Joshua M. Bauml, MD
The FDA approval of pembrolizumab (Keytruda) as a treatment for patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) in August 2016 was extremely significant for this patient population, which previously had limited options following progression on a platinum-based chemotherapy.
The approval was based on the phase Ib KEYNOTE-012 study, which demonstrated that pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17% in patients with recurrent/metastatic HNSCC.
Several other studies are further evaluating the immunotherapy agent in HNSCC. Preliminary results of the phase II KEYNOTE-055 study—which included 92 evaluable patients who received pembrolizumab after failing platinum and cetuximab therapies—were presented at the 2016 ASCO Annual Meeting.
In an interview with OncLive, lead study author Joshua M. Bauml, MD, an assistant professor of Medicine, Hospital of the University of Pennsylvania and the Veteran's Administration Medical Center, discusses the impact of pembrolizumab’s success in HNSCC, the results of the KEYNOTE-055 study, and what he sees on the horizon for the PD-1 inhibitor in this field.
OncLive: What role do you envision pembrolizumab having in this patient population?
Bauml: It is going to play a critical role in head and neck cancer. The other agents that are available have limited efficacy, and are associated with significant toxicities. This is a clear improvement for our patient population with limited options.
What were the key takeaways from KEYNOTE-055?
Patients with recurrent/metastatic head and neck cancer that is refractory to both platinum-based therapy and cetuximab (Erbitux) really have very few options. The historical reference population we usually use is patients treated with methotrexate, which has a response rate of 5% and an overall survival (OS) of only about 6 months. There is a really great need for this. For pembrolizumab, which is an anti–PD-L1 agent, there is biologic rationale to think that it would be active in this patient population. PD-L1 and PD-L2 are unregulated in head and neck cancer.
What KEYNOTE-055 did is really try and create a homogenous patient population. Rather than a large phase I study, here are patients all who have failed both platinum-based therapy and cetuximab. We have really identified the sickest patient population.
What we are able to show in this study was that the drug was well tolerated and it has a response rate of 17% to 18%, which compares favorably for the 5% seen with the prior data with methotrexate. The OS rate was 8 months, which again compares very favorably to the 6 months seen with methotrexate. This was true, even though 85% of patients had received at least 2 prior treatments for head and neck cancer.
What did this study tell us about the safety of pembrolizumab in head and neck cancer?
The rate of grade 3 through 5 treatment-related adverse events was 12% in our study. Nearly all of the side effects are what you would expect with pembrolizumab; those have been reported in multiple other studies. There was 1 treatment-related death due to pneumonitis, which is a rare side effect of this class of drugs.
Outside of that, it was a really well-tolerated agent. The fact that if you compared grade 3 through 5 toxicities of 12% with cytotoxic chemotherapy, this is a very well-tolerated agent.
How common is it for patients to fail both platinum-based therapy and cetuximab?
Any patient who has recurrent or metastatic head and neck cancer is going to go through these agents if they survive long enough to get them. Basically, we know that these are the limited tools in our toolbox. We have platinum, we have cetuximab, and then we are really out of options. Many patients have received cetuximab in the locally advanced setting and so we have already lost one of our active treatments. This affects a lot of people.
What is next for pembrolizumab in head and neck cancer?
There are currently phase III studies evaluating pembrolizumab in head and neck cancer both in combination with and versus traditional cytotoxic chemotherapy to see if we can move up the treatment earlier for patients. The key difference between pembrolizumab and cytotoxics is beyond the improved safety profile. However, we have durable responses; 75% of those patients who responded are still responding to this day. That is really not something that we see.
What are the biggest questions that remain regarding the treatment of patients with metastatic head and neck cancer?
One of the key questions that relates to immunotherapy—and this covers all tumors—is trying to identify who the 20% of patients are that will respond. Eighty percent of our patients are not responding to our therapies.
Identifying a biomarker to enrich this patient population is very critical. Right now, I would not select patients for pembrolizumab by virtue of PD-L1 status because there were responses in the PD-L1–negative cohorts.
Bauml J, Seiwert TY, Pfister DG, et al. Preliminary results from KEYNOTE-055: Pembrolizumab after platinum and cetuximab failure in head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2016;34 (suppl;abstr 6011).