BMS Secures EU Approval and China NMPA Clearance in August for Opdivo (Nivolumab) Plus Chemotherapy as First-Line Treatment for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma

October 22, 2021 /BioonBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the European Commission (EC) has approved the anti-PD-1 therapy Opdivo (generic name: nivolumab), in combination with fluoropyrimidine- and platinum-based combination chemotherapy, for first-line treatment ofTumorAdult patients with PD-L1-expressing (CPS ≥5), HER2-negative, advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC). In the aforementioned patient population,Opdivo plus chemotherapy is the first treatment regimen to demonstrate superior overall survival (OS) and progression-free survival (PFS) compared to chemotherapy alone.

This approval is based on the results of the pivotal Phase 3 CheckMate-649 study, with data showing: (1)In patients with unresectable advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC) with PD-L1 expression (CPS ≥ 5) and HER2-negative status, first-line treatment with Opdivo plus chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone.。（2）inTumorIn both the PD-L1-expressing population with a CPS ≥ 1 and the overall randomized population, first-line treatment with Opdivo plus chemotherapy also significantly improved overall survival (OS) compared with chemotherapy.

Regarding US regulatory affairs, this April, the USFDAApproved Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adult patients with advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, and esophageal adenocarcinoma (EAC), regardless of PD-L1 expression status. In the United States, Opdivo is the first immunotherapy to significantly improve overall survival (OS) compared to chemotherapy alone when used in combination with chemotherapy. Opdivo plus chemotherapy will become the new standard of care for these patients.

Dr. Ian M. Waxman, M.D., Head of Gastrointestinal Cancer Research and Development at Bristol-Myers Squibb, stated: “This approval marks a significant advancement in the treatment of gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma, providing patients with a new treatment option that significantly improves overall survival (OS) compared to standard-of-care chemotherapy. Over the past decade, progress in the treatment of HER2-negative gastric cancer has been limited, and we are highly encouraged to continue advancing this field and to bring this Opdivo-based combination therapy to patients in Europe.”

Esophageal cancer (Image source: medindia.net)

CheckMate-649 is a randomized, multicenter, open-label study conducted in patients with previously untreated, non-HER2-positive, unresectable advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma, evaluating the efficacy and safety of Opdivo in combination with chemotherapy (5-fluorouracil + folinic acid + oxaliplatin regimen [mFOLFOX6]; or capecitabine + oxaliplatin regimen [CapeOX]) versus chemotherapy (mFOLFOX6 or CapeOX) as first-line treatment.

The results of this study were released in September 2020, showing that,Compared with the chemotherapy group, the Opdivo plus chemotherapy group demonstrated statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS).

Notably, in the treatment of patients with gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma, Opdivo is the first PD-1 inhibitor to demonstrate OS and PFS benefits when used in combination with chemotherapy compared with chemotherapy alone. In`Tumor`OS and PFS benefits were observed in patients with PD-L1-positive expression (Combined Positive Score [CPS] ≥5), meeting the two primary endpoints of the study. Additionally, an OS benefit was also observed in the overall randomized population.

The specific data were as follows: In PD-L1-positive patients with a CPS ≥5, the median OS was 14.4 months (95% CI: 13.1-16.2) in the Opdivo + chemotherapy group, compared with 11.1 months (95% CI: 10.0-12.1) in the chemotherapy group, representing a statistically significant difference (HR=0.71; 98.4% CI: 0.59-0.86; p<0.0001). The median PFS was 7.7 months (95% CI: 7.0-9.2) in the Opdivo + chemotherapy group versus 6.0 months (95% CI: 5.6-6.9) in the chemotherapy group, which was also statistically significant (HR: 0.68; 98% CI: 0.56-0.81; p<0.0001). In this trial, the safety profile of Opdivo plus chemotherapy was consistent with the known safety profiles of Opdivo and chemotherapy, with no new safety signals observed.

A statistically significant OS benefit was also observed with Opdivo in combination with chemotherapy in both the PD-L1-positive patient population with CPS ≥ 1 and the overall randomized patient population. In the overall randomized patient population, the median OS was 13.8 months (95% CI: 12.6–14.6) for patients receiving Opdivo plus chemotherapy compared with 11.6 months (95% CI: 10.9–12.5) for those receiving chemotherapy alone, demonstrating a statistically significant difference (HR: 0.80; 99.3% CI: 0.68–0.94; p = 0.0002). In PD-L1-positive patients with CPS ≥ 1, the median OS was 14.0 months (95% CI: 12.6–15.0) for patients receiving Opdivo plus chemotherapy compared with 11.3 months (95% CI: 10.6–12.3) for those receiving chemotherapy alone, also demonstrating a statistically significant difference (HR: 0.77; 99.3% CI: 0.64–0.92; p = 0.0001).

The incidence of serious treatment-related adverse events (TRAEs), for all grades and grades 3–4, was slightly higher in patients treated with Opdivo plus chemotherapy (all grades: 22%; grades 3–4: 17%) than in patients receiving chemotherapy alone (all grades: 12%; grades 3–4: 10%). Among patients receiving Opdivo plus chemotherapy, 36% and 17% experienced discontinuation due to TRAEs of any grade or grades 3–4, respectively, compared with 24% and 9% in those receiving chemotherapy alone. In patients treated with Opdivo plus chemotherapy, the incidence of TRAEs was consistent across patient subgroups.

Esophageal cancer is the eighth most common cancer globally and the sixth leading cause of cancer-related death. In 2020, there were approximately 600,000 new cases of esophageal cancer worldwide, with over 540,000 deaths. Squamous cell carcinoma and adenocarcinoma are the two most common types of esophageal cancer, accounting for nearly 85% and 15% of all cases, respectively. Most patients are diagnosed at an advanced stage, and their daily life, including dietary intake, is adversely affected. Although the histological distribution of esophageal cancer varies by region, the incidence of esophageal adenocarcinoma is highest in North America (65%) and Europe (approximately 40%).

Gastric cancer is the fifth most common cancer globally and the fourth leading cause of cancer-related death. In 2020, there were over 1 million new cases and approximately 770,000 deaths worldwide. The definition of gastric cancer is relatively broad, encompassing various malignancies, including gastroesophageal junction (GEJ) cancer originating at the junction of the stomach and esophagus. Compared with gastric cancer, although the incidence of GEJ cancer is lower, it demonstrates a steadily increasing trend.

Opdivo is a PD-(L)1 cancer immunotherapy designed to harness the body's own immune system to fight cancer. By blocking the PD-1/PD-L1 signaling pathway, it induces cancer cell death and is indicated for the treatment of multiple types ofTumorpotential. To date, Opdivo has been approved for multiple cancer indications.

In China, Opdivo (Oudiwo) received marketing approval in June 2018, becoming the first approved immuneTumor(I-O) therapeutic drugsTo date, Opdivo has been approved for multiple indications:

—— June 2018, indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that is epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK)-negative, and who have experienced disease progression following or intolerance to prior platinum-based chemotherapy.

—— August 2019, indicated for the treatment of patients whose disease has progressed during or following platinum-containing therapy and who have PD-L1-positive tumors (expressing PD-L1Tumorpatients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) (cells ≥1%).

—— In March 2020, indicated for the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who have previously received two or more systemic therapy regimens.

——In June 2021, Opdivo in combination with Yervoy (ipilimumab injection) was approved for the treatment of adult patients with unresectable, treatment-naïve, non-epithelioid malignant pleural mesothelioma. This marks the first indication approved in China for a dual immunotherapy combination, signifying the official launch in China of Yervoy, the world's first CTLA-4 inhibitor.

—— In August 2021, Opdivo in combination with fluoropyrimidine- and platinum-containing chemotherapy was approved for the first-line treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma. This is China's first immuno-# Tumor(I-O) drug approved for the first-line treatment indication of advanced gastric cancer; Opdivo is also currently the only PD-1 inhibitor with a gastric cancer indication in China. (Bioon.com)

Original Source:Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) + Chemotherapy for Patients with HER2 Negative, Advanced or Metastatic Gastric, Gastroesophageal Junction or Esophageal Adenocarcinoma whose Tumors Express PD-L1 with CPS ≥5