Esophageal Cancer (Image Source: medindia.net)
News on February 26, 2022 /
BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending approval of the anti-PD-1 therapy Opdivo (nivolumab) in combination with the anti-CTLA-4 therapy Yervoy (ipilimumab) as a first-line treatment.
TumorAdult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) expressing PD-L1≥1%.
Currently, two supplemental Biologics License Applications (sBLA) for Opdivo are under review by the U.S. FDA: Opdivo in combination with Yervoy, and Opdivo in combination with chemotherapy (containing fluorouracil + cisplatin), for first-line treatment of adult patients with unresectable advanced, recurrent, or metastatic ESCC. According to the Prescription Drug User Fee Act (PDUFA),
FDAThe target date for making the resolution is May 28, 2022.
Opdivo+Yervoy is the first immunotherapy combination to demonstrate significantly superior efficacy compared to chemotherapy in the aforementioned patient population. In the Phase 3 CheckMate-648 trial, the Opdivo+Yervoy regimen significantly extended overall survival (OS) compared to fluorouracil and platinum-based chemotherapy.
Ian M. Waxman, M.D., Head of Gastrointestinal Cancers Development at Bristol-Myers Squibb, said: "Currently, the median overall survival (OS) for patients with advanced ESCC on standard chemotherapy is approximately 10 months. The CHMP's positive opinion for Opdivo+Yervoy as a first-line treatment marks an important step forward in bringing a new treatment option to patients in Europe."
The positive review opinion of the CHMP is based on the results of the pivotal Phase 3 CheckMate-648 trial. The pre-specified interim analysis showed:
InTumorIn adult patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) expressing PD-L1≥1%, compared with chemotherapy (fluorouracil + platinum), the Opdivo+Yervoy regimen demonstrated statistically significant and clinically meaningful improvement in overall survival (OS) (median OS: 13.7 months vs 9.1 months; HR=0.64; 98.6% CI: 0.46-0.90; p=0.001).In the study, the safety of the Opdivo+Yervoy regimen was consistent with previously reported research.
Mechanism of Action of Opdivo and Yervoy
Esophageal cancer is the eighth most common cancer globally and the sixth leading cause of cancer-related deaths, with approximately 604,000 new cases and over 544,000 deaths in 2020. The two most common types of esophageal cancer are squamous cell carcinoma (ESCC) and adenocarcinoma, accounting for roughly 90% and 10% of all esophageal cancer cases, respectively, although histological variations may exist by region. The overall burden of ESCC is concentrated in Asia, where about 80% of global cases occurred in 2020. The majority of esophageal cancer cases are diagnosed at an advanced stage.
DiagnosisESCC most commonly occurs in the upper and middle parts of the esophagus, while adenocarcinoma starts in the cells of the mucus-secreting glands of the esophagus and most often occurs in the lower part of the esophagus.
Opdivo belongs to the PD-(L)1 tumor immunotherapy, designed to utilize the body's own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway to induce cancer cell death, showing potential in treating various types of tumors. To date, Opdivo has been approved for multiple cancer indications. In October 2015, Opdivo+Yervoy (Ouduo Yiwo) became the world’s first immunotherapy combination to receive regulatory approval.
TumorCombination therapy has now been approved in over 50 countries and regions worldwide for various types of tumors, including lung cancer and pleural mesothelioma.
Melanoma, Renal Cell Carcinoma, Colorectal Cancer,
Liver Cancer。
In esophageal cancer, Opdivo has been approved for three treatment indications, specifically: (1) for the treatment of patients with unresectable advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC) who have received fluoropyrimidine and platinum-based chemotherapy, regardless of PD-L1 expression level; (2) as adjuvant therapy for adult patients with esophageal or gastroesophageal junction (GEJ) cancer who have residual pathological disease after neoadjuvant chemoradiotherapy (CRT) and complete resection; (3) in combination with fluoropyrimidine and platinum-based chemotherapy, as first-line treatment for adult patients with advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC), regardless of PD-L1 expression status.
In China, Opdivo (Oudiwot) was approved for marketing in June 2018, becoming the first immunotherapy drug approved in the Chinese market.
TumorImmuno-Oncology (I-O) therapy drugs. To date, Opdivo has been approved by the National Medical Products Administration (NMPA) for multiple cancer types, including: non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), gastric cancer or gastroesophageal junction cancer or esophageal adenocarcinoma, malignant pleural mesothelioma, etc.
In China, Opdivo+Yervoy (O药+Y药) received NMPA approval in June 2021: for the treatment of adult patients with unresectable, previously untreated non-epithelioid malignant pleural mesothelioma. This is the first approved indication for the dual immunotherapy combination in China, marking the official launch of Yervoy, the world’s first CTLA-4 inhibitor, in China. (Bioon.com)
