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Home CHMP Recommends Approval of Opdivo (Nivolumab) as Adjuvant Therapy for Esophageal and Gastroesophageal Junction Cancer, Significantly Extending Disease-Free Survival

CHMP Recommends Approval of Opdivo (Nivolumab) as Adjuvant Therapy for Esophageal and Gastroesophageal Junction Cancer, Significantly Extending Disease-Free Survival

Jun 28, 2021 00:25 CST Updated 00:25
Bristol-Myers Squibb

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.


Esophageal cancer (Image source: medindia.net)

June 27, 2021 News /BioonBIOON/ -- 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 the approval of the anti-PD-1 therapy Opdivo (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 surgical resection.

The CHMP opinion will now be submitted to the European Commission (EC) for review, which typically issues an approval decision within the next two months. If approved,Opdivo will become the first and only adjuvant treatment option in the EU to significantly improve disease-free survival (DFS) in the aforementioned patients.。

In May 2021, Opdivo received U.S.FDAApproved for the adjuvant treatment of adult patients with esophageal or GEJ cancer who have residual pathologic disease after neoadjuvant chemoradiotherapy (CRT) and resection. In the U.S., Opdivo is the first and only immunotherapy approved for this patient population.

Both locally advanced esophageal cancer and GEJ cancer are aggressive.TumorFor this type, a multimodal treatment approach is typically required, including chemotherapy, radiotherapy, and surgery. Patients with esophageal and gastroesophageal junction (GEJ) cancers who have residual pathologic disease following neoadjuvant chemoradiotherapy (CRT) and complete resection face a high risk of disease recurrence; however, the primary management strategy remains surveillance.

CHMP Positive Opinion andFDAapproval, were both based on the results of the Phase 3 CheckMate-577 trial. Data showed that, among patients with esophageal or gastroesophageal junction (GEJ) cancer who had residual pathologic disease following neoadjuvant chemoradiotherapy (CRT) and surgical resection,Compared with placebo, adjuvant Opdivo doubled patients' disease-free survival (DFS) (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. These results demonstrate for the first time that adjuvant therapy significantly prolongs disease-free survival in this patient population.

Ian M. Waxman, Head of Gastrointestinal Cancer Development at Bristol-Myers Squibb, said: “For many patients with locally advanced esophageal or gastroesophageal junction cancer, the risk of recurrence remains high even after neoadjuvant chemoradiotherapy and surgery, underscoring the need for additional treatment options. We believe that the early use of immunotherapy is critically important, as it has the potential to prevent recurrence. The CHMP’s positive recommendation for Opdivo as adjuvant therapy for esophageal or gastroesophageal junction cancer represents a treatment advancement for patients with these cancers.”

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 and gastroesophageal junction (GEJ) cancer who do not achieve a pathological complete response following neoadjuvant chemoradiotherapy (CRT). The primary endpoint of the study is disease-free survival (DFS), and the secondary endpoint is overall survival (OS). Following neoadjuvant concurrent chemoradiotherapy andTumorFollowing complete 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 withdrawal of informed consent, with a maximum total treatment duration of one year.

The results showed: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 Opdivo group demonstrated a 31% reduction in the risk of disease recurrence or death (HR = 0.69; 95% CI: 0.56–0.85; p = 0.0003).

Exploratory analysis showed: In patients with adenocarcinoma (n=563, 70.9%), mPFS was 19.4 months (95% CI: 15.9-29.4) in the Opdivo group, and mDFS was 11.1 months (95% CI: 8.3-16.8) in the placebo group (unstratified HR=0.75; 95% CI: 0.59-0.96). In patients with squamous cell carcinoma (n=230, 29%), mDFS was 29.7 months (95% CI: 14.4-NE) in the Opdivo group, and mDFS was 11.0 months (95% CI: 7.6-17.8) in the placebo group (unstratified HR=0.61; 95% CI: 0.42-0.88).

In this study, the safety of Opdivo monotherapy was consistent with that reported in previous studies.

Esophageal cancer is the seventh most common cancer globally and the sixth leading cause of cancer death. In 2020, there were approximately 600,000 new cases of esophageal cancer worldwide, with over 540,000 deaths. In China, esophageal cancer is the sixth most common cancer and the fourth leading cause of cancer mortality, 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 patients, respectively. Most esophageal cancer patients are diagnosed at an advanced stage, and their daily lives, including dietary intake, are significantly affected.

Gastric cancer is the fifth most common cancer worldwide and the third leading cause of cancer-related deaths. In 2020, there were over 1 million new cases of gastric cancer globally, resulting in approximately 770,000 deaths. The definition of gastric cancer is relatively broad, encompassing various malignancies classified under this category, including gastroesophageal junction (GEJ) cancer, which arises at the interface of the stomach and esophagus. Although the incidence of GEJ cancer is lower than that of gastric cancer overall, it exhibits 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 to induce cancer cell death, and is indicated for the treatment of multiple types ofTumorpotential. To date, Opdivo has been approved for multiple cancer indications.

Opdivo (Oudiwo) was approved for launch in China in June 2018, becoming the first approved immunotherapy in the Chinese market.Tumor(I-O) therapeutic drug. 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 have previously received two or more systemic therapy regimens. The approval of this gastric/gastroesophageal junction adenocarcinoma indication marks the third indication for Opdivo approved in China, following non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). (Bioon.com)