Credit: Sebastian Kaulitzki | stock.adobe.com
A final analysis of survival data from the Phase III CheckMate -816 trial (NCT02998528) showed a statistically significant benefit in overall survival (OS) among patients with resectable non-small cell lung cancer (NSCLC) administered neoadjuvant Opdivo (nivolumab; Bristol Myers Squibb) in combination with chemotherapy.1,2 Bristol Myers Squibb stated that the updated OS data will undergo a full analysis plans before being shared in a future peer reviewed publication.
“The final analysis of overall survival in the CheckMate -816 study underscores the potential of Opdivo in combination with chemotherapy to provide a meaningful survival benefit for patients with resectable NSCLC,” Dana Walker, MD, MSCE, vice president and global program lead, late development, oncology, Bristol Myers Squibb, said in a press release. “This is the first and only Phase III study of a neoadjuvant-only immuno-oncology therapy to show a statistically significant benefit in patients with resectable NSCLC. Opdivo -based therapies have shown improved efficacy in the neoadjuvant and perioperative treatment of patients with resectable NSCLC.”1
Opdivo is a monoclonal antibody that binds to the PD-1 receptor and inhibits tumor growth by improving T-cell function.3,4 Opdivo has been approved across an array of indications, both as a single agent and in combination therapy, including for patients with unresectable or metastatic melanoma; metastatic NSCLC; advanced renal cell carcinoma; classical Hodgkin lymphoma; recurrent or metastatic squamous cell carcinoma of the head and neck; locally advanced or metastatic urothelial carcinoma; microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer; and hepatocellular carcinoma.3
Trial Design
The randomized, open label, multi-center, Phase III CheckMate -816 trial analyzed Opdivo plus chemotherapy compared to chemotherapy alone in the neoadjuvant treatment of patients with resectable stage IB to IIIA NSCLC, regardless of PD-L1 expression. Patients with stage IB to IIIA resectable NSCLC were randomly assigned to receive Opdivo with platinum-based chemotherapy or platinum-based chemotherapy alone, followed by resection.
The trial’s primary endpoints were event-free survival (EFS) and pathological complete response as determined by blinded independent review. The trial’s key secondary endpoint was OS.
Data released in June 2024 show that at a median follow up of 57.6 months, neoadjuvant treatment with Opdivo plus chemotherapy produced a median EFS of 43.8 months compared to 18.4 months among patients in the chemotherapy alone cohort (HR, 0.66; 95% CI, 0.49 to 0.90).5
Rates of four-year EFS were 49% in the neoadjuvant Opdivo plus chemotherapy cohort compared with 38% in the chemotherapy alone cohort. At that time, OS had not yet reached statistical significance; however, the combination of neoadjuvant Opdivo plus chemotherapy continued demonstrating a clinically important OS improvement trend compared to chemotherapy alone (HR, 0.71; 98.36% CI, 0.47 to 1.07), which was reinforced by the updated findings.
In the June 2024 data release, 71% of patients administered neoadjuvant Opdivo plus chemotherapy were alive at the four-year mark compared to 58% of patients administered chemotherapy alone. There were no new safety signals reported among patients administered neoadjuvant Opdivo plus chemotherapy at the extended follow-up and no new safety signals were reported in the updated data.
References
1. Bristol Myers Squibb Announces Opdivo® Plus Chemotherapy as the First and Only Neoadjuvant-Only Immuno-Oncology Therapy to Demonstrate Statistically Significant and Clinically Meaningful Overall Survival in Resectable Non-Small Cell Lung Cancer. News release. Bristol Myers Squibb. February 19, 2025. Accessed February 19, 2025. https://news.bms.com/news/details/2025/Bristol-Myers-Squibb-Announces-Opdivo-Plus-Chemotherapy-as-the-First-and-Only-Neoadjuvant-Only-Immuno-Oncology-Therapy-to-Demonstrate-Statistically-Significant-and-Clinically-Meaningful-Overall-Survival-in-Resectable-Non-Small-Cell-Lung-Cancer/default.aspx
2. A Neoadjuvant Study of Nivolumab Plus Ipilimumab or Nivolumab Plus Chemotherapy Versus Chemotherapy Alone in Early Stage Non-Small Cell Lung Cancer (NSCLC) (CheckMate 816). ClinicalTrials.gov. Updated January 24, 2025. Accessed February 19, 2025. https://clinicaltrials.gov/study/NCT02998528
3. Opdivo. Prescribing information. Bristol Myers Squibb; 2021. Accessed February 19, 2025. https://packageinserts.bms.com/pi/pi_opdivo.pdf
4. FDA approves first immunotherapy for initial treatment of gastric cancer. News release. FDA. April 16, 2021. Accessed February 19, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer.
5. Bristol Myers Squibb Presents Multiple New Analyses at 2024 ASCO® Annual Meeting Highlighting Opdivo and Opdivo-based Combinations in Early and Advanced Stages of Non-Small Cell Lung Cancer. News release. Bristol Myers Squibb. June 3, 2024. Accessed February 19, 2025. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibb-Presents-Multiple-New-Analyses-at-2024-ASCO-Annual-Meeting-Highlighting-Opdivo-and-Opdivo-based-Combinations-in-Early-and-Advanced-Stages-of-Non-Small-Cell-Lung-Cancer/default.aspx