Neoadjuvant Nivolumab/Chemo Wins EU Approval for Resectable PD-L1+ NSCLC

The European Commission (EC) has approved nivolumab (Opdivo) in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable non–small cell lung cancer (NSCLC) at high risk of recurrence with tumor cell PD-L1 expression of at least 1%.¹

The regulatory decision was supported by data from the phase 3 CheckMate 816 trial (NCT02998528), which showed that nivolumab plus chemotherapy produced a statistically significant and clinically meaningful improvement in event-free survival (EFS) and pathologic complete response (pCR) compared with neoadjuvant chemotherapy alone.

The median EFS for patients in the nivolumab arm was 31.6 months vs 20.8 months for patients treated with chemotherapy alone (HR, 0.63; 97.38% CI, 0.43-0.91; P = .0052). Additionally, the pCR rate was 24% for nivolumab/chemotherapy vs 2.2% for chemotherapy alone (HR, 13.9; 99% CI, 3.49- 55.75; P < .0001). Furthermore, nivolumab/chemotherapy led to a 43% reduction in the risk of death vs chemotherapy alone (HR, 0.57; 99.67% CI, 0.30-1.07).

Nivolumab plus chemotherapy is the first neoadjuvant immunotherapy-based treatment regimen approved for patients in the European Union (EU) in this setting.

“While cure is possible for some patients with resectable NSCLC via surgery, approximately 30% to 55% of the patients who have their tumors removed will eventually experience recurrence and ultimately die from their disease, thus creating a strong need for treatment options beyond surgery that can help prevent recurrence,” Nicolas Girard, MD, a professor of thoracic oncology at the Institut Curie and Paris Saclay University, stated in a news release. “The importance of the approval of nivolumab combined with chemotherapy for the treatment of certain patients with non-metastatic NSCLC in the EU cannot be overstated—it presents the opportunity to change the way their cancer is treated and offers a solution that may reduce the risk of their cancer returning after surgery.”

Previously, in March 2022, the FDA approved nivolumab plus platinum-doublet chemotherapy for adult patients with resectable NSCLC in the neoadjuvant setting, based on data from CheckMate 816.²

CheckMate 816 was an open-label, multicenter trial that enrolled patients with newly diagnosed, resectable, stage IB to IIIA NSCLC. Patients were required to have an ECOG performance status of 0 or 1.³

Key exclusion criteria included the presence of locally advanced, inoperable, or metastatic disease; active, known, or suspected autoimmune disease; or prior treatment with any drug targeting T-cell co-stimulations pathways, such as checkpoint inhibitors.

For the primary analysis, 358 patients were randomly assigned 1:1 to receive 360 mg of nivolumab plus platinum-doublet chemotherapy once every 3 weeks for 3 cycles or chemotherapy alone, followed by surgery.¹

EFS and pCR served as the co-primary end points, irrespective of PD-L1 expression. Key secondary end points included major pathological response, OS, and time to death or distant metastases.

Regarding safety, pooled data from patients with various tumor types treated with nivolumab plus chemotherapy (n = 1268), the most frequent adverse effects reported in at least 10% of patients included nausea (51%), peripheral neuropathy (39%), fatigue (39%), diarrhea (33%), decreased appetite (33%), constipation (31%), vomiting (27%), stomatitis (22%), abdominal pain (21%), rash (18%), pyrexia (17%), musculoskeletal pain (16%), cough (13%), oedema, including peripheral oedema (12%), and hypoalbuminemia (11%).

References

1. Bristol Myers Squibb receives European Commission approval for Opdivo (nivolumab) with chemotherapy as neoadjuvant treatment of resectable non-small cell lung cancer at high risk of recurrence in patients with tumor cell PD-L1 expression ≥1%. News release. Bristol Myers Squibb. June 29, 2023. Accessed June 29, 2023. https://news.bms.com/news/corporate-financial/2023/
2. FDA approves neoadjuvant nivolumab and platinum-doublet chemotherapy for early-stage non-small cell lung cancer. News release. FDA. March 4, 2022. Accessed June 29, 2023. 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 June 5, 2023. Accessed June 29, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT02998528