EMA Validates Bristol Myers Squibb’s Application for Opdivo (Nivolumab) Plus Chemotherapy as First-Line Treatment for Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma

January 12, 2021 /Bio ValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the European Medicines Agency (EMA) has accepted a Class II variation application for the anti-PD-1 therapy Opdivo (generic name: nivolumab), in combination with fluoropyrimidine and platinum-based chemotherapy, for the first-line treatment of adult patients with advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC).

This application is based on the results of the pivotal Phase 3 clinical study (CheckMate-649). This was 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, to evaluate the efficacy and safety of Opdivo in combination with chemotherapy (folinic acid + 5-fluorouracil + oxaliplatin [FOLFOX] regimen; or capecitabine + oxaliplatin [CapeOX] regimen), Opdivo in combination with Yervoy (ipilimumab), and chemotherapy (FOLFOX or CapeOX) as first-line treatment.

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

Gastric Cancer (Image source: cancernetwork.com)

Statistically significant overall survival (OS) benefits were also observed with Opdivo plus chemotherapy in the PD-L1–positive population with a combined positive score (CPS) ≥1 and in the overall randomized population. In the overall randomized population, the median OS was 13.8 months (95% CI: 12.6–14.6) for patients receiving Opdivo plus chemotherapy versus 11.6 months (95% CI: 10.9–12.5) for those receiving chemotherapy alone, with a statistically significant difference (HR: 0.80; 99.3% CI: 0.68–0.94; p=0.0002). In the PD-L1–positive population with CPS ≥1, the median OS was 14.0 months (95% CI: 12.6–15.0) for patients receiving Opdivo plus chemotherapy versus 11.3 months (95% CI: 10.6–12.3) for those receiving chemotherapy alone, also showing 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 any grade and grades 3–4, was slightly higher in patients treated with Opdivo plus chemotherapy (any grade: 22%; grades 3–4: 17%) than in those receiving chemotherapy alone (any grade: 12%; grades 3–4: 10%). Among patients receiving Opdivo plus chemotherapy, 36% and 17% discontinued treatment due to TRAEs of any grade or grades 3–4, respectively, compared with 24% and 9%, respectively, among patients receiving chemotherapy alone. The incidence of TRAEs was consistent across different patient subgroups in the Opdivo plus chemotherapy group.

Ian M. Waxman, M.D., Head of Gastrointestinal Oncology Development at Bristol-Myers Squibb, stated: “Gastric cancer is one of the top three leading causes of cancer-related deaths worldwide, and a significant proportion of patients with metastatic gastric and esophageal cancers do not survive beyond one year after diagnosis.Today’s acceptance by the EMA marks a critical step toward advancing treatment options and improving patient outcomes.CheckMate-649 is the first global study in over a decade to demonstrate a significant benefit in overall survival (OS) compared with chemotherapy in patients receiving first-line treatment for non-HER2-positive gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma, highlighting the potential of Opdivo plus chemotherapy to become the new standard of care for these patients, regardless of theirTumorLocation.“We look forward to continuing our collaboration with the EMA to bring this important new first-line treatment option to patients.”

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, thereby inducing cancer cell death, and is indicated for the treatment of various typesTumorpotential. To date, Opdivo has been approved for multiple cancer indications.

Opdivo (Ouyiwo) was approved for launch in China in June 2018, becoming the first approved immuneTumor(I-O) therapeutic agents. In March 2020, the National Medical Products Administration (NMPA) approved Opdivo for the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who had previously received two or more systemic therapy regimens. This approval for gastric/gastroesophageal junction adenocarcinoma marks the third indication for Opdivo (Opdivo) in China, following non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN).

This approval is based on data from the multicenter, Phase 3 ATTRACTION-2 study. The study enrolled patients exclusively from East Asia (including Taiwan, China, Japan, and South Korea) and aimed to evaluate the efficacy and safety of Opdivo in the treatment of unresectable, previously treated advanced or recurrent gastric and gastroesophageal junction adenocarcinoma. The results demonstrated that, compared with the investigator’s choice of control regimen, Opdivo reduced the risk of death by 38% (median overall survival [OS]: 5.26 months vs. 4.14 months; HR=0.62 [95% CI: 0.51–0.76], p<0.0001), and doubled the one-year survival rate to 27.3% (12-month survival rate: 27.3% vs. 11.6%). (Bioon.com)

Original source: European Medicines Agency Validates Bristol Myers Squibb’sapplication for Opdivo (nivolumab) Combined with Chemotherapy as First-Line Treatment in Metastatic Gastric Cancer, Gastroesophageal Junction Cancer and Esophageal Adenocarcinoma