Researchers reported the latest data from the phase Ib KEYNOTE-001 clinical trial at ASCO 2019.
CHICAGO-Pembrolizumab appears to be safe and effective and may substantially increase overall survival (OS) in patients with advanced non–small-cell lung cancer (NSCLC), according to the latest data from the phase Ib KEYNOTE-001 clinical trial (abstract LBA9015) presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 31–June 4 in Chicago.
Researchers found that 23.2% of patients who had not previously been treated with chemotherapy and 15.5% of previously treated patients were alive after 5 years. The greatest benefits were observed in patients with higher programmed death ligand 1 (PD-L1) expression.
The study showed that pembrolizumab quadrupled pre-immunotherapy era 5-year survival rates for patients when used as initial therapy (23.2% vs 5.5 %). This is the longest follow-up study to date of patients with advanced NSCLC treated with pembrolizumab, said lead study author Edward B. Garon, MD, an associate professor of medicine at UCLA, Los Angeles, California.
The fact that some patients on this trial are still alive after 7 years is quite remarkable, said Garon. He added that most patients who are doing well after 2 years on pembrolizumab live for 5 years or longer. “Five years survival is, of course, a benchmark that has typically been used in cancer, and it is certainly encouraging to have seen over 15% achieve 5-year survival in this group,” said Garon.
The KEYNOTE-001 study involved 550 patients with advanced NSCLC, including 101 treatment-naive patients and 449 patients who had received prior treatment. All patients received 2 mg/kg of their body weight of pembrolizumab every 3 weeks or 10 mg/kg every 2 or 3 weeks. The researchers found 18% (100 patients) were still alive after a median follow-up of 60.6 months.
Not surprisingly, higher levels of PD-L1 expression predicted longer survival. In treatment-naive patients, 29.6% with PD-L1 expression of 50% or more were alive after 5 years compared with 15.7% with expression levels below 50%. In previously treated patients, 25% who had PD-L1 expression levels of 50% or more were alive after 5 years compared with 12.6% with expression levels between 1% to 49%. The researchers found that only 3.5% of patients with expression levels below 1% were alive after 5 years.
Among patients receiving pembrolizumab after previous treatment, 42% had responses that lasted for a median of 16.8 months. For treatment-naÃ¯ve patients, pembrolizumab as initial therapy produced responses in 23% of patients that lasted a median of 38.9 months. Among the 60 patients who received ≥ 2 years of pembrolizumab treatment, 60 received ≥ 2 years of treatment (14 treatment-naÃ¯ve patients and 46 previously treated), more than 85% had an objective response, and the 5-year OS rate exceeded 75%, said Garon.
The most common side effect was hypothyroidism and the most serious side effect was pneumonitis. Immune-mediated adverse effects occurred in 17% of patients at 5 years, which the researchers report was similar to the incidence reported at a 3-year follow-up. “The safety data do not really show any late toxicity, which I consider encouraging,” said Garon.
The results of this study validate the clinical benefits of immunotherapy with a checkpoint inhibitor in advanced NSCLC, Francisco Robert, MD, a professor in the UAB Division of Hematology and Oncology and senior scientist at the O’Neal Comprehensive Cancer Center at UAB, Birmingham, Alabama, told Cancer Network.
“The current analysis of this study is a proof of principle of the long-term survival that can be seen in advanced NSCLC, contrary to what chemotherapy has shown. In addition, this study demonstrates the value of PD-L1 as a predictor of clinical benefits with checkpoint inhibitors,” Francisco said.
Pembrolizumab was first approved by the US Food and Drug Administration for advanced melanoma in September 2014 and for advanced NSCLC in October 2015. This past April, pembrolizumab received an expanded approval as front-line therapy for patients with stage III NSCLC who cannot have tumors surgically removed or irradiated, and for those with advanced NSCLC with PD-L1 expression levels over 1% and no EGFR or ALK gene mutations.