Case sharing Abiraterone original research drug vs. generic drug, which one is better?

Once Zeke® (Abiraterone Acetate Tablets) was launched, it was soon recommended by domestic and foreign guidelines for metastatic castration-resistant prostate cancer (mCRPC) and high-risk metastatic hormone-sensitive prostate cancer (mHSPC) with its excellent efficacy data.
First-line treatment options
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As China's first new endocrine therapy drug for prostate cancer, its excellent clinical efficacy has caused domestic companies to rush to imitate it
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In the real world, is the original research drug and the generic drug better? This time, I will bring you 2 cases from the real world to share with readers
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Case 1, a 77-year-old male with medical history, chief complaint: PSA has been elevated for more than 4 years
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History of present illness: The patient's physical examination found that the PSA was elevated more than 4 years ago, about 5ng/ml, and then increased to 8ng/ml, which was not taken seriously
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In January 2019, another physical examination showed that PSA=43.
6ng/ml.
The outside hospital failed to puncture in time due to low platelets.
After 2 months, PSA increased to 108ng/ml, and the patient had long-term poor urination and increased nocturia (2-3 times) , Then went to our hospital for treatment
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Digital rectal examination: The prostate is enlarged, and the surface of the double lobe touches many raised nodules (the right lobe is more obvious), the texture is hard, and it is closely related to the rectum
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Auxiliary examination laboratory examination: platelets (PLT) 102 x 109/L, alkaline phosphatase (AKP) 160U/L, alanine aminotransferase (ALT) 77U/L
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Ultrasound: prostate 49*47*32mm, protruding into the bladder, considering malignant tumor, involving the right seminal vesicle
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MRI: Prostate cancer involves both seminal vesicles and is closely related to the right wall of the pelvis and rectum
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Figure 1 MRI results of pathological biopsy: (12 needles of prostate puncture) prostate acinar adenocarcinoma, Gleason score 4+4=8 points
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SPECT/CT: Multiple bone metastases throughout the body (T11, L2, right iliac, sacrum, left pubis)
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Diagnosis (high risk) metastatic hormone-sensitive prostate cancer (cT4N0M1b)
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Treatment after 1.
The patient was a high-risk mHSPC and was treated with imitation abiraterone (1000 mg qd po)
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On September 9, 2019, the PSA dropped to 1.
59 ng/ml after the initial treatment.
However, only 6 months after the initial treatment, the PSA began to gradually increase.
On July 27, 2020, the PSA rose to 54.
7 ng/ml
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Figure 2 PSA level after treatment with imitation abiraterone 2.
Further review of PET-CT showed that: prostate cancer, the right seminal vesicles may be involved, and the lesions reduced compared with the previous ones; multiple bone metastases, new L3 metastases
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Figure 3 PET-CT results 3.
The patient's serum testosterone reached castration levels, confirmed PSA progression and new bone metastases, and a clear diagnosis of mCRPC.
After communicating with the patient, in August 2020, he was given the original research abiraterone ( 1000mg qd po) treatment
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4.
Follow-up results: PSA continued to decrease.
The last two PSA levels were 0.
37ng/ml and 0.
25ng/ml, and the testosterone level dropped to 0.
5nmol/L
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The imaging examination after 5 months of medication showed that the right seminal vesicles of MRI prostate cancer were basically clear; after 6 months of medication, ECT showed that the lesions were stable, the L3 lesions disappeared, and the L2 lesions were smaller than before
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 Figure 4 PSA level after treatment with original abiraterone Figure 5 Testosterone level after treatment with original abiraterone Figure 6 MRI results after treatment with original abiraterone Later, the PSA began to rise only 6 months after the decline, which was much shorter than the time from the experimental group in LATITUDE study 1 to PSA progression; and further PET-CT reexamination revealed the appearance of new metastatic lesions
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We can’t help but reflect: Is the patient’s own disease progressing faster, or is the patient not getting enough benefit from the treatment of abiraterone due to the difference in clinical efficacy between the imitation product and the original drug? After communicating with the patient, he was given the original abiraterone treatment, and the PSA level continued to decrease.
After 5 months of treatment, a reexamination of the MRI revealed that the right seminal vesicles were involved in remission.
A bone scan after 6 months of treatment indicated that the bone lesions were reduced.
The latest reexamination indicated that the bone lesions were stable
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The original research of abiraterone enables rapid control of patients' PSA levels and metastatic lesions, which once again confirms the efficacy of the original research of abiraterone in real-world clinical practice
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From the perspective of mechanism of action 2-6, androgens in tumor tissues are significantly higher than physiological levels.
Even if the serum castration level has been reached, local androgens in tumors can still exist and activate androgen signaling pathways
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The original abiraterone can block androgen production from all sources, effectively reducing androgen levels in the plasma and bone microenvironment
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Figure 7 Abiraterone can effectively reduce androgen levels in plasma and bone microenvironment.
From the analysis of clinical efficacy data, LATITUDE study 1 confirmed that compared with the control group, Abiraterone combined with prednisone + androgen deprivation therapy (ADT) prolonged The time from mHSPC patients to PSA progression was 4.
5 times (33.
2 vs 7.
4 months, HR=0.
3, P＜0.
001), and the median imaging progression-free survival (rPFS) was significantly extended to 33 months, and the risk of tumor metastasis progression in Asian patients was reduced Nearly 70%, it helps patients with metastasis to obtain a longer survival time
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Figure 8 Time to PSA progression Figure 9 rPFS results The original abiraterone drug and the generic drug have similar "shapes", but the "quality" is different
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The research and development of the original research drug needs to go through long preclinical research and clinical research, such as compound purification, short-term animal experiment, long-term animal experiment, clinical phase I~III research, but generic drugs do not require the completion of large-scale clinical trials, only through The bioequivalence study is submitted for approval and listing
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The bioavailability of the generic drug is within 80%~125% of the bioavailability of the original drug.
Both are considered to be bioequivalent, but the determination of the bioequivalence will lead to the bioavailability of the generic drug and the original drug in principle.
There are differences, and will lead to greater differences in bioavailability between generic drugs, so bioequivalence≠clinical equivalence7
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Case provider: Professor Xu Lei, Professor Xu Lei, Associate Chief Physician of Department of Urology, Zhongshan Hospital, Fudan University, Doctor of Oncology, Barts School of Medicine, Queen Mary College, University of London, UK Honorary Academic Urologist, Department of Urology, University College Hospital, London Honorary Academic Urologist, Fudan University Shanghai Medical College Master of Science intern in Urology, Archbishop's Hospital, Columbia University, New York, USA Association member comment (Xu Zhuoqun) As Abiraterone has been widely recognized in clinical practice, China has already approved a variety of Abiraterone generic drugs for listing
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However, the original drug and the generic drug are not 100% identical.
Although the generic drug and the original drug are bioequivalent, bioequivalence does not mean clinical equivalent
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In this case, the disease progressed after the use of domestic abiraterone.
After switching to the original abiraterone, the condition was significantly alleviated, which proved the advantages of the original abiraterone in clinical efficacy
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Bioequivalence has limitations in research objects
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Except for special drugs such as anesthetics, class I psychiatric drugs, highly toxic drugs, women and children drugs, the bioequivalence test of general drugs selects healthy male subjects aged 18 to 40.
Therefore, the results only represent health.
The bioavailability of the population cannot be directly applied to patients in the real world
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The LATITUDE study confirmed the significant benefits of abiraterone for high-risk mHSPC patients.
For newly diagnosed high-risk mHSPC patients, if the original research abiraterone is first treated, the patient's prognosis may be better
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Reviewer: Professor Xu Zhuoqun, Professor Xu Zhuoqun, Chief Physician of the Department of Urology, Wuxi People's Hospital, Chief Physician of Wuxi, Professor of Nanjing Medical University, Member of the Prostate Cancer Group of the Chinese Society of Anticancer Society of Urinary and Male Reproductive Tumors, Chinese Society of Clinical Oncology (CSCO) Prostate Cancer Member of the Expert Committee Member of the 4th Sexual Medicine Specialty Committee of the Chinese Society of Sexuality Member of the 2nd Society of Organ Transplantation of Jiangsu Medical Association Deputy leader of the group, member of the 3rd Andrology Branch of Jiangsu Medical Association, 2nd Chairman of Wuxi Urology Society, is good at diagnosis and treatment of urological tumors such as kidney cancer, bladder cancer and prostate cancer.
There are in-depth studies on stones, congenital malformations, and benign prostatic hyperplasia
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Proficient and good at minimally invasive surgery in urology
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Case 2 A 76-year-old male with medical history, presented to the outpatient clinic on May 13, 2018
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Main complaint: Progressive dysuria for 10 years, worsened by 2 weeks
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Past history: Past history of cerebral infarction, suffering from hypertension for more than 10 years, self-reported oral medication control is acceptable
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Digital rectal examination: no tenderness, 2 degree anal examination of the prostate, toughness, no obvious nodules
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Auxiliary examination laboratory examination: PSA 383.
352ng/ml
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Ultrasound: Prostatic hyperplasia
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MRI: Peripheral zone with low signal intensity to the left, abnormal signal between the right acetabulum, ischial branch, inferior pubic branch, and left femoral trochanter, consider metastasis
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ECT: Multiple bone density abnormalities in the sternum, ribs on both sides, spine, and pelvis, consider the possibility of multiple bone metastases
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Pathological biopsy: prostate adenocarcinoma, Gleason score 4+4=8 points
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Diagnosis (high risk) metastatic hormone-sensitive prostate cancer, cT2cN1M1b
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After treatment 1.
From May 2018 to December 2018, the traditional combined androgen blockade (CAB) regimen: goserelin + bicalutamide
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The follow-up results showed that after only 5 months of medication, PSA progressed, and 3 consecutive increases (testosterone was at the castrated level), confirming to enter the mCRPC stage
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Figure 10 2018.
5-2018.
12 PSA follow-up results 2.
From January 2019 to July 2020, treatment with abiraterone acetate
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The patient was first treated with the original abiraterone, and was replaced with the imitation abiraterone in the middle.
The reason and time are unknown
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The results of the PSA follow-up showed that the PSA has been continuously increased since January 2020, confirming the progress of PSA
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Figure 11 2019.
1-2020.
7 PSA follow-up results 3.
Starting from September 2020, docetaxel 120mg d1/q3w + prednisone 5mg bid treatment
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From August 2020 to February 2021, PSA follow-up results suggest that PSA continues to rise
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Figure 12 2020.
8-2021.
2 PSA follow-up results 4.
2 From February to May of 21, the original abiraterone treatment was changed again.
The follow-up results showed that PSA continued to decline
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Figure 13 2021.
2-2021.
5 PSA follow-up results Case thinking After the patient was diagnosed with mHSPC, the traditional CAB scheme was first adopted.
However, it only took half a year and quickly progressed to the mCRPC stage, suggesting that high-risk mHSPC patients should be treated with new endocrine drugs as soon as possible
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In this case, the original abiraterone was first used in the mCRPC stage, and the PSA was well controlled, and then the imitation product was replaced by oneself.
PSA progress occurred.
It is impossible to judge whether the disease itself is progressing or the imitation product is not effective.
After chemotherapy, the PSA continues to rise.
Trying to switch back to the original research product program, PSA has been significantly relieved, and it is also impossible to judge whether it is the difference between the original research drug and the imitation product, or whether chemotherapy has played a role in the middle
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It can be seen that although the original product is only replaced with imitation products, when the disease is well controlled, the replacement of the treatment plan greatly increases the complexity of clinical judgment! Case provider: Professor Zhou Yongqiang, Professor Zhou Yongqiang, Deputy Chief Physician, Suzhou Ninth People's Hospital, Suzhou University, Bachelor of Tianjin Medical University, Master of Nanjing Medical University, Shanghai Changhai Hospital for advanced studies, published several domestic core journals and hosted two reviews on prostate cancer topics ( Zhuang Junlong) During the treatment of mCRPC, the patient changed from the original abiraterone to the imitation abiraterone by himself.
The reason and time are unknown.
The PSA decreased first and then increased continuously, confirming the progress of PSA
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Does the disease progression mean that Abiraterone has failed? The answer is unknown
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Subsequently, the patient received chemotherapy, but the PSA continued to rise.
After switching to the original abiraterone, the PSA began to decline
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Studies have shown that the combination of abiraterone combined with prednisone (AAP) + docetaxel combined with prednisone (DP) + AAP can relieve the PSA of patients and prolong the survival time of patients 8
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But combined with the patient's treatment process: after chemotherapy, the patient was again sensitive to abiraterone? Or is it due to the fact that the previous patient replaced the imitation abiraterone on his own, leading to poor efficacy and causing disease progression? The answer is also unknown! The original research abiraterone was listed in China in January 2016, has been approved in 108 countries, and is widely used in more than 470,000 prostate cancer patients worldwide, and has accumulated rich real-world data, especially the Chinese own evidence-based , Confirming the stable efficacy and safety in the real world
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Reviewer: Professor Zhuang Junlong Professor Zhuang Junlong Associate Chief Physician of Department of Urology, Nanjing Gulou Hospital, Master's Supervisor, Doctor of Medicine, Nanjing University, Postdoctoral Fellow, Nanjing Gulou Hospital Urology, Prostate Cancer Group Deputy Leader, National Natural Science Foundation of China General Program, Youth Fund Winner Jiangsu Province The winner of the Outstanding Youth Fund of the Natural Science Foundation of China, Nanjing Young Talents for Health, Member of the Youth Committee of Jiangsu Urology Branch, presided over 9 various funds, and the first author published 12 SCI papers.
The main focus is on the precise diagnosis and treatment of urinary tumors, especially prostate cancer.
For the treatment of high-risk mHSPC patients and mCRPC patients, the efficacy of Zeke® (Abiraterone Acetate Tablets) has been widely recognized in clinical practice: positive efficacy, tolerability, and safety
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Although generic drugs have been approved continuously in recent years, there are still differences in the efficacy of generic drugs and original drugs in clinical practice
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The above two cases remind us that the original research abiraterone should be used as soon as possible for the treatment of mHSPC patients, which can prolong the survival of the patients, and at the same time can reduce the complexity of clinical efficacy determination and help a stable doctor-patient relationship
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Remarks: Abiraterone acetate tablet is referred to as Abiraterone in the text.
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