Long-Term Data Show Consistent OS Benefit With Nivolumab Plus Ipilimumab in mNSCLC

Nivolumab (Opdivo) plus ipilimumab (Yervoy) continues to show consistent, long-term survival benefits as a first-line treatment for metastatic non–small cell lung cancer (mNSCLC) compared with chemotherapy, according to updated results from part 1 of the phase 3 CheckMate-227 trial (NCT02477826) presented at the 2023 World Conference on Lung Cancer.¹

The combination demonstrated durable survival benefits regardless of PD-L1 expression levels at a minimum follow-up of more than 6 years (73.5 months), marking the longest reported follow-up in a phase 3 trial of immunotherapy for mNSCLC, according to a news release from Bristol Myers Squibb, manufacturer of both drugs.²

The primary end point population included patients with stage IV or recurrent, treatment-naïve NSCLC PD-L1 expression of 1% or higher with no known epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor mutations. This patient population was randomly assigned to receive nivolumab plus ipilimumab, nivolumab, or chemotherapy. Those whose tumors had a PD-L1 burden of 1% or less were randomized to receive nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy.

Lung cancer illustration | Image credit: SciePro - stock.adobe.com

The updated analysis included assessments of overall survival (OS), progression-free survival (PFS), overall response rate (ORR), duration of response (DOR), and OS by best response and reduction of tumor burden from baseline. Participants were stratified into the following groups for the OS by best response analysis: complete response (CR) or partial response (PR) with an 80% or greater tumor burden reduction, PR with 50% to less than 80% reduction, PR with 30% to less than 50% reduction, and nonresponders with stable or progressive disease. Baseline health-related quality of life (HRQOL) was also assessed using the EQ-5D-3L, with higher scores demonstrating better HRQOL.

In the primary end point population, 6-year survival on the immunotherapy combination was 22%, compared with 13% in the chemotherapy cohort (HR, 0.78; 95% CI, 0.67-0.91). An exploratory analysis of patients with tumors showing low PD-L1 expression found that 16% of patients treated with nivolumab plus ipilimumab were alive at 6 years, compared with 5% of patients treated with chemotherapy (HR, 0.65; 95% CI, 0.52-0.81).

Among treatment responders, greater proportions of both patients with PD-L1–high and PD-L1–low tumors experienced tumor burden reductions of 80% or more when treated with the immunotherapy combination (15% and 8%, respectively) vs chemotherapy (3% and 1%, respectively). The 6-year OS rate among patients with tumors expressing PD-L1 and who experienced a tumor burden reduction of 80% or greater was 59%, compared with 42% in the chemotherapy group. Among patients whose tumors had low PD-L1 expression of less than 1%, OS at 6 years was 77% in the nivolumab plus ipilimumab group bs 0% in the chemotherapy group.

Regarding safety, the updated results showed a consistent profile with previously reported data on the immunotherapy combination, and no new safety signals were identified.

Combination nivolumab and ipilimumab is FDA approved for the first-line treatment of mNSCLC in patients whose tumors express PD-L1 (≥1%), as determined by an FDA-approved test, and who do not show EGFR or ALK genomic tumor aberrations.³

“Immunotherapy has transformed the treatment of advanced lung cancer, and thankfully, a diagnosis no longer means the same thing as it used to for many patients. With these six-year results, we are seeing remarkably sustained and durable clinical survival benefits with nivolumab plus ipilimumab year-over-year,” Solange Peters, MD, PhD, professor and chair of medical oncology and the thoracic malignancies program in the Department of Oncology at the University Hospital of Lausanne in Lausanne, Switzerland, said in a statement.² “The long-term efficacy seen with the dual immunotherapy regimen in CheckMate-227 reinforce the importance of nivolumab plus ipilimumab to transform outcomes for appropriate patients with metastatic non-small cell lung cancer.”

References

1. Ramalingam SS, Ciuleanu TE, Caro RB, et al. Six-year survival and HRQoL outcomes with 1L nivolumab + ipilimumab in patients with metastatic NSCLC from CheckMate227. Presented at: International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer; September 9-12, 2023; Singapore. Abstract OA14.03. Accessed September 12, 2023. https://cattendee.abstractsonline.com/meeting/10925/Session/106

2. Six-year outcomes from phase 3 CheckMate -227 trial show durable, long-term survival with Opdivo (nivolumab) plus Yervoy (ipilimumab) in the first-line treatment of patients with metastatic non-small cell lung cancer. News release. Bristol Myers Squibb. September 11, 2023. Accessed September 12, 2023. https://news.bms.com/news/corporate-financial/2023/Six-Year-Outcomes-from-Phase-3-CheckMate--227-Trial-Show-Durable-Long-Term-Survival-with-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-in-the-First-Line-Treatment-of-Patients-with-Metastatic-Non-Small-Cell-Lung-Cancer/default.aspx

3. FDA approves nivolumab plus ipilimumab for first-line mNSCLC (PD-L1 tumor expression ≥1%). News release. FDA. May 15, 2020. Accessed September 11, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-plus-ipilimumab-first-line-mnsclc-pd-l1-tumor-expression-1