The Hope of Lai Su|Professor Bai Yuxian: National medicine shines in ASCO, adding a new weapon in the field of biliary tumors

*Only for medical professionals to read and reference.
Focus on ASCO and appreciate the latest developments in Chinese research in the field of biliary tumor treatment.

The 2021 American Society of Clinical Oncology (ASCO) annual meeting will be held from June 4 to June 8.
The single-arm, multi-center, open-label phase II clinical trial of Sofantinib for patients with unresectable or metastatic biliary tract cancer (BTC) made a stunning appearance at this conference (Abstract No.
e16123) [1].
The surufatinib group (surufatinib) has good survival benefits and good safety, providing a new treatment option for patients with advanced biliary tumors.

The "medical community" specially invited Professor Bai Yuxian to give a wonderful interpretation of this research and talk about the future treatment direction in the field of biliary tumors.

Study Design The criteria for enrollment of patients in this study were: age ≥18 years; unresectable or metastatic advanced BTC confirmed by histology or cytology, including extrahepatic cholangiocarcinoma (ECC), intrahepatic cholangiocarcinoma (ICC) or Gallbladder cancer (GBC); patients who have failed or become intolerable after receiving first-line cytotoxic chemotherapeutics; Eastern Cooperative Oncology Group (ECOG) performance status score 0-1, and must have measurable lesions.

Sofatinib single-agent second-line treatment dose is 300 mg, once a day, every 28 days as a cycle.

According to the RECIST version 1.
1, tumor evaluation is performed every 8 weeks ± 7 days.

The primary endpoint is the 16-week disease progression-free survival rate (16-week PFS%), and the secondary endpoints are overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) , Duration of mitigation (DoR), safety, etc.

The results of the study as of November 30, 2018, the study included 39 BTC patients receiving sofatinib treatment, of which 29 cases (74.
4%) were ICC, 5 cases (12.
8%) were ECC, and 5 cases (12.
8%) For GBC.

Primary endpoint: The 16-week PFS rate was 46.
33% (95% CI 24.
38-65.
73), and the secondary endpoint: median PFS was 3.
7 months, and median OS was 6.
9 months.

In terms of safety: the first three treatment-related adverse events (TRAEs) with the highest severity and severity of grade 3 include elevated blood bilirubin (20.
5%), hypertension (17.
9%), and proteinuria (12.
8%).

In addition, the results of subgroups and post-mortem analysis showed that patients with intrahepatic tumors or patients with low baseline levels of CA19-9 (≤1000 IU/ml) and CEA (≤3ng/ml) had better clinical benefits.

Research summary The overall efficacy data of Sofatinib is similar to other vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI), which also has clinical efficacy and good safety.

Based on this, the future can be explored in the joint direction.

Expert Profile Professor Bai Yuxian, Chief Physician, Department of Digestive Oncology, Harbin Medical University Tumor Hospital, Executive Director, Chinese Society of Clinical Oncology, Deputy Chairman, Liver Cancer Expert Committee, Chinese Society of Clinical Oncology, Deputy Chairman, Vascular Targeting Expert Committee, Chinese Society of Clinical Oncology, Heilongjiang Medical Association Chemotherapy Major Committee Chairman, Heilongjiang Anticancer Association Chemotherapy Specialty Committee Chairman, Heilongjiang Targeted Therapy Specialty Committee of China Bioengineering, the rise of targeted immunity, biliary tumors usher in the dawn▌"Medical industry": You have been deeply involved in gastrointestinal tumors for many years Could you please talk about the current status of the treatment of biliary tract tumors? Professor Bai Yuxian: Biliary tract tumors are highly heterogeneous and highly malignant tumors.

According to the different location of the disease, it can be divided into three types: intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma and gallbladder cancer.

Usually the early symptoms are not obvious, so most patients are diagnosed in the late stage, and the prognosis is poor.
The 5-year survival rate of advanced patients is less than 5%.

The first-line treatment plan for advanced BTC is cisplatin combined with gemcitabine (GP), but the survival benefit is limited, the median OS is no more than 1 year, and there is no standard treatment plan for patients after progression.

In addition, the incidence of biliary tract tumors is also increasing year by year, and the field of biliary tract tumors is facing a huge and unmet clinical treatment demand.

In recent years, with the continuous emergence of new theories, new technologies, new methods and new hot spots, biliary tract tumors are gradually being broken.

Among them, targeted drugs and immune drugs are particularly prominent.
For example, targeted combined immunization and chemotherapy combined immunization have been explored in the field of biliary tumors.
At present, we have also seen good effects in clinical practice.
These emerging drugs are expected to give BTC patients Treatment brings new hope and light.

With the strength of ASCO, Sofatinib can be expected in the future▌"Medical industry": The research you participated in was made a stunning appearance at this year's ASCO conference.
Combining relevant results to talk about the highlights of the research? Professor Bai Yuxian: The study announced at this conference aims to evaluate the efficacy and safety of sofantinib as a single-agent second-line treatment of BTC patients.
The study included patients who had failed standard first-line chemotherapy.
The results of the study showed that, The patient's survival benefit was obvious, with a median OS of 6.
9 months and a median PFS of 3.
7 months, confirming that the efficacy of Sofatinib as a single agent is similar to that of similar VEGFR-TKI drugs and has clinical value.

And in terms of safety, sofatinib is better tolerated.
The main adverse reactions are hypertension and proteinuria, and no hand-foot skin reactions.

For patients with advanced biliary tract tumors, the physical status of the patients is average, and the lower incidence of adverse reactions can improve the patient's medication compliance, and bring greater protection to their efficacy and quality of life.

Therefore, Sofatinib is expected to become an important treatment option for patients with biliary tumors.

In addition, based on the efficacy and safety of sofatinib as a single agent, it also gives us confidence to explore combined immunization or chemotherapy on the basis of a single agent.

The hope of coming to the Soviet Union shows the strength of local originality▌"Medical industry": As a new small molecule targeted drug independently developed by my country, please talk about the advantages of Sofatinib compared with similar VEGFR-TKI drugs ? Professor Bai Yuxian: Sofatinib is a representative multi-target inhibitor, first of all its mechanism of action is different from other VEGFR-TKIs on the market: Sofatinib can selectively inhibit VEGFR-1/2/3 , FGFR-1 achieves the effect of anti-angiogenesis, and also has the effect of blocking the CSF-1R target to improve tumor immunosuppression.

Studies have confirmed that it inhibits CSF-1R, regulates TAM, and increases CD8+T cell infiltration, which can activate the body's immune response to tumor cells and achieve 1+1+1＞＞3 synergistic effects of combined immunotherapy.

As we all know, currently targeted or immune single drugs have limited efficacy, and combination is the future trend of exploration, so Sofatinib has certain advantages in combined applications.

Secondly, in terms of safety: the main adverse reactions are hypertension, proteinuria, and no hand-foot skin reactions.

Whether it is a single drug or a combination drug, it has the characteristics of low toxicity, high efficiency, and good patient compliance.

Finally, it is worth mentioning that Sofantinib, as a “native-born” domestically produced innovative drug, is based on the local market and does not forget its original intention.
Its affordable price and charitable assistance policy will enable more patients with biliary tract tumors to receive treatment protection.
Burn the hope of survival for patients.

More exploration, combination therapy may become the future direction▌"Medical community": Could you please talk about the future exploration direction of Sofatinib in the field of biliary tumors? Professor Bai Yuxian: Past studies have shown that monotherapy has limited efficacy in biliary tumors.

Combination therapy is widely used and explored in clinical practice.
For example, the "cola" combination composed of lenvatinib and pembrolizumab, which is currently used more clinically, is shown according to the data released by 2021ASCO [2], this combination plan is a second-line treatment In patients with advanced (metastatic and/or unresectable) BTC, ORR was 10%, DCR was 68%, median PFS was 6.
1 months, and median OS was 8.
6 months.
The overall efficacy is better than that of targeted or immune single drugs.
A great breakthrough.

Similarly, the "triple four-drug" program (lenvatinib + teriprizumab + oxaliplatin + gemcitabine) developed by the team of Academician Fan Jia and Professor Zhou Jian from Zhongshan Hospital of Fudan University has achieved better results in the treatment of advanced ICC.
Significant clinical benefit.
The latest data from 2021ASCO [3] show that its ORR is as high as 80%, and its DCR is as high as 93.
3%.
The study’s encouraging efficacy and manageable toxicity suggest that our targeted-based combination is the future of the biliary tract.
Favorable direction in the field of tumor treatment.

In the exploration direction of combination therapy, the clinical application of sofatinib has broad prospects.

First of all, the current phase I study of sofatinib combined with teriprizumab in the treatment of advanced solid tumors [4] has achieved breakthrough results.
Its DCR is as high as 79.
3%, ORR is as high as 34.
5%, and the DCR in the 250mg group is as high as 100.
%, ORR is as high as 63.
6%, which greatly reflects that sofatinib combined with immunotherapy has a definite effect on multiple tumor types.

The phase II clinical study of sofatinib combined with teriprizumab for the treatment of advanced solid tumors is also in full swing, including patients with advanced biliary tract cancer, which will effectively verify the importance of sofatinib combined immunity in the field of biliary tumors Application value, results are worth looking forward to.

Secondly, as just introduced, the synergistic mechanism of sofatinib anti-angiogenesis + anti-TAM cell combined immunotherapy, combined with immune checkpoint drugs, has a synergistic effect of 1+1+1>>3.

I look forward to seeing Sofatinib make greater breakthroughs in the field of biliary tract in the future, bringing more benefits to patients with biliary tract tumors, and I also look forward to Sofatinib being widely used in the treatment of a variety of gastrointestinal tumors, and through a variety of application strategies.
(Synergy immunotherapy/chemotherapy/interventional therapy, etc.
) to exert its effect
Reference materials: [1] Bai YX, Xu JM, Sun HC, et al.
A single-arm,multicenter, open-label phase 2 trial of surufatinib in patients with unresectable or metastatic biliary tract cancer.
2021 ASCO.
e16123.
https:/ /meetinglibrary.
asco.
org/record/199625/abstract.
[2] Luis Villanueva L, et al.
Lenvatinibplus pembrolizumab for patients with previously treated biliary tract cancersin the multicohort phase 2 LEAP-005 study.
2021ASCO.
4080[3] Zhou J , et al.
Gemoxchemotherapy in combination with anti-PD1 antibody toripalimab and lenvatinibas first-line treatment for advanced intrahepaticcholangiocarcinoma: A phase 2 clinicaltrial.
2020ASCO.
4094.
[4]Lu M, Cao YS, Gong JF,et al.
A Phase I Trial of Surufatinib plus Toripalimab inPatients with Advanced Solid Tumor.
AACR 2020.
Abstract No.
9563.
*This article is only used to provide scientific information to medical professionals and does not represent the views of this platform