Neoadjuvant Nivolumab Plus Chemo Improves OS in Resectable NSCLC

Neoadjuvant treatment with nivolumab (Opdivo) in combination with platinum-doublet chemotherapy led to statistically significant and clinically meaningful improvement in overall survival (OS) vs neoadjuvant chemotherapy alone in patients with resectable (tumors ≥4 cm or node positive) non–small cell lung cancer (NSCLC), according to updated data from the phase 3 CheckMate 816 trial (NCT02998528).1

Safety data for the combination of nivolumab and chemotherapy were consistent with data from previous studies, and no new safety signals were identified.

In a news release from Bristol Myers Squibb, the company announced it is currently analyzing the updated findings and will provide a full update in a future peer-reviewed setting.

“The final analysis of OS in the CheckMate 816 study underscores the potential of [nivolumab] in combination with chemotherapy to provide a meaningful survival benefit for patients with resectable NSCLC,” Dana Walker, MD, MSCE, vice president, global program lead, late development, oncology, Bristol Myers Squibb, stated in a news release. “This is the first and only phase 3 study of a neoadjuvant-only immuno-oncology therapy to show a statistically significant benefit in patients with resectable NSCLC. [Nivolumab]-based therapies have shown improved efficacy in the neoadjuvant and perioperative treatment of patients with resectable NSCLC.”

In March 2022, the FDA approved nivolumab plus platinum-doublet chemotherapy for the neoadjuvant treatment of adult patients with resectable NSCLC, based on previously reported data from CheckMate 816.2

Prior data supporting the approval showed that patients treated with the nivolumab regimen experienced a median event-free survival (EFS) of 31.6 months (95% CI, 30.2-not reached) compared with 20.8 months (95% CI, 14.0-26.7) for those given chemotherapy alone (HR, 0.63; 97.38% CI, 0.43-0.91; P = .0052). Additionally, nivolumab plus chemotherapy generated a pathological complete response (pCR) rate of 24% (95% CI, 18.0%-31.0%) vs 2.2% (95% CI, 0.6%-5.6%) for chemotherapy alone.

The randomized, open-label study enrolled patients at least 18 years of age with stage IB to IIIA, resectable NSCLC who had adequate lung function capacity to tolerate surgery.3 Other key inclusion criteria consisted of an ECOG performance status of 0 or 1, along with available tumor tissue from the primary lung tumor. Patients were allowed to enroll irrespective of PD-L1 status.1

Patients were excluded if they had evidence of locally advanced, inoperable or metastatic disease; had active, known or suspected autoimmune disease; or received prior treatment with any drug targeting T-cell co-stimulations pathways, such as immune checkpoint inhibitors.3

During the study, 358 patients were randomly assigned to receive either nivolumab at 360 mg plus histology-based platinum-doublet chemotherapy once every 3 weeks for 3 cycles before surgery; or platinum-doublet chemotherapy once every 3 weeks for 3 cycles, followed by surgery.1

EFS and pCR rate served as the trial’s dual primary end points.3 Secondary end points comprised major pathologic response rate, OS, and time to death or distant metastases.

Safety data reported at the time of the approval of the combination showed that the most common adverse effects reported in at least 20% of patients treated with nivolumab plus chemotherapy included nausea, constipation, fatigue, decreased appetite, and rash.2

Delays or cancellations of surgery were not increased in the experimental arm compared with the control arm. Notably, the median duration of hospital stays after definitive surgery and the rates of AEs deemed surgical complications were similar between the two arms.

The recommended dose of the combination is nivolumab at 360 mg in combination with platinum-doublet chemotherapy once every 3 weeks for 3 cycles.

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/corporate-financial/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. FDA approves neoadjuvant nivolumab and platinum-doublet chemotherapy for early-stage non-small cell lung cancer. FDA. March 4, 2022. Accessed February 19, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-neoadjuvant-nivolumab-and-platinum-doublet-chemotherapy-early-stage-non-small-cell-lung
3. 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