2021 AACR | PI Interview: Professor Li Gaofeng's wonderful comment on tislelizumab RATIONALE 303 research, Chinese wisdom shines on the international stage!

*It is only for medical professionals to read for reference.
Tilelizumab breaks the dilemma of the second/third-line treatment of advanced NSCLC and benefits the whole population.

In 2021, the American Association for Cancer Research (AACR) announced the results of the breakthrough study RATIONALE 303 clinical trial of tislelizumab in the field of lung cancer.
Compared with chemotherapy, tislelizumab alone can significantly improve the second/third-line non- The overall survival of patients with small cell lung cancer (NSCLC), and the safety is good.

This is another breakthrough of tislelizumab in the treatment of advanced NSCLC following the success of RATIONALE 307 (first-line combination therapy for advanced squamous NSCLC) and RATIONALE 304 (first-line combination therapy for advanced non-squamous NSCLC).

To this end, the "medical community" specially invited one of the main researchers of the clinical research, Professor Li Gaofeng from Yunnan Cancer Hospital to interpret and share the research results in depth.

In the immune era, the second and third-line treatment of advanced NSCLC is still not optimistic.
With the advancement of technology, there are more and more treatment methods for lung cancer, and the treatment model has also developed from traditional surgery and radiotherapy/chemotherapy to targeted and immunotherapy.

Immunotherapy has brought revolutionary changes to the treatment of advanced NSCLC patients with negative driver genes.
The 5-year survival rate of patients has been significantly improved, and many patients have obtained long-term benefits after using immunotherapy.

At present, my country has approved a series of PD-1/PD-L1 monoclonal antibodies including tislelizumab for the first-line treatment of various types of NSCLC.
For the immunotherapy of second-line NSCLC, only nivolumab has been approved.
, Patient options are relatively limited, and more diversified treatment options are urgently needed in clinical practice.Professor Li Gaofeng said: “Although immunotherapy has good efficacy, in clinical practice in China, there are still a large number of patients with advanced lung cancer who have not received immunotherapy in the first line.
The current domestic second-line treatment strategy is mainly docetaxel.
Chemotherapeutics are the main drugs, and the effective rate of single drugs is low.
The median survival time of patients is only about 10 months, and the clinical benefit is limited.

In fact, after the first-line treatment of some advanced NSCLC patients fails, if they can receive immunotherapy in time and effectively Greatly prolong the median survival time.

"Data is king, tislelizumab brings revolutionary benefits.
Facing the dilemma of second/third-line treatment options and efficacy in advanced NSCLC, China’s independent research and development of innovative immunotherapy drug tislelizumab The monoclonal antibody brought a breakthrough.

The RATIONALE 303 study published by the AACR meeting in the United States in 2021 showed that compared with the docetaxel treatment group, the risk of death in the tislelizumab group was reduced by 36%, and the median overall survival (OS) was extended by nearly half a year (17.
2 months vs.
11.
9 months); the 2-year OS rate reached 1.
6 times that of the chemotherapy group (39.
4% vs.
25.
0%), which has a clear advantage over previous data from similar clinical studies.

 Figure 1.
The overall survival of the ITT population and, regardless of the expression of PD-L1, patients can benefit: For patients with PD-L1 ≥ 1%, tislelizumab can reduce the risk of death by 42%, PD-L1 The risk of death in patients less than 1% can also be reduced by 26%.

Table 1.
OS subgroup analysis In terms of efficacy, the objective response rate of patients in the tislelizumab treatment group was increased by more than 3 times compared with chemotherapy (21.
9% vs.
7.
0%), and the median duration of response was increased to twice that of the chemotherapy group Above (13.
5 months vs.
6.
2 months).

It is worth noting that the incidence of adverse reactions in the tislelizumab group is generally lower than that in the chemotherapy group, although the treatment cycle of patients is more than twice that of the chemotherapy group (9.
4 cycles vs.
4.
5 cycles), and immune-related adverse reactions occur The rate is low, and the incidence of treatment-related adverse reactions above grade 3 is only 14%, which is significantly lower than the 66% in the chemotherapy group.

Professor Li Gaofeng said: “As a doctor, clinical treatment decisions must comply with three principles, namely, safety, effectiveness and accessibility.

The results of the RATIONALE 303 study fully meet these three principles.
The success of the study provides good evidence-based medicine evidence for the choice of drugs for late-stage clinical NSCLC.

"According to the results of the RATIONALE 303 study, tislelizumab's second/third-line monotherapy for the treatment of non-small cell lung cancer has been accepted by the National Medical Products Administration (NMPA).
select the lack of status of patients with NSCLC two / third-line treatment, improve the current treatment pattern, the overall benefit of the general NSCLC patients.

tracing the source for basic research Reilly natalizumab winning thousands of miles away is well known that the drug has a different structure differences.

phase Compared with similar immune checkpoint inhibitors, tislelizumab can achieve superior performance mainly due to its unique structural design.

On the one hand, tislelizumab has undergone Fc segment modification, which can effectively avoid antibody-dependent cells Toxic effect (ADCP), minimize the binding of FcγR to macrophages, and retain the number and function of effector T cells to the greatest extent.

On the other hand, tislelizumab has a unique binding epitope, which is on PD-1 The binding surface overlaps with PD-L1 in a large range, completely blocking the binding of PD-1 and PD-L1.

The more the drug binds to the PD-1 of tumor cells, the better the tumor-killing effect.

 Professor Li Gaofeng said "The effective rate and objective remission rate of patients enrolled in our research center for tislelizumab treatment performed well.
More importantly, when used for third-line treatment, the safety of tislelizumab is particularly outstanding.

I once diagnosed and treated a patient with stage IV NSCLC with multiple lymph node metastases in both lungs.
The patient was 65 years old at the time of diagnosis and received second-line standard treatment in a foreign hospital, but the tolerance was poor and the willingness to treat was low.

In the face of the patient’s old age and no medicines available, we tried to give him tislelizumab treatment.
After several cycles of treatment, the patient achieved partial remission (PR), and both lung metastases and lymph nodes were well controlled.
The medication was continued for 9 months, and there were almost no adverse reactions during the treatment period, and the quality of life was also greatly improved. "Professor Li Gaofeng pointed out: "Previous domestic studies of PD-1 in lung cancer have used PFS as the main research endpoint, and OS is the gold standard for measuring the efficacy of tumor drugs.

The RATIONALE 303 study took OS as the primary endpoint and was successful, breaking the current limitations of medical inefficiency after the failure of the first and second-line treatments for advanced NSCLC patients, and truly achieving longer survival and more benefits.

It is expected to promote the changes in the guidelines and benefit more patients with advanced lung cancer in China! "Tilelizumab is a PD-1 monoclonal antibody independently developed by BeiGene.
It has been approved by the NMPA for combined chemotherapy for the first-line treatment of advanced squamous NSCLC.
It is combined with chemotherapy for the first-line treatment of non-squamous NSCLC and the second-line single-agent treatment /The new indication application for third-line advanced NSCLC has been accepted by NMPA and approved.

In the recently updated "CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines (2021 Edition)", tislelizumab combined with chemotherapy is the first-line treatment Advanced squamous NSCLC was recommended by the guideline level I, combined with chemotherapy for first-line treatment of advanced non-squamous NSCLC with negative driver gene, and single-agent second/third-line treatment for advanced NSCLC were also recommended by the guideline based on class IA evidence.

Tislelizumab became the first In the first and second-line immunotherapy of advanced NSCLC, it has been fully recommended by the guidelines for domestic independent research and development of PD-1 monoclonal antibodies.

References: [1]Caicun Zhou, et al.
Results from RATIONALE 303: A global Phase 3 study of tislelizumab vs docetaxel as second- or third-line therapy for patients with locally advanced or metastatic NSCLC.
2021 AACR.
[2]《 CSCO Immune Checkpoint Inhibitors Clinical Application Guidelines (2021 Edition)" Expert Profile Professor Li Gaofeng Second-level Professor, Chief Physician Doctoral Tutor, Post-Doctoral Cooperative Tutor Yunnan Provincial Tumor Hospital, Kunming Medical University Third Affiliated Hospital Deputy Dean National Excellent Science and Technology Work An expert who enjoys special allowances from the provincial government.
Excellent professional and technical personnel with outstanding contributions in Yunnan Province, a famous Yunling doctor, a leading medical talent in Yunnan Province, a provincial party committee contact expert, a famous teaching teacher, a member of the International Association for Lung Cancer Research, a standing committee member of the Mediastinal Tumor Professional Committee of the Chinese Anti-Cancer Association Member of the Thoracoscopy Surgery Group of the Thoracic and Cardiovascular Surgery Branch of the Medical Association Member of the National Lung Cancer MDT Expert Committee Chairman of the Yunnan Translational Medicine Society Vice Chairman of the Yunnan Anti-Cancer Association Vice Chairman of the Yunnan Anti-Cancer Association Director of the Professional Committee of Minimally Invasive Thoracic Tumor Therapy Yunnan Executive Director of the Provincial Preventive Medicine Association and Chairman of the Lung Cancer Professional Committee Deputy Chairman of the Thoracic and Cardiovascular Surgery Branch of the Yunnan Medical Association