Source: UC Health

A clinical trial led by Trisha Wide-Draper, M.D., at the University of Cincinnati (UC) that added permbrolizumab to standard of care treatments for head and neck cancer patients has exhibited increased survival rates with intermediate risk features. The findings were reported late last week in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Pembrolizumab—sold under the brand name Keytruda —is a monoclonal antibody immune checkpoint inhibitor used in cancer immunotherapy that treats a variety of cancers. It works by targeting a pair of receptors that regulate immune response, preventing cancer cells from turning off the immune response to the disease.

As it has for other forms of cancer, pembrolizumab has shown evidence that it may be an effective treatment for some patients with head and neck cancer that has spread after first-line treatments. Early studies have shown it to be effective for roughly 20% of the head and neck cancer patients treated. Wise-Draper noted that many of these patients get a durable response to the treatment, meaning that they will stay cancer-free significantly longer than those who receive chemotherapy, often for years. “[This is] a huge advancement over chemotherapy where they may have only been effective for say nine to 10 months at most,” she said.

Building on some of these early studies, the UC-centered trial sought to develop evidence that pembrolizumab could also be effective as an initial treatment with an eye toward reducing the rate of head and neck cancer recurrence, which occurs between 30% and 50% of the time.

“So instead of waiting for them to come back, could we try to prevent them from coming back? If the cancer came back, they were much harder to cure the second time and had a lot of failure in that group,” Wise-Draper said in a press release. “So we asked if we could add this immunotherapy, the pembrolizumab, and decrease that risk of cancer coming back.”

A secondary goal of the trial was to determine why some patients respond to pembrolizumab while it is ineffective in others. To accomplish this goal, tissue and blood samples were collected before and after administering the drug to analyze factors that contributed to patients responding to the treatment.

The 92 patients enrolled in the trial had resectable squamous cell carcinoma of the oral cavity, larynx, hypopharynx, or orophar- ynx (p16-negative) and clinical stage T3-T4 and/or two or more nodal metastases or clinical extracapsular nodal extension (ENE). Prior to their surgery, patients received a one- to three-week neoadjuvant course of 200 mg of pembrolizumab.

Patients were then stratified by absence (intermediate-risk) or presence (high-risk) of positive margins and/or ENE. All received adjuvant radiotherapy (60–66 Gy) and concurrent pembrolizumab (every 3 weeks  6 doses). Patients with high-risk HNSCC also received weekly, concurrent cisplatin (40 mg/m2).

A surprising result of the trial, Wise-Draper told Inside Precision Medicine was the “high pathological response rate just after 1 dose of treatment and the survival benefit associated.”  In fact, in more than 50% of the patients, the drug caused the tumor to die before surgical resection—a much higher response than had been shown in previous studies of recurrent or metastatic head and neck cancer. Within this group, 100% of the patients were disease-free at one year.

“It was a really strong predictor of patients who are going to do well on this treatment,” Wise-Draper said. “Hopefully that is going to help us design trials to better understand who is going to respond and who is not.”

Other results were also encouraging. While fewer than 70% of patients who receive the current standard of care radiation after therapy were disease-free after one year, 95% of those patients who received standard of care plus pembrolizumab were cancer-free at that time.

Meantime, the search for reliable biomarkers as predictors of response continues. Wise-Draper said that both PD-L1 and Indoleamine 2,3-dioxygenase (IDO) were two biomarkers identified that indicated high response rates to the drug.

Next steps at UC are to continue to study how to provide more personalized treatments to patients with head and neck cancer. According to a UC press release: “Tumor characteristics and biomarkers that can help predict whether a patient will respond to a certain treatment can be analyzed before surgery, with more specific treatment plans hopefully leading to better results.”

Meantime, Merck—the developer of pembrolizumab—is in the process of conducting a randomized clinical trial to compare patients who receive the drug compared to those who receive standard of care treatment only. Further, the UC results, along with a similar study conducted by Harvard University researchers suggest that a Phase III trial is worth pursuing.

“It’s been extremely exciting to see patients do well on this study and seeing their survival increase knowing what the historical rates were, as well as just being able to have a successful study in general is pretty exciting,” Wise-Draper said. “A lot of these developments I didn’t expect to happen so quickly in my career, so it’s really been an exciting process for all of us. Hopefully there’s more to come.”

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