Durvalumab Approved as First-Line Immunotherapy for Biliary Tract Cancer in China: A Breakthrough Endorsed by Academician Chen Xiaoping

Nov 15, 2023 20:01 CST Updated 20:01

AstraZeneca

Biopharmaceutical Manufacturer

Source: Cancer News

Source: Oncology News

AstraZeneca announced on November 14, 2023, that Imfinzi (English Trade Name: IMFINZI, Generic Name: Durvalumab) has officially received approval from the National Medical Products Administration (NMPA) on November 7 for use in combination with gemcitabine and cisplatin as a first-line treatment for adult patients with locally advanced or metastatic biliary tract cancer (BTC). As the first immunotherapy regimen approved in China specifically for biliary tract cancer, the combination of durvalumab and chemotherapy marks a solid step forward for AstraZeneca in the field of hepato-biliary tumors.

On this important occasion, 【Tumor Information】was specially invitedAcademician Chen Xiaoping of the Chinese Academy of Sciences, extending congratulations on the approval of durvalumab's first-line indication for biliary tract cancer.

Chen Xiaoping

Academician, Chief Physician, Professor, Doctoral Supervisor

Academician of the Chinese Academy of Sciences, Expert in Hepatobiliary Surgery
Director of the Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; Director of the Hepatobiliary and Pancreatic Surgery Research Institute
Systematic and innovative achievements have been made in the surgical treatment of liver cancer and liver transplantation: proposing a new classification of liver cancer and the theory of safe resection of large liver cancers; establishing three techniques for controlling bleeding during hepatectomy and one technique for liver transplantation, which have been applied clinically with significant results.
Has won the Second Prize of the National Science and Technology Progress Award, the Second Prize of the National Teaching Achievement Award, the First Prize of the Ministry of Education's Nomination for the National Science and Technology Progress Award, and other awards.
Successively awarded as a National Teaching Master, Advanced Individual in National Health Units, Middle-aged and Young Expert with Outstanding Contributions by the Ministry of Health, recipient of the National May 1 Labor Medal, and a Role Model of Medical Ethics in China.

Biliary tract cancer is highly malignant, with 70% of patients diagnosed at an advanced stage and a 5-year survival rate of less than 10%.[1]

Biliary tract malignant tumors include gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma, which are a group of highly heterogeneous tumors. Biliary tract cancer is defined as a rare cancer type in most Western countries, including Europe and the United States, but its incidence is relatively higher in Southeast Asian countries (including China), accounting for 3% of gastrointestinal tumors.[2]Biliary tract cancer lacks specific symptoms in the early stage and is highly invasive. Seventy percent of patients are already in the advanced stage when they seek medical attention, losing the opportunity for surgical cure, seriously affecting the life and health of the people in China.

Patients with advanced biliary tract cancer have a total survival of less than one year with standard chemotherapy, urgently awaiting new treatment options.

Advanced biliary tract cancer uses the gemcitabine combined with cisplatin (GC) regimen as the first-line standard chemotherapy, represented by the GC chemotherapy regimen in the ABC-02 study.[3]It is a randomized Phase III clinical study. The results of this study showed that in patients with advanced biliary tract cancer, the median overall survival (mOS) of biliary tract cancer patients receiving the GC regimen was 11.7 months (11.7 months vs 8.1 months;HR=0.64；95%CI，0.52–0.80；p<0.001). The treatment needs of patients with biliary tract cancer are far from being met, and a survival period of less than one year can no longer satisfy patients' pursuit of long-term survival, urgently awaiting new treatment options.

TOPAZ-1 Study Triple-Positive Results Establish New Standard for Advanced Biliary Tract Cancer Treatment, Receive Highest-Level Recommendation from Four Major Authoritative Guidelines Both in China and Internationally

In recent years, with the development and application of systemic therapeutic drugs, immunotherapy, targeted therapy, and combination treatment modalities are gradually transforming the treatment landscape for advanced biliary tract cancer, bringing new hope for further improving efficacy.

At the 2022 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (ASCO-GI), the TOPAZ-1 study was presented.[6]Data.

· TOPAZ-1 Study[4-6]A randomized, double-blind, placebo-controlled, global multi-center Phase III study[4], aiming to explore the efficacy and safety of durvalumab combined with GC chemotherapy compared to placebo combined with GC chemotherapy. The primary endpoint of the study is OS, with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and safety.

· The mOS of the Durvalumab combined with GC chemotherapy group was 12.9 months, which was 1.6 months longer than that of the GC chemotherapy group, and the risk of death was further reduced by 24% (12.9 months vs 11.3 months,HR=0.76; 95% CI, 0.64-0.91); and the two-year OS rate in the durvalumab plus GC chemotherapy group was nearly double that of the GC chemotherapy group (23.6% vs 11.5%);

· The median PFS in the durvalumab plus GC chemotherapy group reached 7.2 months, significantly extending by 1.5 months compared to the GC chemotherapy group (7.2 months vs 5.7 months,HR=0.75；95%CI，0.63–0.89；p=0.001）；

· The ORR of the Durvalumab combined with GC chemotherapy group was better than that of the GC chemotherapy group (26.7% vs 18.7%);

· In terms of safety, compared with the GC chemotherapy group, the addition of durvalumab to GC chemotherapy did not increase the discontinuation rate due to adverse events (AEs); the incidence of grade 3/4 treatment-related adverse events (TRAEs) was 60.9% in the durvalumab plus GC chemotherapy group and 63.5% in the GC chemotherapy group.

Based on the aforementioned TOPAZ-1 study data, in September 2022, the U.S. Food and Drug Administration (FDA) approved this regimen for first-line treatment of locally advanced or metastatic biliary tract cancer. In November of the same year, Europe also approved durvalumab for the treatment of biliary tract cancer. The regimen of durvalumab + chemotherapy simultaneously received Level I or preferred recommendations from the four authoritative guidelines CSCO, NCCN, ESMO, and CACA, with robust evidence from evidence-based medicine.

Academician Chen Xiaoping statedThe TOPAZ-1 study is the first Phase III trial in the field of immunotherapy combination treatment for biliary tract cancer to demonstrate benefits in OS, PFS, and ORR, and is unanimously recommended by guidelines both in and outside China as a first-line treatment for advanced biliary tract cancer; the Phase III KEYNOTE-966 study[8]The results showed that pembrolizumab combined with the GC regimen achieved a positive OS outcome in improving survival benefits for patients with advanced biliary tract cancer, further reinforcing the survival benefits that immunotherapy combined with chemotherapy can bring to these patients. The excellent outcomes demonstrated by these two studies mark the official entry of treatment for advanced biliary tract cancer into a new era of immunotherapy combined with chemotherapy.

In the field of biliary tract cancer, the development of targeted drugs is also in full swing. For example, patients with cholangiocarcinoma who have FGFR2 fusion or rearrangement can choose Pemigatinib; Ivosidenib can bring survival benefits to patients with IDH1-mutated cholangiocarcinoma; DS-8201 can bring survival benefits to patients with HER2-positive biliary tract cancer.

Durvalumab Approved for Biliary Tract Cancer in China, Benefiting More Chinese Patients

The TOPAZ-1 study has brought advanced biliary tract cancer into the era of immunotherapy. On November 7, 2023, durvalumab was approved for marketing in China for patients with locally advanced or metastatic biliary tract cancer, bringing new hope to the treatment of biliary tract cancer. It is also expected that durvalumab will benefit more Chinese patients.

References

[1]. Hai-Min Weng, Jie-Er Ying. Research progress in precision targeted therapy for biliary tract malignancies [J]. Chinese Journal of Hepatobiliary Surgery, 2022, 28(12): 955-960.

[2].Banales JM, Cardinale V, Carpino G, et al. Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA). Nat Rev Gastroenterol Hepatol. 2016 May;13(5):261-80.

[3].Turkes F, Carmichael J, Cunningham D, et al. Contemporary Tailored Oncology Treatment of Biliary Tract Cancers. Gastroenterol Res Pract. 2019 Dec 18;2019:7698786.

[4].Oh DY, He AR,Qin SK, et al.Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer.NEJM Evid 2022;1(8).

[5].Oh DY, He AR,Qin SK, et al. Updated overall survival from the Phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in patients with advanced biliary tract cancer.2022 ESMO. Poster 78P.

[6].Oh DY, He AR,Qin SK, et al.A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin (GemCis) in patients (pts) with advanced biliary tract cancer (BTC): TOPAZ-1.2022 ASCO-GI. Abstract 378.

[7]. "CSCO Guidelines for the Diagnosis and Treatment of Biliary Tract Malignancies (2022)".

[8].Kelley RK, Ueno M, Yoo PC, et al. Pembrolizumab 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,Apr 16.

Editorial Responsibility: Oncology News-QTT
Typesetting Editor: Oncology News-Chloe

Copyright belongs to Oncology News. Individuals are welcome to forward and share, but any other media or website that wishes to reprint or quote the content owned by this website must obtain authorization and clearly indicate at a prominent location “Reprinted from: Good Doctor Hui - Oncology Doctor APP”.