CheckMate 816 is a landmark phase III randomised study that assessed neoadjuvant chemotherapy plus nivolumab, which is an immune checkpoint inhibitor, versus chemotherapy alone in patients with resectable non-small cell lung cancer. These patients are usually treated with surgery, which is the mainstay of the treatment, but we know that the risk of recurrence is really high. Historically these patients receive adjuvant or neoadjuvant chemotherapy alone.
In CheckMate 816 358 patients with resectable non-small cell lung cancer, stage 1b-3a, were randomised to receive either neoadjuvant treatment with chemotherapy alone, this is the control arm, or the same chemotherapy plus nivolumab three cycles before going to surgery. Then they could receive adjuvant therapies depending on the findings and based on the investigator decision.
We presented at ELCC 2023 the updated results from this study. The study is positive and achieved its primary endpoint of pathological complete response – 24% with nivolumab plus chemotherapy versus 2% with chemotherapy alone – as well as EFS, event free survival, which was increased with the addition of nivolumab to chemotherapy. This was previously published in The New England Journal of Medicine.
Here we have one year additional follow-up and we are able to show updated EFS, updated overall survival, as well as some biomarker analysis and some subgroup analysis. The first result is that with this one year additional follow-up we still have durable benefit in terms of EFS in favour of nivolumab plus chemotherapy versus chemotherapy alone. The hazard ratio is 0.68 so we have a 32% decrease in the risk of disease progression or death after randomisation. At three years the EFS rate is 43% with chemotherapy alone and 57% with nivolumab plus chemotherapy.
Those are key findings, to me, that this benefit is observed across most key subgroups, including the subgroups based on surgical outcomes. We see this EFS benefit both in patients who have a thoracotomy, patients who have minimally invasive surgery. We see this benefit in patients who have a lobectomy, a pneumonectomy, so clearly the benefit is observed across all the patient subgroups.
We were also able to update overall survival. Still overall survival is not mature enough at this pre-specified second interim analysis. Still we have a tendency for overall survival benefit; the median is not reached in either arm. At three years we have an OS rate of 64% in the control arm, 78% in the nivolumab plus chemotherapy arm. This is a hazard ratio of 0.62, still not crossing the statistical boundary but we will continue to follow this cohort of patients.
We were also able to better understand the protective effect of the addition of nivolumab to chemotherapy in terms of risk of recurrence. It was striking to see a clear different in CNS recurrences which actually were observed in 13% of patients who received chemotherapy alone as neoadjuvant treatment versus 4% in the nivolumab plus chemotherapy arm.
So, this is clearly a study that is continuing. The follow-up of patients is continuing. We will see overall survival data becoming more major. This is already a standard of care – the addition of nivolumab to chemotherapy is standard of care in the setting of resectable non-small cell lung cancer. It is approved in many countries; it is implemented in routine practice. So clearly these data further reinforce this option, nivolumab plus chemotherapy as a standard of care before surgical resection of non-small cell lung cancer.