CSCO 2021 PD-1 inhibitor slulizumab + bevacizumab has excellent initial performance for advanced liver cancer

*Only for medical professionals to read for reference.
What is the effect of the immune + anti-vascular combined program in the first and second-line treatment of advanced liver cancer? The combination of immunotherapy and anti-angiogenesis therapy has made significant progress in the diagnosis and treatment of advanced hepatocellular carcinoma in recent years, successfully breaking through the curative effect bottleneck of previous anti-angiogenic drug monotherapy
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At the 24th National Conference on Clinical Oncology and the 2021 CSCO Annual Conference, Professor Ren Zhenggang from Zhongshan Hospital of Fudan University reported a PD-1 inhibitor slulimumab (HLX10) combined with bevacizumab ( HLX04), the results of a phase II clinical study for the treatment of patients with advanced hepatocellular carcinoma
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The treatment of liver cancer in China still faces many difficulties, and more effective solutions are needed to solve the predicament.
According to the World Health Organization's 2020 Global Cancer Statistics Report (GLOBOCAN) data, China is still the country with the highest number of incidences and deaths of liver cancer in the world, and the incidence and incidence of liver cancer are The mortality rate ranks fifth and second among all malignant tumors, and most patients are already in the middle and advanced stages when they are diagnosed.
They have lost the opportunity for radical surgery, resulting in unsatisfactory prognosis for patients
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The etiology, epidemiology, biological behavior, clinical manifestations and treatment of liver cancer patients in China are significantly different from those of European and American countries.
Therefore, it is very important to independently explore the diagnosis and treatment strategies suitable for patients in China
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With the development and enrichment of diagnosis and treatment methods, the current diagnosis and treatment mode of advanced liver cancer has changed from the previous single targeted/interventional/surgical treatment to a comprehensive combination of targeted therapy, immunotherapy and other systemic treatments combined with traditional local treatments.
Treatment mode
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Among them, immunotherapy, represented by PD-1 inhibitors, is synergistic when used in combination with anti-angiogenesis drugs that target VEGF.
Blocking VEGF can significantly reduce its immunosuppressive effect, thereby helping anti-tumor activated by immunotherapy Therefore, the two types of drugs are used together for liver cancer, which is expected to overcome the limitations of the respective monotherapy
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Existing clinical studies have shown that the combination of immunization and anti-angiogenesis therapy can bring survival benefits to patients with advanced liver cancer, and innovative drugs independently developed by China are also rapidly advancing in the field of liver cancer.
The Lulizumab+bevacizumab regimen is expected to provide new treatment options for liver cancer patients in China
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Both the first-line and the second-line show the therapeutic value, and the curative effect of the slulizumab + bevacizumab regimen is clear.
The study is divided into four groups.
Groups A, B, and C plan to enroll 60 patients with treated liver cancer who will receive 3 mg/kg slulimumab (once every two weeks/Q2W) in combination with 5 mg/kg HLX04 (n=20), 3 mg/kg slulimumab Q2W combined with 10 mg/kg HLX04 (n=20), or 3 mg/kg slulimumab monotherapy (n=20) while group D program, 60 patients with previously untreated patients, the use of combination therapy and dose are the same as group B
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The study evaluated the treatment effect after two tumor evaluations in all patients.
The main endpoint of the study was the objective response rate (ORR) assessed by the Independent Review Committee (IRRC) according to the RECIST v1.
1 standard
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As of August 4, 2021, a total of 123 patients with advanced liver cancer were included in the study
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Due to the short follow-up time of group C, the CSCO annual meeting disclosed the results of the study of 102 patients in groups A, B, and D who received combined treatment
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From the perspective of patient baseline characteristics, the proportions of patients with an ECOG score of 1 in groups A, B, and D were 35.
0%, 38.
1%, and 41.
0%, respectively, except for one patient in group B with Child-Pugh liver function grade B , The remaining patients are all grade A; the proportion of patients with liver cancer stage C in Barcelona is 90.
0%, 95.
2% and 82.
0%; the proportion of patients with alpha-fetoprotein >400ng/mL is 80.
0%, 61.
9% and 44.
3%, respectively; virological examination The vast majority of patients were infected with hepatitis B, only 1 case in group A and 3 cases in group C had hepatitis C infection; the proportions of distant metastasis and/or large vessel invasion were 90.
0%, 81.
0% and 70.
5%, respectively; A, B, D three cases The proportions of patients in group A and B who had undergone hepatectomy/TACE were 80.
0%/70.
0%, 52.
4%/85.
7%, 47.
5%/50.
8%, respectively.
90.
0% and 95.
2% of patients in groups A and B had received sorafil.
However, there are a small number of patients who have received other treatments such as lenvatinib and chemotherapy
.

When combined therapy was used in treated patients, the IRRC-assessed ORR of 30% (95% CI: 11.
9-54.
3%), median progression-free survival (PFS) and median overall survival of patients in group A (n=20) The periods (OS) were 2.
2 (95% CI: 1.
4-5.
5) and 11.
6 (95% CI: 6.
4-NE) months, respectively; the ORR of patients in group B (n=21) assessed by IRRC was 14.
3% (95% CI : 3.
0-36.
3%), the median PFS and OS were 3.
5 (95% CI: 1.
4-10.
5) and 14.
3 (95% CI: 8.
2-NE) months, respectively
.

When combined therapy was used in group D (n=61), i.
e.
newly treated patients, the ORR assessed by IRRC was 26.
2% (95% CI: 15.
8-39.
1%), and the median PFS and OS were 5.
5 (95% CI: 2.
8-NE) and NE (95% CI: NE-NE) months
.

In terms of treatment safety, the incidence of grade 3 and above TEAEs in groups A, B, and D (n=102) was 44.
1%, and the overall safety of slulimumab combined with bevacizumab was controllable
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From the data of the three combination treatment groups studied, the ORR and other efficacy indicators of the first-line treatment of slulimumab combined with bevacizumab are comparable to the data of other immunotherapeutic drugs combined with bevacizumab; VEGF monoclonal antibody shows better remission rate and survival benefit
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Based on the data of multiple key efficacy indicators such as ORR, PFS, OS, etc.
, the benefit of first-line application of slulimumab combined with bevacizumab is more significant than that of second-line application.
Therefore, it should be considered for patients with advanced liver cancer at the time of diagnosis.
The prerequisite for the application of the combined immunization program, in order to bring more patient benefits
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Comparing group A and group B, the doses of bevacizumab are different.
Group B, namely 3 mg/kg slulizumab Q2W combined with 10 mg/kg bevacizumab, has more significant benefits for PFS and OS.
This may provide hints for the subsequent exploration of this program in liver cancer
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Set sail, the curative effect and safety of the treatment strategy of slulimumab combined with bevacizumab in the treatment of patients with advanced liver cancer have been preliminary verified in the future
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In the future, a wider patient population can be included to analyze the benefits of different subgroups
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Combining with clinical reality, on the basis of this joint plan, the triple treatment plan for advanced liver cancer with local treatments such as intervention and ablation is added to carry out related explorations, striving for better tumor shrinking effect and conversion therapy value, and even expanding the application to early and mid-term operable patients The postoperative adjuvant treatment to reduce recurrence is also worthy of active exploration
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We look forward to more evidence-based medical evidence and research on this program, which will bring more treatment options for Chinese liver cancer patients
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*This article is only used to provide scientific information to medical professionals, and does not represent the views of this platform