Prolonged survival possible with pembrolizumab in advanced NSCLC
medwireNews: Updated results from the phase Ib KEYNOTE-001 trial suggest that some individuals with advanced non-small-cell lung cancer (NSCLC) can achieve long-term survival with pembrolizumab monotherapy.
As reported in a poster at the 2019 ASCO Annual Meeting in Chicago, Illinois, USA, 23.2% of the 101 treatment-naïve patients with locally advanced or metastatic NSCLC were alive at 5 years after initiation of pembrolizumab, as were 15.5% of the 449 patients who had received at least one previous line of therapy.
These overall survival (OS) rates compare with a historical rate of 5.5% among individuals who received chemotherapy for distant metastases, said presenting author Edward Garon, from the University of California Los Angeles in the USA, at a press conference.
“The uniformly negative outlook that has been associated with a diagnosis of advanced non-small cell lung cancer is certainly no longer appropriate,” he told the press.
The benefit of pembrolizumab treatment – given at a dose of either 2 mg/kg every 3 weeks or 10 mg/kg every 2 or 3 weeks – appeared to be greatest in patients with high PD-L1 expression. Specifically, in the previously treated group, 5-year OS was 25.0% for those with a PD-L1 tumor proportion score (TPS) of at least 50%, while the rates were 12.6% and 3.5% for individuals with a PD-L1 score of 1–49% and less than 1%, respectively.
And among treatment-naïve patients, the 5-year rates were 29.6% and 15.7% for those with a TPS of at least 50% and 1–49%, respectively. As just 12 patients had a PD-L1 TPS below 1%, data were not reported for this subgroup.
Of note, just over three-quarters (76.7%) of the 60 patients who received pembrolizumab for 2 years or more were alive at data cutoff, which was at a median follow-up of 60.6 months. The 5-year OS rates were a comparable 78.6% and 75.8% for the treatment-naïve and previously treated groups, respectively.
The longer follow-up did not reveal any safety concerns, said Garon, noting that “late-onset toxicity, including immune-related toxicity, was rare.”
Seventeen percent of participants experienced an immune-related adverse event (irAE) of any grade, most commonly hypothyroidism, while pneumonitis was the most frequent irAE of grade 3 or higher.
In response to a question from medwireNews about biomarkers for immunotherapy, Garon said that “the best biomarker eventually is going to be a functional one, but that isn’t where we are yet.”
Although PD-L1 as a biomarker has its negatives, “it has persistently shown an ability to pick out patients who do better,” he added.
Garon said that “there is a great deal of interest” in the tumor mutational burden, but although the biomarker has predicted short-term outcomes “reasonably well,” robust results have not been seen for survival.
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