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Small cell lung cancer (SCLC) accounts for about 15%¹ of lung cancer incidence¹, and its high degree of malignancy, fast growth, and easy metastasis are a "difficult bone"
in lung cancer treatment.
For many years, the treatment of SCLC has been limited to traditional chemoradiotherapy, but traditional chemoradiotherapy can not significantly prolong the overall survival of SCLC patients, and the advent of immunotherapy has opened up a new path
for the treatment of SCLC.
In recent years, China's self-developed PD-L1 inhibitor adebelimab has achieved remarkable results in the treatment of SCLC, and its phase III CAPSTONE-1 study was first announced positive results at the 2022 AACR conference, and was published
in the international top academic journal "Lancet Oncology" in May of the same year.
In this regard, Yimaitong specially invited Professor Shi Meiqi, PI of CAPSTONE-1 Research Sub-center, to comment on the results of CAPSTONE-1 research and share the experience of adebelimab medication
.
Professor Shi Meiqi
Chief physician, professor, master tutor of Jiangsu Cancer Hospital
Jiangsu Cancer Hospital/Jiangsu Institute of Cancer Prevention and Treatment Department of Medical Oncology Lung Cancer Subspecialty
Member of the Standing Committee of the Medical Oncology Branch of the China Association for the Promotion of International Exchanges in Healthcare
Member of the Expert Committee on Non-Small Cell and Small Cell Lung Cancer of the Chinese Society of Clinical Oncology (CSCO).
Member of the Clinical Research Committee of Oncology Drugs of the Chinese Anti-Cancer Association
Member of Internal Medicine Group of Lung Cancer Professional Committee of Chinese Anti-Cancer Association
Member of Thoracic Cancer Branch of China Association for the Promotion of International Exchange in Healthcare
Vice Chairman of the Professional Committee of the Pan-Yangtze River Delta Thoracic Cancer Alliance
Member of the Standing Committee of the Pulmonary Small Nodular Molecular Marker Collaboration Group of the Tumor Marker Professional Committee of the Chinese Anti-Cancer Association
Vice Chairman of MDT Committee of Pulmonary Nodules and Lung Cancer of Jiangsu Research Hospital Association
Member of the Standing Committee of the Lung Cancer Professional Committee of Jiangsu Anti-Cancer Association
Member of the Standing Committee of the Respiratory Rehabilitation Professional Committee of Jiangsu Rehabilitation Medical Association
Deputy leader of the Lung Cancer Group of the Oncology Branch of Jiangsu Medical Association
Member of the Lung Cancer Group of the Cancer Chemotherapy and Biological Therapy Branch of Jiangsu Medical Association
Member of Lung Cancer Group of Respiratory Disease Branch of Jiangsu Medical Association
Member of the Nasopharyngeal Cancer Professional Committee of Jiangsu Anti-Cancer Association
Member of Tuberculosis and Respiratory Disease Branch of Nanjing Medical Association
Scientific Committee Member of the East-West Lung Cancer Collaborative Organization (E-WEST LC).
Member of the International Lung Cancer Association and member of ASCO
Professional specialties: advanced tumor treatment, good at lung cancer medical treatment, participated in nearly 80 international and domestic multi-center clinical new drug research trials, published more than 100 papers, with the SCI paper published by the first author with the highest impact factor of 32.
976 points
.
Won two second prizes for new technology introduction from the Provincial Department of Health
The unique structure makes adebelimab safer Professor
Shi Meiqi
At present, the PD-L1 antibodies that have been marketed in China include atezolizumab, durvalumab and sugemalimab, and adebelimab will become the fourth PD-L1 antibody
on the market.
Both atezolizumab and duvalumab are lgG1 monoclonal antibodies, while sugemalimab and adebelimab are lgG4 antibodies, structurally different from the four PD-L1 antibodies
.
Adbelimab selects IgG4 antibody, and compared with IgG1 antibody, IgG4 antibody itself basically has no ADCC and CDC effect, which naturally avoids the ADCC and CDC effect to kill non-target cells
.
Adebelimab also eliminates ADCP effect, reduces ADCR effect, enhances immune efficacy, and reduces immune-related adverse reactions
by modifying the Fc segment of the antibody and removing the ability to bind to FcγR on the surface of macrophages.
From the antibody selection of adebelimab, it can be seen that the idea of antibody research and development is to pursue purer antibodies
.
With the increasing popularity of immunotherapy clinical applications, we have found that good efficacy is very important, but higher safety is also particularly important
.
With a wide range of immunotherapy products to provide patients with excellent efficacy and better safety of immunotherapy drugs, adebelimab may be a new choice
of double superior+.
Longer survival, the first-line treatment of adebelimab has won international recognition
Professor Shi Meiqi
The number of new lung cancer patients in China is as high as more than 800,000 every year, of which SCLC accounts for about 15% of the total incidence of lung cancer, although the proportion is not high, but the base of lung cancer patients is large, so SCLC patients are also a very large group, the treatment needs of this group exist in large quantities and cannot be ignored
.
In the stage of the disease, SCLC is divided into extensive stage and limited stage, and some patients with limited SCLC can achieve clinical cure through chemotherapy, radiotherapy, surgery and comprehensive treatment, but most SCLC patients are diagnosed in the extensive stage and have lost the opportunity for
cure.
The traditional treatment of extensive-stage SCLC is chemotherapy, and data show that the survival benefit of chemotherapy to patients is only about 10 months, which is difficult to exceed 1 year, and the treatment bottleneck is difficult to break through
.
In recent decades, with the continuous search of researchers, more than 30 large-scale phase III clinical studies of the first-line treatment of extensive-stage SCLC have been carried out at home and abroad, but no breakthrough has
been made.
Therefore, EP (etoposide + cisplatin) chemotherapy regimen has previously been the standard of care
for patients with SCLC.
In recent years, with the advent of immunotherapy, the survival of SCLC patients has improved, and the IMpower133 study achieved the first breakthrough in SCLC patients, the results showed that the median OS of the PD-L1 inhibitor atezolizumab combined with chemotherapy exceeded the 1-year mark, and in 2019, the CASPIAN study of durvalumab combined with chemotherapy obtained similar results, that is, the OS of first-line treatment of patients with extensive-stage SCLC in combination with immunotherapy was superior to chemotherapy²
。
Adbelimab is a PD-L1 antibody independently developed by Hengrui Pharmaceutical that uses lgG4 subtype for Fc segment modification, which removes the effect of ADDC, CDC, ADCP, reduces the effect of ADCR, and its antibody is purer and safer than other PD-1 or PD-L1 antibodies
.
The CAPSTONE-1 study is a randomized, double-blind, nationally multicenter, randomized controlled phase III study designed to evaluate the efficacy and safety
of adebelimab in combination with etoposide and carboplatin versus placebo plus etoposide and carboplatin in patients with extensive-stage SCLC.
Results showed that median OS was significantly longer in the adebelimab plus chemotherapy group than in the placebo plus chemotherapy group (15.
3 versus 12.
8 months; P=0.
0017), significantly reducing the risk of disease death by 28% (HR=0.
72).
At the same time, the 2-year OS rate in the adebelimab combination chemotherapy group was nearly 31%, allowing about one-third of patients to survive beyond two years, a result that chemotherapy could not achieve³.
The CAPSTONE-1 study was published this year in the international authoritative journal Lancet Oncology, marking that the research results have been highly recognized
by international authoritative medical organizations.
It is expected that after the launch of adebelimab, the treatment cost of immunotherapy for patients with extensive-stage SCLC will be greatly reduced, benefiting more Chinese SCLC patients
.
Reborn, adebelimab set a PFS record
of more than 3 years, Professor Shi Meiqi
Our center participated in the CAPSTONE-1 study, and to date, one of the enrolled patients has achieved sustained disease remission, and the patient has completed 35 cycles of adebelimab maintenance therapy with a PFS of 38 months with significant benefit
.
It is reported that the probability of survival of patients with extensive SCLC for more than 1 year is less than 50%, and this patient survives for more than 3 years and the condition has always remained stable, which can be described as a miracle, and adebelimab is the most important factor
in creating this miracle of life.
The efficacy and safety are comparable to imported drugs, and the cost performance of adebelimab is extremely high
After the new drug is approved for marketing, in addition to the efficacy that has attracted much attention, price is also the most concerned topic
for patients.
The price of some drugs is too high for patients to reach
.
In the field of SCLC treatment, before the domestic immune checkpoint inhibitor was not marketed, the clinical treatment mainly used atezolizumab and durvalumab, these two imported PD-L1 antibodies are expensive, most patients can not afford the high cost of treatment, patients may choose to use unapproved indications but more economical drugs for alternative treatment, and whether the alternative treatment plan can achieve the treatment goal, whether the safety is fully guaranteed and there is no standard answer.
With the "release" of domestic PD-1/PD-L1 antibody phase III clinical research data, it is not difficult to find that its efficacy and safety are no less than that of expensive imported PD-L1 antibodies
.
In the CAPSTONE-1 study, the median OS of patients with extensive-stage SCLC treated with the first line of adebelimab combined with chemotherapy for more than 15 months, and the incidence of immune-related adverse reactions (irAEs) was only 27.
8%, and the incidence of grade 3 irAEs ≥ ≤ 1.
8%
in terms of safety.
Looking at the safety data of the approved PD-1/PD-L1 antibodies, the incidence of irAE of adebelimab is low, and from the data, the safety profile of adebelimab is better than that of imported PD-L1 antibodies, which may be due to its structural Fc segment modification
.
It is expected that the price of adebelimab will be more affordable in the future, so that more patients can benefit
from this safe and effective immune checkpoint inhibitor treatment.
The development of China's innovative pharmaceutical industry has begun to take shape, and the road to leading the world is arduous
If there is no Chinese own brand, national products, then many areas of disease treatment in China will be subject to expensive foreign imported drugs, so domestic pharmaceutical companies need to independently develop national innovative drugs to improve drug access, and then benefit more patients
.
Since the reform and opening up, many leaders in the field of biomedicine have brought the technology they have mastered back to China through studying and researching abroad, and then carried out new drug research and development, and finally the national drug has been approved for marketing
.
Due to the hard work of these excellent scientific research staff, China's biopharmaceutical field has gradually developed from the previous "following and running" to "running along", and even some fields have achieved "leading"
.
Over the years, the anti-tumor drugs independently developed by domestic innovative technology enterprises have gained an international reputation, and this achievement is really hard-won
.
As a "leader" in the field of innovative drugs in China, Hengrui Pharmaceutical has developed a variety of innovative drugs in various fields to benefit patients
.
In a certain field of oncology, when only imported drugs are approved, the average monthly treatment cost of patients is as high as tens of thousands of yuan, which is unbearable for most patients, but with the successful research and development of domestic drugs, the cost of patient treatment will be greatly reduced
.
The most impressive is the PD-1/PD-L1 antibody
in the field of immunotherapy.
2018 is the first year of immunotherapy in China, nivolumab and pembrolizumab have been approved for marketing in China, after the market, its average monthly treatment cost is as high as 30,000 yuan, and the cost of a course of subsequent approval of durvalumab is even as high as 50,000-60,000.
After the advent of domestic PD-1 antibodies, the average monthly treatment cost does not exceed 3,000, which is 10-20 times lower than the price of similar foreign products, so the rise of national enterprises has truly benefited Chinese patients
.
In general, the development of the pharmaceutical industry is in full swing in recent years, and Chinese scientists still have a long way to go to lead the pace of this field!
Case introduction
Basic information
The patient is a 62-year-old woman
.
In June 2019, chest tightness and discomfort appeared without obvious causes, and it was not taken seriously
.
In early July 2019, cough began to appear, mainly dry cough, no obvious chest pain, hemoptysis, chills and fever
.
Local chest CT showed left lower lung mass.
Physical examination shows ECOG score of 0-1, low breath sounds in the left lung, remaining chest and abdomen (-), and no swelling of superficial lymph nodes
.
No family history
of tumors.
Ancillary examination
Blood routine, liver and kidney function, and electrolytes are basically normal
.
CEA 4.
84ng/mL、NSE 47.
94ng/mL
。 CT examination of the chest and abdomen showed that the soft tissue mass shadow in the left lower lung was unevenly strengthened, and the enlarged lymph nodes were seen in the left hilar; The right lower lung and the lingual lobe of the left lung are striped and inflamed
.
Multiple low-density shadows in the liver, insignificant strengthening, quasi-cysts
.
slight thickening of the gallbladder wall with strengthening, mimicking inflammation; cysts of both kidneys; The adrenal glands on both sides are hypertrophied, and the right internal branch is nodular.
There were no obvious abnormalities in cranial MR and bone scans
Bronchoscopic biopsy, pathological examination showed that the left hilum conformed to small cell malignant tumors, combined with immune indicators, and tended to small cell carcinoma
.
diagnosis
Left-sided small cell lung cancer with adrenal metastasis, cT2N1M1, stage IV.
, extensive stage
Treatment process
On July 22, 2019, patients participated in a randomized, double-blind, placebo-controlled, multicenter phase III clinical trial of adebelimab plus carboplatin + etoposide versus placebo plus carboplatin + etoposide first-line treatment of extensive-stage small cell lung cancer
.
2019-07-31The first cycle of induction therapy was started, and the treatment regimen was adebelimab (20 mg/kg, d1) combined with chemotherapy (etoposide 100 mg/m2 d1-3, carboplatin AUC=5 d1) (according to the blinding results); A total of 6 cycles of treatment were carried out and the process went smoothly
.
The efficacy was evaluated after the end of the treatment of the 2nd, 4th and 6th cycles, and PR was achieved.
From 2019-12-01 to 2021-07-28, "adebelimab (20 mg/kg, d1, Q3W) monotherapy maintenance therapy was given for a total of 35 cycles
.
During the review, the efficacy evaluation maintained the PR, and the process went smoothly
.
2021-07-28So far, the patient has not undergone anti-tumor treatment, and regular outpatient re-examination
.
At present, the patient is not significantly unwell
.
Efficacy evaluation
2019-07-10Before treatment
Treatment 2 cycles, PR
Treatment 4 cycles, PR
Treatment 6 cycles, PR
After maintaining 35 cycles, PR
Review after discontinuation, 2022-05-24, PR
Review after discontinuation, 2022-09-27, PR
Adverse reactions
During the treatment, the patient developed grade I pain in the left upper arm, perfected the shoulder joint MR, and no obvious abnormalities were seen, and irAE
was not considered for the time being.
During the period, the immune indexes such as blood routine, liver and kidney function, and thyroid function were basically normal, and the tumor indexes remained stable, basically close to normal values
.
Period: 2019-12-01 to 2021-07-28
Case summary and treatment experience
This patient with extensive small cell lung cancer (ES-SCLC) received adebelimab combined with chemotherapy first-line, and after sequential adebelimab maintenance therapy, he obtained a good therapeutic effect, achieved continuous PR and maintained it so far, the patient's survival time was more than 3 years, and during the follow-up period, the indicators were basically normal and well tolerated
.
References (swipe up to view):
1.
Yuan M, Zhao Y, Arkenau H T, et al.
Signal pathways and precision therapy of small-cell lung cancer[J].
Signal Transduction and Targeted Therapy, 2022, 7(1): 1-18.
2.
Paz-Ares L, Dvorkin M, Chen Y, et al.
Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial[J].
The Lancet, 2019, 394(10212): 1929-1939.
3.
Wang J, Zhou C, Yao W, et al.
Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial[J].
The Lancet Oncology, 2022, 23(6): 739-747.
Edited by Sierra
Reviewers: Felicia, Candy
Typesetting: Babel
Execution: Babel
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