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2019 ASCO: KEYNOTE-001: 5-Year Survival Data for Patients With Advanced NSCLC Treated With Pembrolizumab

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Key Points

  • In treatment-naive patients, 29.6% with PD-L1 expression of 50% or more were alive after 5 years, compared with 15.7% with PD-L1 expression levels below 50%.
  • In patients who had received previous treatment, 25% who had PD-L1 expression levels of 50% or more were alive after 5 years, compared with 12.6% with PD-L1 expression levels between 1% and 49%. Only 3.5% of people with PD-L1 expression levels below 1% were alive after 5 years.
  • Among patients receiving pembrolizumab after undergoing previous treatment, 42% had responses that lasted for a median of 16.8 months. For those who received pembrolizumab as initial therapy, 23% had responses that lasted a median of 38.9 months.

Five-year data from the phase Ib KEYNOTE-001 trial showed that treatment with pembrolizumab was safe and effective and substantially increased overall survival in patients with advanced non–small cell lung cancer (NSCLC). Specifically, 23.2% of people who had not previously been treated with chemotherapy and 15.5% of previously treated patients were alive after 5 years, with the greatest benefit observed in patients with higher programmed cell death ligand 1 (PD-L1) expression. According to the trial researchers, KEYNOTE-001 is the longest follow-up study to date of people with advanced NSCLC treated with pembrolizumab. The study was presented by Garon et al at the 2019 ASCO Annual Meeting (Abstract LBA9015) and is in press with the Journal of Clinical Oncology.

“The uniformly negative outlook that has been associated with a diagnosis of advanced NSCLC is certainly no longer appropriate,” said lead study author Edward B. Garon, MD, MS, Associate Professor of Medicine at the University of California, Los Angeles. “The fact that we have patients on this trial [who] are still alive after 7 years is quite remarkable. We also have evidence that most patients who are doing well after 2 years on pembrolizumab live for 5 years or more.”

Study Methods

In 2011, when KEYNOTE-001 began enrollment, immunotherapy treatments were not widely available, so most participants had previously been treated with systemic medicines or targeted therapies. There were 550 patients with advanced NSCLC in the trial, including 101 patients who were treatment-naive 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. In recent years, however, the protocol was changed to a single dose of 200 mg—regardless of body weight—every 3 weeks, the typical regimen in clinical practice.

Results

Patients were followed for a median of 60.6 months. At that point, 18% of enrollees (100 participants) were still alive. Of those who were treatment-naive, 23% were still alive after 5 years, compared with 15.5% of those previously treated. Researchers observed that higher levels of PD-L1 expression predicted longest survival. Specifically:

  • In treatment-naive patients, 29.6% with PD-L1 expression of 50% or more were alive after 5 years, compared with 15.7% with PD-L1 expression levels below 50%.
  • In patients who had received previous treatment, 25% who had PD-L1 expression levels of 50% or more were alive after 5 years, compared with 12.6% with PD-L1 expression levels between 1% and 49%. Only 3.5% of people with PD-L1 expression levels below 1% were alive after 5 years.

Among patients receiving pembrolizumab after undergoing previous treatment, 42% had responses that lasted for a median of 16.8 months. For those who received pembrolizumab as initial therapy, 23% had responses that lasted a median of 38.9 months.

Immune-related toxic side effects occurred in 17% of enrollees. The most common side effect was hypothyroidism, and the most serious side effect seen was pneumonitis.

Next Steps

Dr. Garon noted that the researchers will try refining their understanding of which patients received the most benefit from pembrolizumab, as well as identifying impediments that prevent the immune system from destroying tumors so that these mechanisms could also be combatted. The investigators hope to explore possible combination therapies of pembrolizumab with conventional or other immunotherapies.

Disclosure: This study received funding from Merck Sharp & Dohme Corp. For full disclosures of the study authors, visit coi.asco.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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