//
On the journey of fighting lung cancer, immunotherapy is like a dawn of dawn, bringing unprecedented hope for patients to survive. Not long ago, as the leader of the original PD-(L)1 monoclonal antibody in China, tislelizumab (tislelizumab, TEVIMBRA) has made another major breakthrough: the European Commission (EC) officially approved tislelizumab for three indications for the first-line and second-line and above treatment of non-small cell lung cancer (NSCLC)1, making tislelizumab the first and only PD-(L)1 inhibitor independently developed in China for the indications of NSCLC approved overseas. At the same time, the indication of tislelizumab in combination with etoposide and platinum-based chemotherapy for the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) has also been approved by the National Medical Products Administration (NMPA) of China, bringing a new option of immunotherapy to the majority of SCLC patients.
On this occasion, we are honored to invite Professor Wang Zhiyu from the Fourth Hospital of Hebei Medical University to interpret and comment on the specific content and significance of this approval and the latest progress of tislelizumab in the field of small cell lung cancer from his professional perspective.
- Prof. Zhiyu Wang -
- Director of the Department of Tumor Immunology, Chief Physician and Doctoral Supervisor of the Fourth Hospital of Hebei Medical University
- Deputy Director of the Stem Cell and Immune Cell Research Center, Institute of Medicine and Health, Hebei Medical University
- Deputy Director of the Scientific Research Department of the Fourth Hospital of Hebei Medical University
- Young Director of the Oncology Branch of the Chinese Medical Association
- Chairman of the Tumor Biotherapy Professional Committee of Hebei Anti-Cancer Association
- Chairman of the Tumor Biotherapy Professional Committee of Hebei Immunology Society
- Secretary-General of the Physician Branch of Hebei European and American Scholars Association
- Member of the Standing Committee of the Medical Oncology Committee of Hebei Anti-Cancer Association
- Secretary of the Oncologist Branch of Hebei Medical Doctor Association
- Executive Director of Hebei Immunology Society
- Member of Chinese Society of Immunization
With full coverage, tislelizumab won the European Union with three NSCLC indications
Professor Wang Zhiyu proudly reviewed the "going overseas" process of tislelizumab. In September 2023, tislelizumab crossed the country for the first time, and its excellence in the global multicenter, phase III RATIONALE-302 study was recognized by the EC, and the indication of tislelizumab for the treatment of unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) previously treated with platinum-containing chemotherapy was officially approved in Europe, and then it was approved by the United States Food and Drug Administration (FDA) in March 2024. This is the second approval of tislelizumab in the European Union after the indication of esophageal cancer, and it is also the only domestic PD-(L)1 inhibitor approved for NSCLC indication overseas.
According to Professor Wang Zhiyu, the approval is based on the results of three major studies of tislelizumab in advanced NSCLC, including the RATIONALE-307 study (advanced first-line lung squamous cell carcinoma)2, the RATIONALE-304 study (advanced first-line non-squamous cell carcinoma)3 and the RATIONALE-303 study (treated NSCLC)4. These three studies included a total of 1,499 patients and provided strong evidence-based evidence for the use of tislelizumab in NSCLC.
For first-line treatment of advanced lung squamous cell carcinoma, tislelizumab demonstrated a high objective response rate (ORR) comparable to targeted therapy. In the RATIONALE-307 study2, tislelizumab showed a response rate of 74% and a median progression-free survival (mPFS) of 9.6 months, significantly reducing the risk of disease progression by 57% compared with chemotherapy alone. The median overall survival (mOS) was 26.1 months, and the risk of death was reduced by 47%, bringing long-term survival benefits to patients with advanced lung squamous cell carcinoma. For first-line treatment of advanced non-squamous NSCLC, the RATIONALE-304 study3 showed that tislelizumab in combination with chemotherapy significantly blocked disease progression, with mPFS of 9.8 months and a significant 37% reduction in the risk of disease progression; mOS for 21.6 months significantly reduced the risk of death by 32%. It is worth mentioning that more than 40% of the patients enrolled in the RATIONALE-304 study had PD-L1 expression <1%, and more than 35% of the patients had distant metastases. Compared with similar studies, the baseline enrollment of the RATIONALE-304 study is more challenging, but it is also closer to the real clinical practice, which can more clearly guide clinical medication. For advanced treatment-experienced NSCLC, the RATIONALE-303 study4 showed excellent efficacy of tislelizumab treatment, with mOS of 16.9 months, mPFS of 4.2 months, ORR of 23%, and no restriction on PD-L1 expression.
Professor Wang Zhiyu believes that the approval of tislelizumab in the EU is of great significance in many aspects. First of all, from the perspective of the globalization of innovative drugs in mainland China, tislelizumab can successfully enter the EU market in the field of large tumors, demonstrating the international competitiveness of China's pharmaceutical industry and proving to the world that China has the ability to develop innovative drugs with international standards. This undoubtedly marks the improvement of the recognition and competitiveness of China's innovative drugs in the world, and will encourage more Chinese pharmaceutical companies to increase R&D investment, promote more innovative drugs to the international market, and further promote the cooperation and exchange of global drug research and development. Secondly, this approval also provides more treatment options for lung cancer patients around the world, especially in Europe. It is reported that tislelizumab has also submitted applications for other indications in the EMA and FDA, covering the first-line treatment of unresectable locally advanced, recurrent or metastatic ESCC, as well as the first-line treatment of gastric or gastroesophageal junction adenocarcinoma.
Standing at the forefront of the tide and making endless progress, tislelizumab leads a new era of long-term survival in SCLC immunotherapy
Tislelizumab has not only made significant achievements in the field of NSCLC, but also made significant progress in the field of SCLC. Recently, the results of a phase III RATIONALE-312 study of tislelizumab in combination with chemotherapy for the first-line treatment of ES-SCLC were published in the Journal of Thoracic Oncology. Based on the success of this study, tislelizumab was recently approved for a new indication in combination with etoposide and platinum-based chemotherapy for the first-line treatment of ES-SCLC.
Professor Wang Zhiyu introduced that this is a phase III randomized controlled trial of tislelizumab combined with standard chemotherapy and placebo combined with standard chemotherapy in the first-line treatment of ES-SCLC patients, with the primary endpoint of OS and the secondary endpoints including PFS, ORR, duration of response (DoR) and safety 5. The study was initiated in July 2019 and included a total of 457 patients with a median follow-up of 14.2 months. Results from the RATIONALE-312 study showed that the mOS of tislelizumab plus chemotherapy was 15.5 months, resulting in a significant survival benefit for ES-SCLC patients. What's even more gratifying is that the 3-year OS rate has reached a breakthrough of 25% (control group: 9%), in other words, 1/4 of ES-SCLC patients have a survival time of more than 3 years, which is a new survival record in the current first-line treatment of ES-SCLC phase III study by immunotherapy combined with chemotherapy, and is expected to truly achieve long-term survival of ES-SCLC patients. At the same time, the mPFS of tislelizumab plus chemotherapy was 4.8 months, which significantly reduced the risk of disease progression by 37%. The one-year PFS rate was 21 percent, or more than one-fifth of patients with SCLC achieved progression-free disease within one year, four times that of the control group (5 percent of the control group). At the same time, the confirmed ORR was 68%, and nearly 70% of patients could benefit from tislelizumab + chemotherapy, a significant improvement compared to the control group5.
Professor Wang Zhiyu said that although several PD-(L)1 inhibitors have been approved for the treatment of ES-SCLC in China, no drugs have been included in the scope of medical insurance reimbursement. For patients with ES-SCLC, there is an urgent need for immunotherapy regimens that are both effective and affordable. Tislelizumab is affordable, and compared with the high price of previous SCLC immunotherapy, it can effectively reduce the treatment threshold and economic burden of SCLC patients receiving immunotherapy. Professor Wang Zhiyu believes that the success of the RATIONALE-312 study of tislelizumab not only refreshed the survival record of SCLC patients, but also enabled one-quarter of patients to survive for 3 years, leading the long-term survival mode of SCLC immunotherapy. At the same time, the approval of this indication has further improved the accessibility of SCLC immunotherapy drugs, breaking the high-price barrier of immunotherapy for SCLC patients, and enabling SCLC patients to enjoy international quality drugs at affordable prices.
Conclusion
Every step of tislelizumab's "going overseas" is sonorous and powerful, demonstrating the international influence of China's original drugs. The international journey of tislelizumab is a powerful embodiment of China's pharmaceutical innovation strength. We expect that with the emergence of more domestic original drugs, the Voice of China will become louder and louder on the international pharmaceutical stage, and contribute Chinese wisdom and Chinese strength to the health of all mankind.
*As of July 9, 2024
Bibliography:
1. Official website of the European Medicines Agency (EMA): https://www.ema.europa.eu/en%EF%BC%8C.
2.Wang J, et al. Tislelizumab Plus Chemotherapy vs Chemotherapy Alone as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer: A Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 May 1; 7(5):709-717.
3.Lu S, et al. Tislelizumab Plus Chemotherapy as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC (RATIONALE 304): A Randomized Phase 3 Trial. J Thorac Oncol. 2021 Sep; 16(9):1512-1522.
4.Zhou C, et al. Tislelizumab Versus Docetaxel in Patients With Previously Treated Advanced NSCLC (RATIONALE-303): A Phase 3, Open-Label, Randomized Controlled Trial. J Thorac Oncol. 2023 Jan; 18(1):93-105.
5.Cheng Y, et al. Tislelizumab plus platinum and etoposide versus placebo plus platinum and etoposide as first-line treatment for extensive-stage SCLC (RATIONALE-312): a multicenter, double-blind, placebo-controlled, randomized, phase 3 clinical trial. J Thorac Oncol. 2024 Mar 7:S1556-0864(24)00115-1.
Edit: Echo
Reviewer: Echo
Typesetting: KIKI
Executive: Babel
This platform aims to deliver more medical information to healthcare professionals. The content published on this platform should not be used as a substitute for professional medical guidance in any way, nor should it be regarded as diagnosis and treatment advice. If such information is used for purposes other than understanding medical information, the platform does not assume relevant responsibilities. This platform does not mean that it agrees with its descriptions and views on the published content. If copyright issues are involved, please contact us, and we will deal with it as soon as possible.