EMA Reviews Opdivo as Adjuvant Therapy for Resected Esophageal and Gastroesophageal Junction Cancer Following Chemoradiotherapy

January 14, 2021 News /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the European Medicines Agency (EMA) has accepted a Marketing Authorization Application (MAA) for the anti-PD-1 therapy Opdivo (Opdivo, generic name: nivolumab), as an adjuvant treatment for adult patients with esophageal or gastroesophageal junction (GEJ) cancer who have residual pathological disease after neoadjuvant chemoradiotherapy (CRT) and resection. The EMA will initiate a centralized review procedure to evaluate the MAA.

This application is based on the results of the Phase 3 CheckMate-577 trial. The data show that in patients with esophageal cancer and gastroesophageal junction (GEJ) cancer who received neoadjuvant chemoradiotherapy (CRT) and surgical resection,Compared with placebo, adjuvant Opdivo therapy doubled the disease-free survival (DFS) duration in patients (median DFS: 22.4 months vs. 11.0 months).. Currently, the standard of care for patients with esophageal and gastroesophageal junction (GEJ) cancer who have undergone neoadjuvant concurrent chemoradiotherapy and surgical resection is surveillance follow-up. The study resultsFirst confirmation that adjuvant therapy significantly prolongs disease-free survival in this patient population。

Bristol-Myers Squibb GastrointestinalTumorIan M. Waxman, MD, Head of Development, stated, “Most patients with locally advanced esophageal cancer do not achieve a complete response after receiving concurrent chemoradiotherapy and surgery. The unacceptably high risk of recurrence underscores the critical need for more effective treatment regimens. The EMA’s acceptance of the Opdivo MAA represents a significant advance for the esophageal cancer community, and we look forward to making Opdivo available to eligible patients in the EU who may benefit from it.”

Esophageal Cancer (Image source: medindia.net)

CheckMate-577 is a randomized, double-blind, multicenter Phase 3 study designed to evaluate the efficacy and safety of Opdivo as adjuvant therapy in patients with resectable esophageal cancer and gastroesophageal junction (GEJ) cancer who did not achieve pathological complete response after neoadjuvant chemoradiotherapy. The primary endpoint was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). After receiving neoadjuvant concurrent chemoradiotherapy andTumorFollowing complete resection (also known as “trimodality therapy”), 794 patients were randomized to either the placebo group (N=262) or the Opdivo group (N=532). Patients in the Opdivo group received Opdivo 240 mg via intravenous infusion every 2 weeks for 16 weeks, followed by sequential administration of Opdivo 480 mg via intravenous infusion every 4 weeks until disease recurrence, unacceptable toxicity, or withdrawal of informed consent by the patient, with a maximum total treatment duration of one year.

The study results were announced in September 2020, showing that compared to the placebo group, the Opdivo group demonstrated statistically significant and clinically meaningful improvements in the primary endpoint of disease-free survival (DFS). Compared to the placebo group (11.0 months; 95% CI: 8.3-14.3), the median DFS for patients treated with Opdivo post-surgery was doubled (22.4 months vs. 11.0 months; HR=0.69; p=0.0003). The median treatment duration for patients in the Opdivo group exceeded 10 months (10.1 months).

In the study, the safety profile of Opdivo monotherapy was consistent with that reported in previous studies. Compared with placebo, Opdivo demonstrated a favorable safety and tolerability profile. In the Opdivo group, the majority of patients (89%) were able to receive ≥90% of the relative dose intensity. Among patients receiving Opdivo, the incidence rates of all-grade and Grade 3–4 treatment-related adverse events (TRAEs) were 71% and 13%, respectively, compared with 46% and 6%, respectively, in the placebo group. In the Opdivo group, fewer than 10% of patients experienced serious TRAEs (all grades: 8%; Grades 3–4: 5%), compared with 3% and 1%, respectively, in the placebo group. The discontinuation rates due to TRAEs of any grade were low in both groups (Opdivo group: 9%; placebo group: 3%).

Esophageal cancer is the seventh most common cancer and the sixth leading cause of cancer-related deaths worldwide. In 2018, there were approximately 572,000 new cases of esophageal cancer globally, with over 508,000 deaths. In China, esophageal cancer is the sixth most common cancer and the fourth leading cause of cancer-related deaths, following lung cancer, gastric cancer, andLiver CancerSubsequently, squamous cell carcinoma and adenocarcinoma remain the two most common types of esophageal cancer, accounting for nearly 85% and 15% of all esophageal cancer cases, respectively. Most patients are diagnosed at an advanced stage, with their daily lives, including dietary habits, being significantly affected.

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. In 2018, there were over 1 million new cases of gastric cancer globally, with approximately 783,000 deaths. The definition of gastric cancer is relatively broad, encompassing various cancers that arise in the stomach and the gastroesophageal junction (GEJ), including GEJ cancers. Although the prevalence of GEJ cancer is lower than that of gastric cancer, it has been showing a continuous upward 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, 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 (Opdivo) was approved for marketing in China in June 2018, becoming the first approved immunotherapy in the Chinese market.Tumor(I-O) therapeutic agent. 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). (Bioon.com)

Original Source: European Medicines Agency Validates Bristol Myers Squibb’sapplication for Opdivo (nivolumab) as Adjuvant Treatment for Resected Esophageal or Gastroesophageal Junction Cancer Following Chemoradiotherapy