Immunotherapy drug bolsters head and neck cancer treatment
Clinical trial shows promising results for patients with intermediate
risk

Date:
February 28, 2022
Source:
University of Cincinnati
Summary:
A clinical trial has shown that the immunotherapy drug pembrolizumab
increased survival rates for head and neck cancer patients with
intermediate risk.



FULL STORY ==========================================================================
A University of Cincinnati clinical trial that added an immunotherapy
drug to standard of care treatment regimens has shown increased survival
rates for head and neck cancer patients with intermediate risk features.


========================================================================== Trisha Wise-Draper, MD, led the trial and was the lead author on a paper detailing its findings that was recently published in Clinical Cancer
Research, a journal of the American Association for Cancer Research.

Targeting the immune checkpoint Wise-Draper said the trial focused on
adding a drug, pembrolizumab, to patients' typical standard care of
treatments. Pembrolizumab, sold under the brand name Keytruda, is an
antibody used in cancer immunotherapy that treats a variety of cancers, including head and neck. The drug targets a pair of receptors that usually
work to turn off the human immune system when the immune system has
finished a job of fighting off a foreign substance that causes sickness.

"Once the virus or infection is cleared, you have to have a way to turn
your own immune system off, to tell it that the infection is gone and
it's time to calm down," explained Wise-Draper, associate professor
of medicine in the Division of Hematology/Oncology in UC's College of
Medicine, Head and Neck Center of Excellence co-leader, medical director
of the University of Cincinnati Cancer Center Clinical Trials Office
and Lab and a UC Health physician.

Tumor cells have learned to kick the receptors that shut the immune
system system off into overdrive, which blocks immune cells from
recognizing that tumor cells are foreign objects that the body should
attack. Pembrolizumab, however, blocks the interaction and keeps immune
cells working, which in turn leads to the immune cells attacking cancerous cells like they are supposed to.



==========================================================================
The drug has been developed as a treatment for multiple cancers, and Wise- Draper said it has shown early success as a treatment for head and neck
cancers that have spread or returned after initial treatment, with early studies reporting effectiveness for about 20% of patients treated.

"And although we're careful to say cure, it does result in what is called 'durable responses,'" she said, explaining that means patients have a
good response to treatment much longer than expected, sometimes for years, "which was a huge advancement over chemotherapy where they may have only
been effective for say nine to 10 months at most," Wise-Draper said.

The hypothesis With the early data looking promising, the UC clinical
trial was seeking to find if the drug would work as an initial treatment
that would prevent the cancer from recurring. Patients with head and
neck cancer -- that are treated with the standard surgery, radiation
and potentially chemotherapy if risk factors warrant it -- typically
see the cancers return about 30%-50% of the time, Wise-Draper said.

"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," she
said. "So we asked if we could add this immunotherapy, the pembrolizumab,
and decrease that risk of cancer coming back." Wise-Draper said the trial
was also designed to examine why some patients respond to pembrolizumab
while others do not. 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 trial Patients enrolled in the trial were given one dose of the
drug before surgery and were evaluated for risk status and grouped
into intermediate- and high-risk groupings after surgery. A patient is considered high risk if part of the tumor is still left behind after
surgery or is not contained in a lymph node.

All patients continued to receive the appropriate standard of care
(radiation alone for intermediate risk or radiation and chemotherapy
for high risk), with six more doses of pembrolizumab also administered
after surgery.

Wise-Draper said the drug caused tumors to begin to die before surgery
in nearly 50% of patients, a better rate than what was found when the
drug was given for metastatic or recurrent head and neck cancer.

"We could see that a lot of these tumors were dying even after that first
dose of pembrolizumab," Wise-Draper said. "That was pretty exciting,
because that was higher than we expected." Less than 70% of patients
in the intermediate group who were treated with radiation alone after
surgery were typically disease free one year following treatment, but
more than 95% of patients in the trial reported one-year disease-free
survival when treated with both radiation and pembrolizumab.

"We had a huge improvement in that, so we saw that pembrolizumab was
definitely increasing their chance of survival, at least compared to
historical controls," Wise-Draper said.

In the group of patients where the drug began to kill the tumor prior
to surgery, 100% reported one-year disease-free survival.

"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." A reliable predictor for patients that will likely do well on
the treatment will also help determine how treatments can be adjusted for patients who receive surgery, pembrolizumab, chemotherapy and radiation
and do not respond well to the treatment.

"That's really where the research is going now is trying to understand
what are those biomarkers between the responders versus the nonresponders
and how we can develop new and better targeted therapies," Wise-Draper
said. "We have a couple of identified markers that will help us
going forward, but we're still doing a lot of research in that area."
Next steps Harvard University researchers have conducted a study similar
to UC's that showed similar success, and the successful findings of
these trials show that a randomized Phase III clinical trial is worth
pursuing. Pharmaceutical company Merck is in the process of conducting a randomized trial comparing patients who receive pembrolizumab in addition
to their standard of care versus patients who receive the standard of
care only.

"That will be a much larger study that will help show if pembrolizumab
truly benefits these groups," Wise-Draper said of the Merck study.

Research at UC into pembrolizumab as a head and neck cancer treatment
is ongoing, with a next round of research being designed to learn how treatments can be more personalized to each patient. 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.

"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." If the
drug continues to prove safe and effective, Wise-Draper said it will mark
a "huge improvement" compared to the current standard of care that can
still lead to a 50% recurrence rate. There is even a possibility that
patients would not need their treatment plan to include surgery, she said.

"If we have a treatment that is less toxic, maybe we can cut down on
the morbidity of surgery and radiation as well as the chemotherapy," Wise-Draper said.

special promotion Explore the latest scientific research on sleep and
dreams in this free online course from New Scientist -- Sign_up_now_>>> ========================================================================== Story Source: Materials provided by University_of_Cincinnati. Original
written by Tim Tedeschi. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Trisha M. Wise-Draper et al. Phase II Clinical Trial of Neoadjuvant
and
Adjuvant Pembrolizumab in Resectable Local-Regionally Advanced
Head and Neck Squamous Cell Carcinoma. Clinical Cancer Research,
2022 DOI: 10.1158/1078-0432.CCR-21-3351 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220228170834.htm

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