Bristol Myers Squibb Announces China Approval of Two Esophageal Cancer Indications for Opdivo® (Nivolumab), Marking the Most Comprehensive Coverage in Upper GI Immuno-Oncology

Achieving the broadest range of approved indications for upper gastrointestinal tumor immunotherapy in China to date"The Most Comprehensive Coverage"^[1]

ShanghaiJune 27, 2022/PR Newswire/ -- Bristol-Myers Squibb announced that the PD-1 inhibitorOpdivo^®(Nivolumab Injection) Approved by China's National Medical Products Administration for Two New Esophageal Cancer Indications:

This approval marksOpdivoAndOpdivoCombined chemotherapy has become the first and currently only PD-1/PD-L1 inhibitor in China to cover both adjuvant treatment for esophageal cancer and first-line treatment for advanced stages; as well as the first and currently only PD-1/PD-L1 inhibitor covering first-line treatment for upper gastrointestinal tumors.^[2](Regardless of histological subtype (squamous cell carcinoma, adenocarcinoma) and tumor location (stomach, esophagus, gastroesophageal junction)).

Frontline Breakthrough Fills the Gap, Leading the Era of Immune Adjuvant "Food"

OpdivoThe approval of adjuvant therapy indications for esophageal cancer is based on the CheckMate -577 study. CheckMate -577 is a global, large-scale, Phase III, randomized, multicenter, double-blind clinical study that evaluatedOpdivoEfficacy of postoperative adjuvant treatment for patients with esophageal cancer or gastroesophageal junction cancer who have undergone complete resection after preoperative neoadjuvant concurrent chemoradiotherapy and have pathological residual disease. This is the world's first and currently the only Phase III study on immune adjuvant therapy for esophageal cancer to achieve positive results.

According to the latest 14-month follow-up data, the primary endpoint results of the study showed,OpdivoCompared with the control group, it can double the median disease-free survival (DFS) of postoperative patients to 22.4 months (10.4 months in the control group); patients can benefit regardless of PD-L1 expression status or histological subtype. A greater trend of DFS benefit was observed in Chinese patients with esophageal squamous cell carcinoma, which is highly prevalent in China:OpdivoThe median DFS of the esophageal squamous cell carcinoma group was 29.7 months, compared to 10.6 months in the control group.^[3]。

The results of the exploratory endpoint study showed,OpdivoCan nearly double the median distant metastasis-free survival (DMFS) period in patients to 29.4 months (16.6 months in the control group).^[3]. In the study,OpdivoNo unexpected safety signals were observed, and acceptanceOpdivoThe quality of life of treated patients remained unchanged compared to baseline.^[4]。 

"China is the world's largest country for esophageal cancer, with global proportions of new and death cases as high as 53.7% and 55.3%, respectively."^[5]For patients with locally advanced operable conditions, concurrent chemoradiotherapy is one of the current standard preoperative neoadjuvant treatments, but there is still about 70%.^[6] Patients who cannot achieve pathological complete remission face a higher risk of recurrence, especially those with distant metastases, for whom subsequent treatment is extremely challenging; moreover, this field has long lacked a proven effective standard adjuvant therapy.Professor Li Yin, Director of the Esophageal Disease Ward in the Thoracic Surgery Department at the Cancer Hospital of the Chinese Academy of Medical Sciences, stated"CheckMate -577 is the first major breakthrough in immunotherapy for adjuvant treatment of esophageal cancer, confirmingOpdivoIt can extend the median DFS of patients to double, with a median DMFS of nearly 30 months, without affecting the quality of life, which is of great significance for improving postoperative survival. This approval fills a clinical gap and is expected to redefine the perioperative treatment guidelines for esophageal cancer; it also strengthens our confidence in advancing immunotherapy to earlier stages of gastrointestinal tumors.

Based on the results of CheckMate -577,OpdivoHas been included in the Chinese Society of Clinical Oncology (CSCO)^[7]、National Comprehensive Cancer Network (NCCN)^[8]and other authoritative clinical diagnosis and treatment guidelines for esophageal cancer, becoming the only currently recommended immunotherapy drug for adjuvant treatment of esophageal cancer.

A New Choice for First-Line Treatment, Significant Benefits Demonstrate "Esophageal" Strength

OpdivoThe approval of the indication for combined chemotherapy as a first-line treatment for advanced esophageal squamous cell carcinoma is based on the CheckMate -648 study. CheckMate -648 is the largest Phase III immunotherapy study to date that has enrolled patients with esophageal squamous cell carcinoma, aiming to evaluate, compared with chemotherapy alone,OpdivoCombination chemotherapy, orOpdivoCombined CTLA-4 InhibitorYiwo^®(Efficacy and Safety of Ipilimumab in the First-Line Treatment of Patients with Advanced Esophageal Squamous Cell Carcinoma)

The study results showed that, in all randomized populations,OpdivoCombined chemotherapy significantly improves overall survival (OS) compared to single-agent chemotherapy.OpdivoThe median OS was 13.2 months in the combination chemotherapy group and 10.7 months in the single-agent chemotherapy group.OpdivoThe combination chemotherapy group also showed a clinically meaningful improvement in objective response rate (ORR),OpdivoThe ORR was 47% in the combination chemotherapy group and 27% in the single-agent chemotherapy group.^[9]。

In patients with tumor expression of PD-L1 ≥ 1%,OpdivoA greater benefit was observed with combination chemotherapy, with a median OS of 15.4 months, extending OS by more than 6 months compared to chemotherapy alone (9.1 months in the chemotherapy group), reducing the risk of death by 46%.OpdivoThe ORR (53%) of the combination chemotherapy group was 2.5 times that of simple chemotherapy (20%).^[9]。

In the study,OpdivoNo unexpected safety signals were observed with combination chemotherapy.

"In Chinese patients with esophageal cancer, those with squamous cell carcinoma account for more than 90%."^[10]CheckMate –648 is the largest Phase III clinical study of immunotherapy to date that has included patients with esophageal squamous cell carcinoma, and it involved a significant number of Chinese patients. Therefore, its results are highly relevant for first-line diagnosis and treatment of advanced esophageal squamous cell carcinoma in China.Professor Xu Jianming, Director of the Cancer Center at the First Medical Center of the PLA General Hospital, stated,"OpdivoThe regimen can significantly improve OS in first-line treatment patients; moreover, PD-L1 positive patients tend to benefit more, with an increase in median OS of more than half a year. This approval further expands the treatment options for first-line esophageal squamous cell carcinoma, bringing hope of improved efficacy to more Chinese patients. Not only that, but the study also...OpdivoCombined CTLA-4 InhibitorYiwoIt also demonstrated significant efficacy, substantially improving the median OS in the overall population compared to chemotherapy alone. This is the first 'chemotherapy-free' regimen in this field, and we are highly anticipating its availability to benefit patients in China as soon as possible."

Comprehensive Coverage of the Upper Digestive Tract: Embarking on a "Stomach" and "Food" Era Journey

After this approval,OpdivoAndOpdivoCombination chemotherapy has been approved in China for four indications of upper gastrointestinal tumors (including esophageal cancer, gastroesophageal junction cancer, and gastric cancer).^[11], ranking first among all PD-1/PD-L1 inhibitors.

"OpdivoThe simultaneous approval of two esophageal cancer indications this time highlights Bristol-Myers Squibb's determination and efforts to implement the 'China 2030 Strategy' and accelerate the introduction of global innovative products and indications.Ms. Chen Siyuan, President of Bristol-Myers Squibb China"On the 40th anniversary of Bristol-Myers Squibb's entry into mainland China,Opdivo"And its combination therapy regimen has achieved the 'widest coverage' of indications for immunotherapy in the field of upper gastrointestinal tumors to date. This demonstrates our long-term dedication to addressing high-incidence diseases in China, striving to meet the unmet needs of Chinese patients, and leading innovative treatments for upper gastrointestinal tumors through relentless efforts. Moving forward, we will actively leverage our strengths in exploring earlier-stage cancers to further expand the application of immunotherapy; at the same time, we will collaborate with all parties to enhance the accessibility of innovative drugs and transform patient lives."

Since 2018OpdivoSince becoming the first approved immuno-oncology treatment in China, Bristol-Myers Squibb has remained highly committed to the accessibility of innovative treatments for Chinese patients, and in 2019, supported the launch of an initiative by the China Cancer Foundation (CFC).OpdivoPatient Assistance Program. Following this approval, the China Cancer Foundation announced,OpdivoThe "Patient Assistance Program" will expand to include adjuvant treatment for esophageal cancer or gastroesophageal junction cancer and first-line advanced esophageal squamous cell carcinoma, benefiting more Chinese cancer patients and helping them gain access to improved treatment outcomes.

Opdivo Combined with Yervoy for First-Line Treatment of Advanced Esophageal Squamous Cell Carcinoma Not Yet Approved in China

The information contained in this material is for reference only. Please follow the advice or guidance of doctors or other healthcare professionals..

[1] According to the statistics of public information as of April 21, 2021.

[2] Based on the CheckMate-649 study, Opdivo received NMPA approval in 2021 for first-line treatment in combination with chemotherapy for patients with advanced or metastatic gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma.

[3] Moehler, M et al 2021, Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer following neoadjuvant chemoradiotherapy: 14-month follow-up of CheckMate 577, Poster 1381P, presented at the ESMO Virtual Congress 2021, September 16-21.

[4] Kelly, RJ et al 2021, Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med 2021; 384:1191-1203. DOI: 10.1056/NEJMoa2032125.

[5] Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.fr/today.

[6] Blum MM et al. 2017, Pathological complete response in patients with esophageal cancer after the trimodality approach: the association with baseline variables and survival — the University of Texas MD Anderson Cancer Center experience. Cancer 2017;123:4106-4113.

[7] Guidelines Working Committee of the Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) Esophageal Cancer Diagnosis and Treatment Guidelines 2021. People's Health Publishing House, 2021.4.

[8] National Comprehensive Cancer Network. (2022). Esophageal and Esophagogastric Junction Cancers (version 2.2022). Retrieved from https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf.

[9] Doki, Y et al. 2022, Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma. N Engl J Med 2022; 386:449-62.

[10] National Health Commission of the People's Republic of China. Guidelines for Diagnosis and Treatment of Esophageal Cancer (2018 Edition) [J/CD]. Chinese Journal of Digestive Diseases and Imaging (Electronic Edition), 2019, 9(4): 158-192.

[11] For specific approved indications, please refer to the "About Opdivo" section at the end.