Neoadjuvant/chemo nivolumab 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 PD-L1 expression in cells tumors of at least 1%.¹

The regulatory decision was supported by data from the Phase 3 CheckMate 816 study (NCT02998528), which showed that nivolumab plus chemotherapy resulted in a statistically significant and clinically meaningful improvement in event-free survival (EFS) and complete pathological 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 receiving chemotherapy alone (HR, 0.63; 97.38% CI, 0.43-0.91 ; P = .0052). Additionally, the pCR rate was 24% for nivolumab/chemotherapy versus 2.2% for chemotherapy alone (HR, 13.9; 99% CI, 3.49-55.75; P < .0001). Additionally, nivolumab/chemotherapy resulted in a 43% reduction in the risk of death compared with 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 surgically resectable NSCLC, approximately 30% to 55% of patients who have their tumors removed will eventually experience a recurrence and eventually die of the disease, thus creating a strong need for Treatment options besides surgery that can help prevent recurrences, Nicolas Girard, MD, professor of thoracic oncology at the Institut Curie and Paris Saclay University, said in a news release. The importance of the approval of nivolumab in combination with chemotherapy for the treatment of some patients with non-metastatic NSCLC in the EU cannot be overstated – it offers an opportunity to change the way their cancer is treated and offers a solution which can reduce the risk of cancer returning after surgery.

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

CheckMate 816 was an open-label, multicenter study 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

The main exclusion criteria included the presence of locally advanced, inoperable, or metastatic disease; known or suspected active autoimmune disease; or previous treatment with any drugs that target T-cell constimulatory pathways, such as checkpoint inhibitors.

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

EFS and pCR served as co-primary endpoints, independent of PD-L1 expression. Key secondary endpoints included primary disease response, OS, and time to death or distant metastasis.

In the safety pooled data from patients with various cancer 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 rash (18%), pyrexia (17%), musculoskeletal pain (16%), cough (13%), edema including peripheral edema (12%) and hypoalbuminaemia (11%).

References

1. Bristol Myers Squibb receives European Commission approval for Opdivo (nivolumab) with chemotherapy as the neoadjuvant treatment of resectable non-small cell lung cancer at high risk of recurrence in patients with 1% PD-L1 expression on tumor cells. Press release. Bristol Myers Squibb. June 29, 2023. Accessed June 29, 2023. https://news.bms.com/news/corporate-financial/2023/
2. FDA approves neoadjuvant chemotherapy with nivolumab and platinum doublet for early-stage non-small cell lung cancer Press 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 -lung not small cell
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