Three-year results from the KEYNOTE-001 study on pembrolizumab in advanced non-small-cell lung cancer (NSCLC) confirm the known safety and efficacy data for the PD-1 inhibitor.
The study, published in The Lancet Respiratory Medicine, comprised 550 patients – about 18% of whom were treatment naïve and the rest had been previously treated.
An objective response was reported in 41% of treatment naïve patients and 23% of previously treated patients. The median time to response was 2·1 months in both groups with a duration of response of 16.7 months in the treatment naïve and 33 months in the previously treated group.
The proportion of responding patients with ongoing response at data cutoff was 46% in treatment naive patients and 63% in previously treated patients.
The 36-month survival estimates were 26·4% for treatment naive and 19·0% for previously treated patients.
The researchers, including Associate Professor Rina Hui from Westmead Hospital and the University of Sydney, said in the paper the 36-month survival among patients with PD-L1 tumour proportion score of 50% or greater in treatment naive and previously treated groups was ‘remarkable’ at over 25%.
“Consistent with the initial report from KEYNOTE-001, median overall survival was increased among patients with tumour proportion score of 50% or greater versus patients with tumour proportion score 1–49% or less than 1%.”
“Interestingly, although patients with higher PD-L1 expression are expected to have improved survival with pembrolizumab treatment, previously treated patients with tumour proportion score 1–49% seemed to have similar survival prevalence to those with tumour proportion score less than 1%.”
However they said the finding might have been influenced by confounding factors.
The study found the overall frequency of treatment-related toxicity, immune-mediated adverse events and infusion reactions was similar to that of previous reports. There was a low prevalence of treatment discontinuation and late-onset toxicity was uncommon.
“Together, these results provide the longest reported follow-up of pembrolizumab in advanced non-small-cell lung cancer so far, and support the safety and clinical tolerability of the drug in this setting.”
A Comment article in the journal said the findings were consistent with those from other studies of immune checkpoint inhibitors (ICI) nivolumab and atezolizumab.
“All these trials show that approximately one-fifth (17–23%) of the patients treated with ICI have long term benefit.”
“Nearly all long-term survivors had at least a partial response to ICI, with most responses occurring in the first months of treatment. Those with a high PD-L1 expression had the highest survival prevalence, but also some patients with low or negative PD-L1 levels survived 3 years or more.”
“In conclusion, monotherapy with ICI provides promising 3-year overall survival data in both previously untreated and previously treated patients with locally advanced or metastatic non-small-cell lung cancer, being most prevalent in responders and patients with a high PD-L1 TPS score.”