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KEYNOTE-012 Investigator Explains Promise of Pembrolizumab in HNSCC

Laura Panjwani
Published: Tuesday, Jun 28, 2016

Ranee Mehra, MD

Ranee Mehra, MD

Given the lack of treatment options for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), the need for novel therapies is dire, says Ranee Mehra, MD, chief of Head and Neck Oncology at Fox Chase Cancer Center.

“There is activity seen with both pembrolizumab [Keytruda] and nivolumab [Opdivo] in this disease and this is significant—especially in a disease that lacks a lot of standard therapies,” says Mehra. “It is very exciting.”

Mehra was the lead investigator on the KEYNOTE-012 trial, which explored pembrolizumab in patients with recurrent/metastatic HNSCC.

The results were promising, says Mehra. Patients who received treatment with pembrolizumab had an overall response rate (ORR) of 18% and a stable disease rate of 17%.

In patients with HPV-positive disease, the ORR was 24%, and in those with HPV-negative disease, the response rate was 16%. There were 4 complete responses (CR) in each of the HPV groups. In patients treated with a prior platinum-based agent, the ORR was 17% (95% CI, 12-23), with a CR rate of 5%. Patients who were treated with prior cetuximab (Erbitux) and platinum therapy demonstrated an ORR of 15% (95% CI, 9-23) and a CR rate of 5%.

In an interview with OncLive, Mehra discusses what the KEYNOTE-012 findings could mean for patients, the growing role for the immunotherapy agent in head and neck cancer, and what else is on the horizon for the treatment landscape.

OncLive: What were the most significant findings from this study?

Mehra: KEYNOTE-012 was an expansion of a phase Ib trial of pembrolizumab in squamous cell carcinoma of the head and neck. Patients were enrolled in 2 cohorts. We presented the data at the 2016 ASCO Annual Meeting of the combined analysis of 192 patients, including HPV-positive and HPV-negative patients. Our results show responses in both of those subtypes of head and neck cancer, as well as progression-free survival (PFS) and overall survival (OS) data from the single-arm study.

The PFS for the combined analysis was 2 months; the OS was 8 months. What is notable is that there were some patients who had CRs and some patients did complete the 24-month treatment period; therefore, the duration of response in a subset of patients was actually quite impressive.

What should oncologists take away from these findings?

These data give us a longer experience with this agent. As we learn more about the role of immunotherapy in head and neck cancer, it is useful to see not just the response rate, but also the duration of activity that is potentially possible in a subset of patients.

Are there any safety challenges that oncologists should be aware of with pembrolizumab?

The toxicity profile is certainly very different from cytotoxic therapy. While most patients tolerate it very well, oncologists need to be aware of the potential for immune-related toxicities. While it is rare, serious toxicities could include colitis or pneumonitis; we are also seeing endocrinopathies with these patients with thyroid dysfunction. It will require oncologists to be aware of a different type of toxicity profile.

What immunotherapy combinations do you see potential for?

There have been combinations of PD-1/PD-L1 inhibitors with CTLA-4 inhibitors, and those trials are ongoing.

Another class of agents that is being looked at in combination with PD-1 inhibitors is IDO inhibitors. Certainly, there are a lot of other emerging combinations that are in phase I studies right now and are still being explored.

Where are we right now, in terms of biomarker development?

In KEYNOTE-012 and other trials that have been done, we have been looking at PD-1 and PD-L1 expression. From KEYNOTE-012, there are also data regarding the NanoString interferon signature.




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Online CME Activities
TitleExpiration DateCME Credits
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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