Opdivo® (Nivolumab) Combined with Chemotherapy Approved as China's First and Only Neoadjuvant Immunotherapy for Non-Small Cell Lung Cancer

ShanghaiJanuary 17, 2023/PR Newswire/ -- Bristol-Myers Squibb announced that the PD-1 inhibitorOpdivo^®(Nivolumab Injection) has been approved by the China National Medical Products Administration (NMPA) for a new indication: in combination with platinum-based doublet chemotherapy (once every three weeks for three cycles), as neoadjuvant treatment for adult patients with resectable (tumor ≥4 cm or lymph node-positive) non-small cell lung cancer (NSCLC), regardless of PD-L1 expression level.OpdivoCombination chemotherapy is the first and currently the only approved immune-oncology therapy in China for neoadjuvant treatment of NSCLC.

This approval is based on a global large-scale clinical study codenamed CheckMate -816. The study evaluated three courses of treatment prior to surgery.OpdivoEfficacy and Safety of Neoadjuvant Chemotherapy Combined with Immunotherapy versus Chemotherapy Alone in Patients with Operable NSCLC. This is the world's first Phase III study to demonstrate that neoadjuvant immunotherapy combined with chemotherapy for NSCLC can bring significant clinical benefits.

CheckMate -816The main endpoint results of the study showed^[1]: Preoperative receiptOpdivoIn patients receiving neoadjuvant therapy with combination chemotherapy, 24% showed no viable tumor cells in both the primary tumor and lymph node specimens after surgical resection, achieving a pathological complete response (pCR), which is nearly 11 times the proportion observed in the chemotherapy group (2.2%).OpdivoCombination chemotherapy can significantly extend the median event-free survival (EFS) to 31.6 months, nearly 11 months longer than chemotherapy alone (20.8 months), and reduce the risk of disease progression, recurrence, or death by 37%.Risk of death.

Subgroup analysis showed^[1], patients regardless of pathological type (squamous or non-squamous), PD-L1 expression level (<1% or ≥1%), disease stage (IB-II or IIIA) can all benefit fromOpdivoBenefit from combined chemotherapy treatment. Moreover, the EFS benefit in the Asian population is numerically superior, reducing the risk of disease progression, recurrence, or death by 55%.。

Results of the exploratory analysis showed^[1]，OpdivoPatients in the combined chemotherapy group achieved a higher proportion of radiological downstaging compared to the single chemotherapy group (31% vs. 24%), a higher proportion of radical surgery (83% vs. 75%), shorter median operation time (185 minutes vs. 214 minutes), a higher rate of minimally invasive surgery (30% vs. 22%), a higher proportion receiving lobectomy (which preserves more lung function compared to pneumonectomy) (77% vs. 61%), and a higher proportion achieving R0 resection (i.e., complete tumor removal, 83% vs. 78%).

"At present, lung cancer remains the malignant tumor with the highest incidence and mortality in China."^[2]For patients with resectable NSCLC, surgery is the preferred treatment option that offers the potential for a cure; neoadjuvant therapy before surgery can shrink tumors, reduce surgical difficulty, and lower the risk of recurrence, increasing the chances of a cure. However, traditional neoadjuvant chemotherapy provides limited benefits to patients, and the risk of postoperative recurrence remains high, making it difficult to meet clinical needs.CheckMate -816Member of the Global Research Steering Committee, Principal Investigator in China, and Professor Wang Changli, Director of the Lung Cancer Center at Tianjin Medical University Cancer Institute and Hospital, stated,"Against this backdrop, the groundbreaking CheckMate -816 study has provided the first confirmation that neoadjuvant immunotherapy based on nivolumab demonstrates significantly superior overall efficacy across multiple levels compared to previous standards. At the same time, three cycles of neoadjuvant therapy are clinically easy to implement without affecting the timing or feasibility of surgery, increasing surgical difficulty, and are expected to bring more downstaging, R0 resection, and minimally invasive treatment opportunities for patients while preserving more lung function, meeting the needs of clinical practice. This achievement is expected to establish a new standard for the comprehensive surgical treatment of NSCLC in China and lead the perioperative treatment of NSCLC fully into the era of immunotherapy."

In addition, the pre-specified first interim analysis showed that recipientsOpdivoPatients treated with combination chemotherapy showed an encouraging trend in overall survival (OS), with a 43% reduction in the risk of death compared to chemotherapy alone.

In the study,OpdivoNeoadjuvant therapy with combination chemotherapy did not reveal new safety signals, with the incidence of grade 3-4 treatment-related adverse events and grade 3-4 surgical complications (33.5% and 11.4%, respectively) comparable to those of chemotherapy alone (36.9% and 14.8%, respectively).^[1], without increasing serious adverse events^[1]。

Based on the results of CheckMate -816, the neoadjuvant treatment regimen of nivolumab combined with chemotherapy has been included in the Clinical Application Guidelines for Immune Checkpoint Inhibitors by the Chinese Society of Clinical Oncology (CSCO).^[3], National Comprehensive Cancer Network (NCCN) Guidelines for the Diagnosis and Treatment of Non-Small Cell Lung Cancer^[4]Included in the recommendation, becoming the only currently recommended neoadjuvant immunotherapy for NSCLC in the aforementioned guidelines.

"In recent years, the timing of immunotherapy application has been continuously 'moved forward'; preoperative patients often have better physical conditions, a more intact immune system, and the presence of tumor antigens may activate stronger anti-tumor immune responses. Therefore, neoadjuvant immunotherapy is scientifically reasonable. The CheckMate -816 study was the first to confirm this concept in the NSCLC field, bringing it into reality, thus having milestone significance."CheckMate -816Professor Lu Shun, Director of the Oncology Department at Shanghai Chest Hospital affiliated with Shanghai Jiao Tong University and member of the Global Research Steering Committee, stated,"Data show that the combination of nivolumab and chemotherapy not only provides significant benefits in terms of short-term pCR rates and medium to long-term EFS, with a wide range of beneficiaries, but also shows a trend of greater benefit among Asian patients. Additionally, the study has achieved encouraging results in longer-term OS, which is expected to address the current clinical challenge of postoperative recurrence and metastasis, offering long-term survival benefits. Moreover, the favorable overall safety profile gives clinicians ample confidence. It is anticipated that this cutting-edge regimen will be widely implemented in China in the future, promoting the development of multidisciplinary comprehensive treatment models for lung cancer in China and benefiting more patients."

"This timeOpdivo"The approval of the new indication has, for the first time, advanced the application of immunotherapy for lung cancer — the most prevalent cancer type in China — to the neoadjuvant stage. This fully demonstrates Bristol-Myers Squibb's commitment to addressing unmet patient needs and its determination to continuously explore the use of immunotherapy for early-stage cancers under the drive of the 'China 2030 Strategy.'"Ms. Chen Siyuan, Vice President of Bristol-Myers Squibb, General Manager of China and Asian Regional Markets, and President of Bristol-Myers Squibb ChinaSaid, "OpdivoIt is currently the only immuno-oncology drug approved in China for two perioperative indications in early-stage tumors, demonstrating Bristol-Myers Squibb's innovative leadership in the field of early-stage cancer immunotherapy. Looking ahead, we will benefit more patients with cutting-edge scientific innovations; and work closely with all sectors of society to improve treatment accessibility and transform patient lives.

OpdivoTwo indications for adjuvant or neoadjuvant treatment of early-stage tumors have been approved in China, covering esophageal cancer or gastroesophageal junction cancer and non-small cell lung cancer. In the future, Bristol-Myers Squibb will further explore the application of immunotherapy in the field of early tumor treatment, as well as its combination with various treatment methods, to benefit a wider patient population.

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