Novel Approaches to Head and Neck Cancer at Vanderbilt Ingram Cancer Center

Despite curative intent, there is significant local disease recurrence for patients with head and neck cancers, which highlights a need for better treatment options, explained Jennifer Choe, MD, PhD, assistant professor of medicine, head and neck medical oncology, clinical trials lead, division of hematology and oncology, Vanderbilt University Medical Center (VUMC) at an Institute for Value-Based Medicine^®.

At the event, co-hosted by The American Journal of Managed Care and Vanderbilt-Ingram Cancer Center at VUMC, a group of experts highlighted the way multidisciplinary teams manage head and neck cancer, as well as the latest advances in treatment.

Jennifer Choe, MD

Choe, a medical oncologist led off the session on head and neck cancers with a discussion of novel approaches and radiation. She started with a patient case of a 46-year-old male who had 2 treatment options: laryngectomy plus a bilateral neck dissection or chemoradiation either with or without induction chemotherapy. Since the patient was a teacher and needed to be able to talk, his treatment team went for the second option because it would preserve his larynx.

“But I think we can probably do better than this,” Choe said. “I mean, our goal is to improve upon chemoradiation so that we're going beyond standard of care and improving outcomes for these patients.”

There are ongoing efforts to see how standard of care can be improved upon, for instance through the use of immunotherapy to enhance chemoradiation therapy. Unfortunately, 2 randomized phase 3 trials of chemoradiation in combination with PD-1/PD-L1 inhibitors failed to meet the primary end points.

JAVELIN Head and Neck 100,¹ which evaluated chemoradiation vs chemoradiation plus avelumab and 1-year maintenance avelumab, failed to meet the progression-free survival end point. KEYNOTE-412,² which evaluated chemoradiation vs chemoradiation plus pembrolizumab and 1-year maintenance pembrolizumab, failed to meet its event-free survival end point.

Despite disappointing results with these, they helped to inform additional trials. There was conjecture that the concurrent nature of the treatment might have impacted the outcomes. Radiation causes local immune suppression, which is causing lower responses with immunotherapy in head and neck cancers, Choe explained.

One trial (NCT04892875) set to begin at VUMC will compare chemoradiation with adjuvant PD-1 inhibition and adenosine receptor inhibition in 3 cohorts. “…we’re building out the clinical trial portfolio to try to best serve our head and neck cancer population patients,” she said.

Sarah Rohde, MD, MMHC

Following Choe, Sarah Rohde, MD, MMHC, associate professor, Department of Otolaryngology–Head and Neck Surgery Division, director of Head and Neck Oncologic Surgery, VUMC, discussed promising results treating advanced squamous cell carcinoma.

Sun exposure is very common for the people of Tennessee, which results in advanced skin cancer. When these cancers occur in the head and neck, treatment becomes more complex. However, for years, treatment was the same: surgery with resection and free tissue reconstruction. But now there are more exciting options to offer, Rohde said.

A study³ of 79 patients who received neoadjuvant cemiplimab followed by curative intent surgery found 63% of patients had a complete or partial response and the surgery did not need to be as disfiguring as when it is done without a drug like cemiplimab.

“Responses to cemiplimab is so promising and especially for our head and neck cancer patients,” Rohde said. “But we still don't know the correlation to progression-free survival and overall [survival], and that's what future studies will help us with.”

Eben Rosenthal, MD

Precision is crucial in surgery, especially in sensitive areas like the head and neck, but being precise is challenging when the surgeon cannot actually see the cancer during the procedure. This makes it difficult to determine margins, said Eben Rosenthal, MD, Guy M. Maness Professor and Chair, Department of Otolaryngology–Head and Neck Surgery, professor of Pathology, Microbiology and Immunology, VUMC.

If not enough is removed, the cancer will return, and the patient will have a poor outcome. However, surgeons don’t want to remove more than necessary. He explained that Vanderbilt is conducting trials on an optical dye labeled to the antibody therapy panitumumab, which binds to EGFR, with the goal of allowing the surgeon to actually see the cancer.

The dye can be used during the surgery to provide a better sense of the margin or once the tumor is removed to get a better view of what the specimen looks like.

“I think this is really kind of the future of what surgery will look like in multiple disease types,” Rosenthal said.

Once that specimen is out, a pathology report is created, but it can be very difficult to interpret. Also, the specimen gets destroyed as part of the analysis, which can be challenging weeks later during discussions.

Michael Topf, MD, assistant professor of Otolaryngology–Head and Neck Surgery, VUMC, has been working on creating a working 3D map of specimen that can be annotated and marked up. He says the use of these can lead to more meaningful conversations. He envisions a time when pathology reports are no longer written text but instead are screenshots of these annotated 3D specimen maps identifying the different margins.

Michael Topf, MD

The technology can also have cost implications since surgeons will no longer have to take specimens to the lab, taking time away from a patient under general anesthesia. This technique will have the potential to reduce or eliminate that time a patient is under anesthesia, which can save a hospital money.

“We need to show a way to demonstrate that this [3D scanning] shows value,” Topf said. “[But] I think we all agree this is an improvement upon the current standard of care.”

References

1. Lee NY, Ferris RL, Psyrri A, et al.Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3

2. Merck provides update on phase 3 KEYNOTE-412 trial in unresected locally advanced head and neck squamous cell carcinoma. News release. Merck. July 20, 2022. Accessed September 19, 2023. https://bit.ly/3B1f2yN

3. Gross ND, Miller DM, Khushalani NI, et al. Neoadjuvant cemiplimab for stage II to IV cutaneous squamous-cell carcinoma. N Engl J Med. 2022;387(17):1557-1568. doi:10.1056/NEJMoa2209813