Neoadjuvant Nivolumab plus chemotherapy has significantly improved event-free survival in patients with resectable non-small cell lung cancer in CheckMate -816
The phase 3 CheckMate -816 trial has met the primary endpoint of improved event-free survival ( EFS ) in patients with resectable stage IB to IIIA non-small cell lung cancer ( NSCLC ).
In a prespecified interim analysis, Nivolumab ( Opdivo ) plus chemotherapy has shown a statistically significant and clinically meaningful improvement in EFS compared to chemotherapy alone when given before surgery.
This combination previously showed a significant improvement of pathologic complete response ( pCR ), the trial’s other primary endpoint.
The safety profile of Nivolumab plus chemotherapy was consistent with previously reported studies in NSCLC.
CheckMate -816 is the first phase 3 trial with an immunotherapy-based combination to demonstrate a statistically significant and clinically meaningful benefit as a neoadjuvant treatment for patients with non-metastatic non-small cell lung cancer.
The combination of Nivolumab plus chemotherapy first has shown a statistically significant improvement in pathologic complete response rate without impacting surgical outcomes and has now extended the time patients live free of disease progression, recurrence or death.
The event-free survival data from CheckMate -816 strengthen the evidence for the potential of Nivolumab-based therapies to improve long-term clinical outcomes when used in the earlier stages of non-metastatic cancers.
The scientific rationale for using immunotherapy in the neoadjuvant setting is twofold: the presence of a tumor during immunotherapy treatment may enable a stronger immune response, potentially making the treatment more effective against a primary tumor, while offering an opportunity to target covert micro-metastasis.
To date, Nivolumab has shown improved efficacy in the neoadjuvant or adjuvant treatment of four tumor types: lung cancer, bladder cancer, esophageal / gastroesophageal junction cancer and melanoma.
CheckMate -816 is a randomized, open label, multi-center trial evaluating Nivolumab plus chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable non-small cell lung cancer, regardless of PD-L1 expression.
For the primary analysis, 358 patients were randomized to receive either Nivolumab 360 mg plus histology-based Platinum doublet chemotherapy every three weeks for three doses, or Platinum doublet chemotherapy every three weeks for three doses, followed by surgery.
The primary endpoints of the trial are pathologic complete response and event-free survival. Secondary endpoints include overall survival ( OS ), major pathologic response ( MPR ), and time to death or distant metastases.
Lung cancer is the leading cause of cancer deaths globally.
The two main types of lung cancer are non-small cell and small cell.
Non-small cell lung cancer ( NSCLC ) is one of the most common types of lung cancer, representing up to 84% of diagnoses.
Non-metastatic cases account for the majority of NSCLC diagnoses ( approximately 60% ). While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery ( neoadjuvant ) and/or after surgery ( adjuvant ) to improve long-term outcomes.
Nivolumab is a programmed death-1 ( PD-1 ) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response.
In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. ( Xagena )
Source: Bristol Myers Squibb ( BMS ), 2021