Bristol Myers Squibb Receives European Commission Approval for Opdivo (Nivolumab) as Adjuvant Therapy in Esophageal and Gastroesophageal Junction Cancer Patients with Residual Pathologic Disease Post Chemoradiotherapy

Bristol-Myers Squibb (BMS) recently announced that the European Commission (EC) has approved the anti-PD-1 therapy Opdivo (Chinese brand name: Oudiwo; generic name: nivolumab) for the adjuvant treatment of adult patients with esophageal or gastroesophageal junction (GEJ) cancer who have residual pathological disease following neoadjuvant chemoradiotherapy (CRT) and resection.

Locally advanced esophageal cancer and GEJ cancer are both aggressive malignancies that typically require multimodal therapy, including chemotherapy, radiotherapy, and surgery. Patients with esophageal or GEJ cancer who have pathologic residual disease following neoadjuvant CRT and complete resection face a high risk of disease recurrence; however, surveillance remains the primary option, underscoring an urgent need for additional treatment strategies.

Opdivo is the first adjuvant treatment option in the European Union to significantly improve disease-free survival (DFS) in these patients. In May 2021, Opdivo received U.S. FDA approval for the adjuvant treatment of adult patients with esophageal or gastroesophageal junction (GEJ) cancer who have residual pathologic disease following neoadjuvant chemoradiotherapy (CRT) and surgical resection. In the United States, Opdivo is the first immunotherapy approved for this patient population.

The European Commission’s approval decision is based on the results of the Phase III CheckMate-577 trial. Data show that in patients with esophageal or gastroesophageal junction (GEJ) cancer who have residual pathologic disease after neoadjuvant chemoradiotherapy (CRT) and complete surgical resection, adjuvant therapy with Opdivo doubled disease-free survival (DFS) compared with placebo (median DFS: 22.4 months vs. 11.0 months). Currently, the standard of care for patients with esophageal or GEJ cancer following neoadjuvant concurrent chemoradiotherapy and surgical resection is observation. These results demonstrate for the first time that adjuvant therapy can significantly prolong DFS in this patient population.

Ian M. Waxman, Head of Gastrointestinal Cancer Development at Bristol-Myers Squibb, stated: “We have demonstrated that the use of immunotherapy in early-stage cancer has the potential to prevent recurrence in certain patients. BMS was the first company to introduce a checkpoint inhibitor as adjuvant therapy for patients with melanoma. Now, we are pleased to be the first to bring adjuvant therapy to patients with esophageal or gastroesophageal junction (GEJ) cancer in the EU, who continue to face a high unmet need. The EU approval of Opdivo as adjuvant therapy for esophageal or GEJ cancer represents a treatment advancement for these patients and will help reduce the risk of recurrence.”

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 or gastroesophageal junction (GEJ) cancer who have not achieved a pathologic complete response following neoadjuvant chemoradiotherapy (CRT). The primary endpoint is disease-free survival (DFS), and the secondary endpoint is overall survival (OS). Following neoadjuvant concurrent chemoradiotherapy and complete tumor resection (also known as "trimodality therapy"), 794 patients were randomized to 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 Opdivo 480 mg via intravenous infusion every 4 weeks, until disease recurrence, unacceptable toxicity, or patient withdrawal of informed consent, with a maximum total treatment duration of one year.

Results showed that the median progression-free survival (mPFS) in the Opdivo treatment group was twice that of the placebo group (22.4 months vs. 11.0 months). Compared with the placebo group, the risk of disease recurrence or death was reduced by 31% in the Opdivo group (HR=0.69; 96.4% CI: 0.56-0.86; p=0.0003).

Exploratory analysis showed that: In patients with adenocarcinoma (n=563, 70.9%), the mPFS in the Opdivo arm was 19.4 months (95% CI: 15.9–29.4), and the mDFS in the placebo arm was 11.1 months (95% CI: 8.3–16.8) (unstratified HR=0.75; 95% CI: 0.59–0.96). In patients with squamous cell carcinoma (n=230, 29%), the mDFS in the Opdivo arm was 29.7 months (95% CI: 14.4–NE), and the mDFS in the placebo arm was 11.0 months (95% CI: 7.6–17.8) (unstratified HR=0.61; 95% CI: 0.42–0.88). During the study, the safety profile of Opdivo monotherapy was consistent with that reported in previous studies.

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 worldwide, with over 540,000 deaths. In China, esophageal cancer ranks as the sixth most common cancer and the fourth leading cause of cancer mortality, following lung, gastric, and liver cancers. Squamous cell carcinoma and adenocarcinoma remain the two most prevalent histological types, accounting for nearly 85% and 15% of all cases, respectively. The majority of patients are diagnosed at an advanced stage, which significantly impacts their daily lives, including dietary intake.

Gastric cancer is the fifth most common cancer globally and the third leading cause of cancer death. In 2020, there were over 1 million new cases of gastric cancer worldwide, with approximately 770,000 deaths. The definition of gastric cancer is relatively broad, encompassing various malignancies classified as gastric cancer, including gastroesophageal junction (GEJ) cancer, which develops at the junction of the stomach and esophagus. Compared with gastric cancer, GEJ cancer has a lower incidence but exhibits a continuously 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 has the potential to treat various types of tumors. To date, Opdivo has been approved for multiple cancer indications.

In China, Opdivo (Oudiwo) was granted marketing approval in June 2018, becoming the first approved immuno-oncology (I-O) therapy in the Chinese market. According to the prescribing information on the BMS website, Opdivo has been approved for three indications in China to date: （1）as a monotherapy for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are epidermal growth factor receptor (EGFR) mutation-negative and anaplastic lymphoma kinase (ALK)-negative, and whose disease has progressed or who are intolerant to prior platinum-based chemotherapy. （2）as a monotherapy for the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have experienced disease progression during or after platinum-based therapy and whose tumors are PD-L1 positive (defined as PD-L1 expression on ≥1% of tumor cells). （3）for the treatment of patients with advanced or recurrent gastric or gastroesophageal junction adenocarcinoma who have previously received two or more systemic therapy regimens.

Original Source: Bristol Myers Squibb Receives European Commission Approval for Opdivo (nivolumab) as Adjuvant Treatment for Esophageal or Gastroesophageal Junction Cancer Patients with Residual Pathologic Disease Following Chemoradiotherapy

Original Title:Postoperative Adjuvant Therapy for Esophageal/Gastroesophageal Junction Cancer! EU Approves Opdivo (nivolumab): Significantly Prolongs Disease-Free Survival!

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