve
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On November 26, 2019, SPECT/CT (201911451) in an external hospital showed multiple bone metastases throughout the body
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Past history of diabetes mellitus for 3 years, hypertension for 1 year
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More than 10 years ago, "intestinal trauma surgery" was performed in a foreign hospital
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On digital rectal examination, the prostate gland was enlarged and the central sulcus was not reached
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The surface of the two lobes touched multiple raised nodules (more obvious in the right lobe), which were hard in texture and closely related to the rectum
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Finger cuffs are blood-stained
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The auxiliary examination ECT showed: T11, L2, right ilium, sacrum and left pubic bone showed osteogenic bone destruction with abnormal concentration of imaging agent
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Considering multiple bone metastases throughout the body, radionuclide internal radiation therapy is recommended
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Figure 1 ECT examination results Diagnosis results of prostate cancer treatment After 1, November 2019 to July 2020, androgen deprivation therapy (ADT) + bicalutamide treatment was given, the PSA value decreased at the early stage of treatment, May 2020 PSA rose again
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In June 2020, the testosterone result was 0.
5nmol/L
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Figure 2 Changes in PSA values ​​of patients during treatment 2.
The results of re-examination PET-CT showed that, in prostate cancer, the right seminal vesicle may be greatly involved, and the lesions were smaller than before
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The patient had new L3 bone metastases, suggesting that the patient's disease had progressed to the mCRPC stage
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Figure 3 PET-CT results 3.
From July 2020 to February 2021, the replacement therapy was ADT+chemotherapy
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The imaging examination in October 2020 showed multiple bone metastases throughout the body; the posterior wall of the bladder was thickened, which was smaller than the results in July 2020; mild fatty liver and liver calcification
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Chemotherapy was stopped after 8 cycles of chemotherapy
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Figure 4 Changes in PSA values ​​of patients during
chemotherapy
In August 2021, domestic abiraterone was discontinued and oral enzalutamide was changed to oral administration for 1 month, but the drug was discontinued due to side effects such as general discomfort, general pain and poor appetite
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Genetic testing revealed a TP53 mutation
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Figure 5 Changes in PSA values ​​of patients during treatment with domestic abiraterone Metastasis, multiple bone metastases throughout the body, and tumor heterogeneity in some lesions, please combine clinical practice
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6.
In September 2021, the patient continued to receive ADT+ new endocrine therapy, and the domestic abiraterone was changed to the original research abiraterone treatment, and the patient's PSA decreased
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Considering the patient's TP53 gene mutation, the original research abiraterone + PD-1 will be used in December 2021
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Figure 6 Case analysis of patient's PSA value changes After the patient was diagnosed with advanced prostate cancer, ADT+bicalutamide was first treated, but after a period of treatment, the patient entered the mCRPC stage
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The patient was first treated with domestic abiraterone + ADT, but the patient's PSA value did not drop but rose, and bone scan showed that the bone metastases were aggravated
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Subsequently, the patient was switched to enzalutamide + ADT treatment, but the drug was quickly discontinued due to excessive side effects
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The patient subsequently received the original research abiraterone acetate + ADT treatment, and the patient's PSA decreased
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In December 2021, based on the results of genetic testing, the patient received the original research abiraterone acetate + PD-1 treatment
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This suggests to us that there are still differences between generic drugs and brand-name drugs despite their similar ingredients
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We know that the bioavailability of the generic drug is within 80%~125% of the bioavailability of the original drug, both of which are considered to be bioequivalent, but bioequivalence will lead to the bioavailability of the two in principle.
Differences exist and can result in greater differences in bioavailability between generics, so that bioequivalence ≠ clinical equivalence1
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In addition, due to the limitations of bioequivalence in research subjects2, these studies are often based solely on healthy populations, which are different from patients.
Therefore, caution should still be exercised when selecting generic drugs for patients
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Case Provider: Dr.
Xu Lei Expert Profile Dr.
Xu Lei Deputy Chief Physician, Department of Urology, Zhongshan Hospital Affiliated to Fudan University, Master's Supervisor Master of Surgery, School of Medicine, New York Columbia University Archbishop's Hospital Urology Intern, U.
S.
A.
Chinese Medical Association Urological Association (CUA) Youth Committee Oncology Group Expert Comments on Advanced prostate cancer patients will eventually progress to the CRPC stage.
For mCRPC patients, control should be done as much as possible disease progression, prolong the survival time of patients, and improve the quality of life of patients
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At present, abiraterone acetate has been unanimously recommended by domestic and foreign guidelines for the treatment of patients with mCRPC.
Therefore, in this case, after the patient entered the stage of mCRPC, abiraterone was preferentially selected for treatment
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As a generic drug, the biggest advantage of domestic abiraterone is that it is cheap, which can reduce the economic burden of patients
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However, in this case, after the patient was treated with domestic abiraterone, the disease could not be well controlled, and the PSA continued to rise.
Therefore, it was considered to replace the original abiraterone acetate treatment, and the follow-up treatment effect was remarkable
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This suggests that patients who use the original abiraterone acetate as soon as possible may benefit more
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Therefore, in clinical practice, how to balance the economic burden of patients and the effect of drug treatment should be considered by every clinician
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Expert review: Professor Guo Jianming's expert profile Professor Guo Jianming Chief physician of the Department of Urology, Zhongshan Hospital Affiliated to Fudan University, doctoral supervisor Member of the Standing Committee of the Male Reproductive Cancer Special Committee, Member of the Kidney Cancer Research Group, CSCO Prostate Cancer, Urothelial Cancer Special Committee, Standing Committee Member of the Cancer Special Committee Yu
.

History of present illness In August 2016, due to dysuria, frequency and urgency of urination for more than half a year, he was admitted to Xiangya Hospital of Central South University, TPSA was 156.
78ng/ml, whole body bone scan showed multiple bone metastases throughout the body, and further prostate puncture was performed to confirm the diagnosis of prostate acinar Cancer with multiple bone metastases throughout the body
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On digital rectal examination, the prostate gland was enlarged in degree II, with no palpable enlarged nodule, firm in texture, disappearance of the central sulcus, and inconspicuous tenderness
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Auxiliary examination Whole body bone scan: abnormal radioactive concentration was seen in the skull (right parietal bone), left fifth anterior rib, multiple lumbar vertebrae, left sacroiliac bone, right femur, and no abnormal radioactive concentration in the remaining bones
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Laboratory examination: The results in August 2016 were that serum PSA was 156.
78ng/ml; testosterone was 2.
13ng/ml
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Prostate biopsy: prostate acinar carcinoma, Gleason score 3+4=7
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The diagnosis result was acinar carcinoma of the prostate, with multiple bone metastases throughout the body, and it was an advanced prostate cancer with a high tumor burden
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After treatment 1.
In August 2016, the patient received goserelin + bicalutamide endocrine therapy in a foreign hospital after being diagnosed with prostate cancer, and was regularly reviewed
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2.
In August 2017, the disease entered the stage of castration resistance, and received ADT + domestic abiraterone + prednisone + fluzoparib (enrolled in the clinical study) treatment, and the patient's PSA continued to rise
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In November 2017, the patient came to our hospital for re-examination and continued the previous treatment
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Patients were followed up monthly, but PSA had been trending upward
.

Figure 7 Changes in PSA values ​​of patients during treatment with domestic abiraterone 3.
In December 2018, the generic drug of abiraterone was replaced with the original abiraterone acetate to continue treatment.
Up to now, the patient's PSA has dropped to 0.
03ng/ml, and his body is relatively weak.
healthy
.

Figure 8.
Case analysis of the change trend of PSA , but the patient's PSA continued to rise.
One year later, the patient was replaced by the original research abiraterone acetate on the advice of the clinician to continue the treatment.
The treatment effect was remarkable, and the PSA dropped rapidly
.

For drugs with high variability such as abiraterone acetate (that is, the intra-individual variability is not less than 30%3), it is more difficult for generic drugs to achieve bioequivalence
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Even if a generic drug achieves the same bioequivalence, it does not mean clinical equivalence
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This is because clinically abiraterone needs to be taken on an empty stomach4, while the generic drug trial does not need to meet the fasting condition5
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The study showed that in healthy subjects, the geometric mean of abiraterone AUC was increased by 5 times in the low-fat diet compared with the fasted state; and increased by 10 times in the high-fat diet
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Studies have shown that food significantly improves the bioavailability of abiraterone under fed conditions compared with fasting conditions6.
It is assumed that the bioequivalence test (BE) of the imitation abiraterone under high-fat diet conditions is completed, which is in line with 80%~125.
The %AUC equivalence standard (the 90% CI of the bioavailability [AUC, Cmax] GMR of the generic drug and the original drug falls within the range of 80%-125%, both are considered to be bioequivalent), and in clinical Taking generic abiraterone on an empty stomach may cause its AUC to decrease
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Therefore, domestic abiraterone as a generic drug is often difficult to achieve the therapeutic effect of the original abiraterone in clinical practice
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Case provider: Dr.
Jiang Shusuan Expert Profile Dr.
Jiang Shusuan Hunan Cancer Hospital/Deputy Chief Physician of Urology Department of Cancer Hospital Affiliated to Xiangya School of Medicine, Central South University, MD, MD, UC Davis Visiting Scholar, Chinese Anti-Cancer Association, Urogenital Tumors Professional Committee National Youth Committee Member of the Youth Committee of the Urology Professional Committee of the Hunan Medical Association Member of the Prostate Group of the Andrology Professional Committee of the Hunan Medical Association Expert commented that the patient's PSA continued to rise after receiving ADT + domestic abiraterone + prednisone + fluzoparib treatment in August 2017
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Because of the "Flare effect" of abiraterone, one would first wonder if the PSA increase was a temporary increase
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However, if the patient's PSA continued to rise within 12 months, the "Flare effect" was excluded, and it was considered whether the efficacy of generic drugs was poor
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Abiraterone acetate is an original imported drug, and many patients often refuse to use it because the price is too expensive and cannot afford the cost of treatment, and they choose generic abiraterone
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After the patient was treated with generic drugs, the patient's disease was not well controlled, which is undoubtedly bad news for the patient
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Therefore, under comprehensive consideration, clinicians should replace the original drug in a timely manner, so that the patient's PSA can be deeply relieved and the quality of life can be improved
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Now, abiraterone acetate has also entered the medical insurance, so that more mCRPC can afford the original research abiraterone, which is undoubtedly good news for mCRPC patients in China
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Commenting experts: Prof.
Wang Yinhuai Expert Profile Prof.
Wang Yinhuai Director of Urology Department, Second Xiangya Hospital of Central South University Director of Hunan Provincial Minimally Invasive Urology Clinical Research Center Member of Urology Branch of Chinese Medical Association Member of Urology Branch of Chinese Medical Doctor Association andrology and sexuality of Chinese Medical Association Member of the Medical Branch, Deputy Director of the Urology Professional Committee of the Hunan Medical Association and Head of the Robotics Group, Chairman of the Urology and Andrology Professional Committee of the Hunan Association of Traditional Chinese Medicine and Integrative Medicine, Standing Committee Member of the Urology Professional Committee of the Cross-Strait Exchange Society China Research Hospital Member of the Professional Committee of Urology of the Society, Member of the International Urolithic Federation, Member of the World Chinese Andrologists Association, Editor and Editor of the original research Abiraterone acetate tablet is a first-line treatment drug for advanced prostate cancer unanimously recommended by domestic and foreign guidelines, and its efficacy and safety are widely recognized in clinical practice
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The above two real-world cases remind us that for the treatment of mCRPC patients, we should use the original research abiraterone acetate for treatment as soon as possible, so as to better control the disease progression of the patients and improve the quality of life of the patients
.

Editor: TZY Review: Bing Xin Typesetting: XY Implementation: XY References: 1.
Huang Lang, et al.
Northern Pharmacy.
2011;08(8):83-84.
2.
http:// WS04/CL2093/229256.
html Notice of the General Administration on Issuing Three Technical Guiding Principles for Selection and Determination of Oral Solid Oral Reference Preparations (No.
61, 2016).
3.
Su Jing, et al.
China Journal of New Drugs.
2019; 28 (22):2693-2697.
4.
Instructions for Abiraterone Acetate.
5.
Li Xingang, Zhao Zhigang.
The Difference Between Original Brand Drugs and Generic Drugs from the Perspective of Clinical Efficacy.
Drug Evaluation.
2013(10):12:8-21.
6.
Kim N Chi KN, et al.
J Clin Pharmacol.
2015;55(12):1406-14.