An example from a recent media investigation into the KEYNOTE-689 trial. This trial evaluated the efficacy and safety of pembrolizumab in previously treated patients with HNSCC. The trial’s results have ignited an intense debate among doctors about whether the current treatment standard should be altered. Interestingly, the fruit of that labor yielded both positive findings and red flags, with equally encouraging results as there were troubling adverse effects.
The trial included two cycles of neoadjuvant 200 mg pembrolizumab every three weeks, followed by surgery. Additionally, patients were treated with concurrent radiation therapy and with or without cisplatin before and with up to 12 cycles of maintenance pembrolizumab therapy. These treatment protocols were intended to measure the drug’s effect on tumor downstaging and resultant patient outcomes.
Efficacy Results from KEYNOTE-689
These results from the KEYNOTE-689 trial showed that pembrolizumab has the potential to impact treatment outcomes for patients with HNSCC across lines of therapy. In patients with a CPS of ≥ 10, the major pathologic response was 13.7%. For those with a CPS of ≥ 1, the response rate was 9.8% call rate at about a CPS of 5. In total, 9.3% of all patients had a pCR.
The authors found that patients with a CPS of 10 or greater had a meaningful treatment benefit from pembrolizumab. They experienced a remarkable EFS rate of 59.7 months. Taken together, these findings demonstrate that neoadjuvant pembrolizumab can produce durable long-term benefit for this high-risk and difficult-to-treat patient population.
“I think this trial does constitute a leap forward and a new standard of care.” – Robert Ferris
Merck advisor Robert Ferris, who talked to us about the impressive trial results. He especially stressed their role in fostering evidence-based treatment practices for HNSCC.
Safety and Adverse Effects
Further complicating provider opinions was the safety profile of pembrolizumab – a concern based on this trial’s findings related to the therapy’s safety. The trial found that immune-mediated adverse events developed in 43.2% of patients treated with the drug. Hypothyroidism was the most common diagnosis, impacting 24.7% of participants.
The trial brought attention to the serious side, with 10% of patients experiencing grade 3 or higher immune-mediated adverse events. This revelation should give us serious pause when considering the value of treatments. Given the seriousness of these deleterious effects, critical questions remain. We need to weigh the phototoxic benefits against the balance of other adverse effects and risk of pembrolizumab therapy.
One death from severe pneumonitis occurred among patients treated with pembrolizumab. This is a reminder that thorough follow-up and treatment of all reactions must remain top priority.
“We have a great deal of new things we need to do.” – Robert Ferris
Future Implications for Treatment Standards
Ravindra Uppaluri received research grants and consulting fees from Merck. He noted his excitement that pembrolizumab had the potential to redefine treatment paradigms for HNSCC. According to him, “This new data warrants an immediate shift in the prevailing standard of care to include neoadjuvant and adjuvant pembrolizumab. For the first time in over two decades, patients suffering from this difficult to treat disease have a new innovative treatment option.”
As more data becomes available, it is crucial for healthcare providers to weigh the benefits of improved response rates against the risks of significant adverse effects. Continued research and clinical inquiry are imperative for incorporating pembrolizumab into established treatment paradigms. Patient safety needs to be at the forefront at every step of this process.
Leave a Reply