Today, Merck announced that its PD-1 inhibitor pembrolizumab (KEYTRUDA) has been approved by the National Medical Products Administration (NMPA) of China for the first-line treatment of patients with locally advanced or metastatic biliary tract cancer (BTC) in combination with gemcitabine and cisplatin. The approval of this new indication is based on data from the global Phase III clinical trial KEYNOTE-966.
"We are pleased to see that driven by the full implementation of the Healthy China 2030 Strategy, the review and approval process of innovative drugs continues to accelerate, especially in terms of access to new drugs that are urgently needed in clinical practice," said Anna Tian, Senior Vice President and President of Merck & Co., Ltd. "In recent years, the incidence of biliary tract malignancies has been on the rise[1], and treatment options for patients with advanced disease are limited[2]. As a leader in oncology treatment, we are committed to covering more malignancies with high morbidity and mortality, low overall survival, and difficult treatment, and bringing more innovative treatment options to cancer patients faster." ”
Biliary tract malignancy is a malignant tumor originating from bile duct epithelial cells, which is characterized by difficulty in early diagnosis, low radical resection rate, and high recurrence rate [3]. Biliary tract cancers mainly include gallbladder cancer and extrahepatic and extrahepatic cholangiocarcinoma [4]. Among them, intrahepatic cholangiocarcinoma is the second largest primary liver cancer after hepatocellular carcinoma, accounting for about 10%~15% of primary liver cancer[5].
"Biliary tract cancer is a highly aggressive tumor [6]. Due to the insidious onset, the early symptoms are subtle and atypical, and the progression is rapid, and most patients with biliary tract cancer have reached an advanced stage at the time of diagnosis [3]. Regrettably, patients with advanced disease are faced with limited treatment options [2], with a five-year survival rate of less than 5%[4], and new treatments and drugs are urgently needed to seek breakthroughs," said Professor Qin Shukui, the principal investigator of the KEYNOTE-966 study in China and Nanjing Tianyinshan Hospital affiliated to China Pharmaceutical University. ”
"Patients with advanced biliary tract cancer often face a poor prognosis[2], and patients with advanced biliary tract cancer at the time of diagnosis have a survival time of less than 1 year[1]," said Dr. Zhengqing Li, Senior Vice President and President of Merck's China R&D Center. ”
The KEYNOTE-966 study[7] is a randomized, double-blind, placebo-controlled, international, multicenter Phase III clinical study evaluating the efficacy and safety of the PD-1 immune checkpoint inhibitor pembrolizumab in combination with gemcitabine and cisplatin (GC) chemotherapy versus GC in the first-line treatment of patients with advanced or unresectable biliary tract cancer. The results showed that pembrolizumab plus GC significantly improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone.
In the KEYNOTE-966 study, a total of 158 Chinese patients were enrolled, and subgroup analysis showed that the Chinese population trial group had better absolute values of efficacy data such as median OS (14.1 months vs 12.7 months), objective response rate (ORR) (36.0% vs 28.9%), and median duration of response (DoR) (10.2 months vs 9.7 months) than the global population, and the absolute value difference was greater than that of the control group.
In addition, the results of the health-related quality of life (HRQol) analysis of the KEYNOTE-966 study, presented at the 2023 ASCO Congress[9], showed that the QLQ-30 global health status/QoL, physical function and role function, The QLQ-BIL-21 jaundice and pain and the least squares mean scores of the EQ-5D-5L visual analogue scale were similar, as was the time to worsening between the two groups, supporting pembrolizumab plus GC as a new first-line treatment option for advanced biliary tract cancer.
So far, pembrolizumab has been approved for 13 indications in China, covering the treatment of melanoma, lung cancer, esophageal cancer, colorectal cancer, head and neck cancer, gastric cancer, liver cancer, breast cancer, biliary tract cancer and MSI-H solid tumors.
References: (Swipe up to view)
[1] Chinese Anti-Cancer Association Biliary Tract Tumor Professional Committee.Chinese Anti-Cancer Association Biliary Tract Malignant Tumor Targeting and Immunotherapy Guidelines (2022)(Short Version)[J].Chinese Journal of Practical Surgery, 2023,43(5):481-491.DOI:10.19538/j.cjps.issn1005-2208.2023.05.01.
[2] Xie C, McGrath NA, Monge Bonilla C, Fu J. Systemic treatment options for advanced biliary tract carcinoma. J Gastroenterol. 2020 Oct; 55(10):944-957. doi: 10.1007/s00535-020-01712-9. Epub 2020 Aug 3. PMID: 32748173; PMCID: PMC7519922.
[3] Zhang Zhengfeng, Yang Lei, Wang Dazhen, Lou Changjie.Current status and progress in the treatment of locally advanced or advanced biliary tract malignant tumors[J].China Oncology,2022,31(7):569-577.DOI:10.11735/j.issn.1004-0242.2022.07.A009.
[4] Chinese Society of Clinical Oncology. CSCO Guidelines for the Diagnosis and Treatment of Biliary Tract Malignancies (2023 Edition)
[5] Cholangiocarcinoma Collaboration Group, Liver Cancer Professional Committee, Chinese Anti-Cancer Association. Guidelines for the diagnosis and treatment of primary liver cancer: Chinese expert consensus on the diagnosis and treatment of intrahepatic cholangiocarcinoma (2022 edition) [J] . Chinese Journal of Digestive Surgery, 2022, 21(10) : 1269-1301. DOI: 10.3760/cma.j.cn115610-20220829-00476.
[6] Vogel A, Saborowski A. Current and Future Systemic Therapies in Biliary Tract Cancer. Visc Med. 2021 Feb; 37(1):32-38. doi: 10.1159/000513969. Epub 2021 Jan 6. PMID: 33708816; PMCID: PMC7923904.
[7] Robin KK,et.al.pombrolizumab in combination with gemcitabine and cisplatin compared with gemcitabine and cisplatin alone for patients with advanced biliary tract cancer（KEYNOTE-966）:a randomised,double-blind,placebo-controlled,phase 3 trial. Lancet 2023；401：1853-65.published online April 16,2023.https：doi.org/10.1016/S0140-6736（23）00727-4
[8] https://www.clinicaltrials.gov/study/NCT04924062?term=keynote-966&rank=2&tab=results
[9] Changhoon Y, et al. Health-related quality of life(HRQoL) in the phase 3 KEYNOTE-966 study of pembroizumab (pembro) plus gemcitabine and cisplatin(gem/cis) versus placebo plus gem/cis for advanced biliary tract cancer (BTC). 2023ASCO, abstr.4003.
审校:Uni
Typography: Uni
Execution: Uni
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.