Introduction

In an exciting update for the oncology community, the five-year data from the CheckMate 9LA trial shows that the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) dramatically improves survival rates in patients with stage IV non–small cell lung cancer (NSCLC). This regimen stands out for patients who have had no prior systemic therapy and carry no actionable driver mutations.

Subgroup Analysis

Subgroup analysis from the study highlights the distinct PD-L1 expression levels among participants. Approximately one-third had PD-L1 levels below 1%, while others were distributed between levels of 1% to 49% and 50% or greater. Notably, over half of the participants demonstrated a non-squamous histology type.

Treatment Methods

Patients were randomly assigned to receive either the dual immunotherapy or a benchmark chemotherapy regimen consisting of two cycles of chemotherapy and two cycles of nivolumab/ipilimumab. The rationale for combining a short chemotherapy course with immunotherapy is to potentially enhance early treatment responses, a significant concern during the initial treatment phase.

Results of the Trial

The trial's primary endpoint, overall survival (OS), showed a striking 5-year median OS of 15.8 months for those receiving the combined regimen, compared to 11.0 months for traditional chemotherapy. The overall survival percentages illuminated by the trial were equally compelling: 18% for the combination therapy group versus 11% for chemotherapy alone.

Impact on PD-L1 Negative Population

An unexpected outcome arose from the traditionally hard-to-treat PD-L1 negative population, which showcased a median OS of 17.7 months when supported by the combination therapy, compared to just 9.8 months with chemotherapy. The 5-year survival rates for the PD-L1 negative cohort reached 22%, significantly higher than the historical benchmark of 8%.

Overall Benefit Across Populations

Both squamous and non-squamous populations benefited from the combination therapy, with the squamous group showing a 5-year OS rate of 18% as opposed to only 7% for chemotherapy, underscoring the broader applicability of this treatment strategy.

Adverse Events and Survival

Surprisingly, even patients who experienced treatment-related adverse events (AEs) maintained promising survival statistics, marking a noteworthy finding from the CheckMate 9LA trial. Common AEs included skin reactions and pneumonitis, though these were predominantly mild (grade 1 and 2). Importantly, 41% of patients had to discontinue treatment due to these side effects; however, even after stopping the regimen, many continued to derive benefits with an impressive median duration of response (DOR) of 14.5 months.

Patients with Brain Metastases

Patients with underlying brain metastases, a notoriously challenging group, also benefitted from the regimen. The results showed a striking survival rate of 16% after 3 years for those receiving the combination therapy, in comparison to just 6% for those with brain metastases receiving chemotherapy alone.

Conclusion

The insights gathered from the CheckMate 9LA trial reinforce the potential for nivolumab and ipilimumab combinations to offer effective treatment alternatives for NSCLC patients, particularly in high-risk groups. As more data emerges, this regimen may become a foundational component of lung cancer treatment protocols, helping to expand options and improve outcomes for thousands of patients worldwide.

Future Outlook

Stay tuned for more updates as new breakthroughs in cancer therapy continue to emerge!