FDA Approves Opdivo® (nivolumab) Plus Chemotherapy as the First Neoadjuvant Immunotherapy for Resectable Non-Small Cell Lung Cancer

News on March 20, 2022 /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the U.S. Food and Drug Administration (FDA) has approved the anti-PD-1 therapy Opdivo (nivolumab) 360mg (intravenous formulation) in combination with platinum-based doublet chemotherapy, administered once every 3 weeks for a total of 3 cycles, for neoadjuvant (preoperative) treatment of resectable (Tumor≥4 cm or lymph node-positive) non-small cell lung cancer (NSCLC) adult patients, regardless of PD-L1 status.

It is worth mentioning that,Opdivo + Chemotherapy Marks the First and Only Immunotherapy-Based Treatment Option for NSCLC Preoperative Therapy.Previously, the immunotherapy combination regimen based on Opdivo has been approved for the treatment of metastatic and early-stage NSCLC.

This approval is based on the results of the pivotal Phase 3 CheckMate-816 trial (NCT02998528), the first Phase 3 trial to show positive results for immunotherapy in the neoadjuvant treatment of NSCLC. The data showed,In patients with resectable IB-IIIA stage NSCLC, compared with chemotherapy alone, Opdivo plus chemotherapy significantly improved event-free survival (EFS) and pathological complete response rate (pCR).

CheckMate-816 is a randomized, open-label, multicenter trial conducted in patients with resectable IB-IIIA stage NSCLC, regardless of PD-L1 expression status. In the trial, patients were randomly assigned to receive either Opdivo plus chemotherapy (once every 3 weeks for a total of 3 cycles) or chemotherapy alone (once every 3 weeks for a total of 3 cycles) as neoadjuvant (pre-surgery) treatment, followed by surgery. The primary endpoints of the trial are pathological complete response (pCR) and event-free survival (EFS). pCR is defined as no evidence of cancer cells in the resected tissue based on blinded independent pathological review. EFS is defined as the length of time without disease progression or recurrence.

The results showed that when used for neoadjuvant (preoperative) treatment, compared with the chemotherapy group, the Opdivo + chemotherapy group achieved statistically significant and clinically meaningful improvement in EFS, with a significant 37% reduction in the risk of disease progression, recurrence, or death (HR=0.63; 95% CI: 0.45-0.87; p=0.0052). The median EFS was 31.6 months in the Opdivo + chemotherapy group and 20.8 months in the chemotherapy group.

In addition, compared with the chemotherapy group, the pCR in the Opdivo + chemotherapy group significantly improved. Among patients who received Opdivo + chemotherapy treatment before surgery, 24% achieved pCR, while the proportion in the chemotherapy group was only 2.2% (estimated treatment difference 21.6; 95% CI: 15.1-28.2; p<0.0001). Moreover, the Opdivo + chemotherapy regimen was well tolerated, showing consistent improvement in pCR regardless of PD-L1 expression level, histology, or disease stage. A pre-specified interim analysis of overall survival (OS) showed an HR of 0.57 (95% CI: 0.38-0.87), but it was not statistically significant.

Mechanism of Action of Opdivo (Source: ono-pharma.com)

Lung cancer is the leading cause of cancer death worldwide. The two main types of lung cancer are non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is the most common type of lung cancer, accounting for 84% of lung cancer diagnoses. Non-metastatic cases account for NSCLC.DiagnosisThe majority (approximately 60%). Although many patients with non-metastatic NSCLC are cured by surgery, 30%-55% of patients still experience recurrence and die from the disease after surgical resection. Therefore, treatment regimens are needed before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.

Currently, in early-stage NSCLC, Bristol-Myers Squibb and its collaborators are exploring the application of immunotherapy in neoadjuvant treatment, adjuvant treatment, perioperative treatment, as well as in combination with chemoradiotherapy. The scientific rationale for using immunotherapy in the neoadjuvant setting has two aspects: (1) It provides the earliest opportunity to treat cancer cells that have spread throughout the body without being detected (occult metastases); (2) The presence of a tumor during immunotherapy may elicit a stronger immune response, potentially enhancing the effect on the primary tumor.TumorMore effective.

Opdivo belongs to PD-(L)1 tumor immunotherapy, which aims to use the body's own immune system to fight cancer by blocking the PD-1/PD-L1 signaling pathway to cause cancer cell death, having the potential to treat various types.Tumorpotential. As of now, Opdivo has been approved for various cancer indications worldwide.

In China, Opdivo (Ou Di Wo) was approved for marketing in June 2018, becoming the first immunotherapy drug approved in the Chinese market.Tumor(I-O) therapeutic drugs, which have been approved for multiple indications, see details《OpdIVO (Nivolumab Injection Instructions).(Bioon.com)

Source of the original text:U.S. Food and Drug Administration Approves Opdivo® (nivolumab) with Chemotherapy as Neoadjuvant Treatment for Certain Adult Patients with Resectable Non-Small Cell Lung Cancer