BMS Receives Positive CHMP Opinion and China Approval for Opdivo Plus Chemotherapy as First-Line Treatment for Advanced Gastric, GEJ, and Esophageal Adenocarcinoma
Sep 19, 2021 10:26
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10:26
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.
Gastric Cancer
September 19, 2021 /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 ofAnti-PD-1 therapy Opdivo (Oudiwo, generic name: nivolumab), in combination with fluoropyrimidine- and platinum-based combination chemotherapy, for first-line treatmentTumorAdult patients with PD-L1–expressing, Combined Positive Score (CPS) ≥ 5, HER2-negative, advanced or metastatic gastric cancer (GC), gastroesophageal junction (GEJ) cancer, or esophageal adenocarcinoma (EAC).Now, the CHMP opinion will be submitted to the European Commission (EC) for review, which will typically issue a final decision within two months.
The CHMP's positive opinion is based on results from the pivotal Phase 3 CheckMate-649 study, with data showing:(1) In patients with unresectable advanced or metastatic GC, GEJ cancer, or EAC whose tumors express PD-L1 with a CPS ≥5 and are HER2-negative, first-line treatment with Opdivo plus chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy. (2) InTumorIn the patient population expressing PD-L1 with a CPS ≥ 1 and in the overall randomized population, first-line treatment with Opdivo + chemotherapy also significantly improved overall survival (OS) compared with chemotherapy.
Regarding US regulatory affairs, this April, the USFDAOpdivo has been approved 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, and esophageal adenocarcinoma (EAC), regardless of PD-L1 expression status. Notably, Opdivo is the first immunotherapy to significantly improve overall survival (OS) compared to chemotherapy alone when administered 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, said: “Gastric and gastroesophageal junction (GEJ) cancers, as well as esophageal adenocarcinoma, are among the most lethal cancers in the world, and for years, patients with HER2-negative disease have seen no major advances. Based on the results of the CheckMate -649 trial, Opdivo in combination with chemotherapy is the first regimen to demonstrate superior overall survival compared to chemotherapy alone in this patient population. We look forward to the European Commission’s decision to make this new therapy available to address the remaining high unmet medical need.”
Esophageal cancer (Image source: medindia.net)
CheckMate-649 is a randomized, multicenter, open-label study conducted in patients with previously untreated, HER2-negative, 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 plus leucovorin plus oxaliplatin [mFOLFOX6] or capecitabine plus oxaliplatin [CapeOX]) versus chemotherapy (mFOLFOX6 or CapeOX) as first-line treatment.
The results of this study were published in September 2020, demonstrating that compared with the chemotherapy group, the Opdivo plus chemotherapy group showed statistically significant and clinically meaningful improvements in overall survival (OS) and progression-free survival (PFS).
It is worth noting that,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 to chemotherapy alone. InTumorOS 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 are as follows: In PD-L1-positive patients with a CPS ≥ 5, the median OS for the Opdivo + chemotherapy group was 14.4 months (95% CI: 13.1–16.2), compared with 11.1 months (95% CI: 10.0–12.1) in the chemotherapy group, demonstrating a statistically significant difference (HR = 0.71; 98.4% CI: 0.59–0.86; p < 0.0001). The median PFS for the Opdivo + chemotherapy group was 7.7 months (95% CI: 7.0–9.2), versus 6.0 months (95% CI: 5.6–6.9) in the chemotherapy group, which also showed a statistically significant difference (HR: 0.68; 98% CI: 0.56–0.81; p < 0.0001). In this trial, the safety profile of the Opdivo + chemotherapy combination reflected the known safety profiles of Opdivo and chemotherapy, with no new safety signals observed.
A statistically significant OS benefit was also observed with Opdivo plus chemotherapy in the PD-L1-positive patient population with 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 and 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 those receiving Opdivo plus chemotherapy and 11.3 months (95% CI: 10.6-12.3) for those receiving chemotherapy alone, which was also statistically significant (HR: 0.77; 99.3% CI: 0.64-0.92; p=0.0001).
The incidence of treatment-related adverse events (TRAEs), of 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 patients receiving chemotherapy alone (any grade: 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%, respectively, in patients receiving chemotherapy alone. The incidence of TRAEs with Opdivo plus chemotherapy was consistent across different patient subgroups.
Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death worldwide. In 2020, there were approximately 600,000 new cases and over 540,000 deaths globally. Squamous cell carcinoma and adenocarcinoma are the two most common histological subtypes 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 significantly affected. Although the histological distribution of esophageal cancer varies by region, the highest incidence of esophageal adenocarcinoma is observed in North America (65%) and Europe (approximately 40%).
Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer-related death worldwide. In 2020, there were over 1 million new cases globally, with approximately 770,000 deaths. The definition of gastric cancer is relatively broad, encompassing various malignancies that can be classified under this category, including gastroesophageal junction (GEJ) cancer, which arises at the junction between the stomach and the esophagus. Although the incidence of GEJ cancer is lower than that of gastric cancer overall, it continues to show a steady upward trend.
Opdivo is a PD-(L)1 tumor immunotherapy designed to harness the body's own immune system to combat cancer by blocking the PD-1/PD-L1 signaling pathway to induce cancer cell death, with the potential to treat multiple types...Tumorthe potential. To date, Opdivo has been approved for multiple cancer indications.
In China, Opdivo was approved for marketing in June 2018, becoming the first approved immune in the Chinese market.Tumor(I-O) therapeutic drug. To date, Opdivo has been approved for multiple indications:
—— In June 2018, 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 after or who are intolerant to prior platinum-based chemotherapy.
——In August 2019, for the treatment of patients with disease progression during or after a platinum-containing regimen and whose tumors are PD-L1 positive (expressing PD-L1Tumor(cells ≥1%) patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
—— 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 (Yervoy, ipilimumab injection) was approved for the treatment of adult patients with unresectable, treatment-naïve, non-epithelioid malignant pleural mesothelioma. This marked the first indication approved in China for dual immunotherapy combination therapy, signifying the official launch of Yervoy, the world’s first CTLA-4 inhibitor, in China.
——In August 2021, Opdivo in combination with fluoropyrimidine- and platinum-based chemotherapy is indicated for the first-line treatment of patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. This is China's first immunoTumor(I-O) drug approved for the first-line treatment indication of advanced gastric cancer; Opdivo is also currently the only PD-1 inhibitor approved for gastric cancer indications in China. (Bioon.com)