Novel immunotherapy approach benefits high risk HPV-positive head and neck cancer patients

UChicago researchers show that combination immunotherapy and chemotherapy treatments required less intensive treatment plans for patients with head and neck cancers.

In a new clinical study published in JAMA Oncology, researchers from the University of Chicago Medicine Comprehensive Cancer Center have reported novel therapy with addition of immunotherapy, nivolumab to neoadjuvant chemotherapy, nab-paclitaxel, and carboplatin resulted in tumor shrinkage that led to decreased local treatments in majority of oropharyngeal cancer patients associated with human papillomavirus (HPV).

HPV infection is a major risk factor for oropharyngeal cancer (OPC), which is a type of head and neck cancer that affects the region including the tonsils, base of tongue and back of the tongue. The number of HPV-positive (HPV+) OPC cases are on rise especially in young adults in United States. The most common treatments for this type of cancer are chemotherapy, radiotherapy, or a combination of the two. Although these therapies can be effective, they also cause toxic side effects that can compromise the patients’ ability to swallow, speak and eat.

Neoadjuvant therapy to lower toxicity

The head and neck cancer research team at the University of Chicago had been working for a long time on developing treatment regimens that can significantly lower treatment-related toxicity without compromising treatment effectiveness and tumor control.

In 2019, Everett Vokes, MD, John E. Ultmann Distinguished Service Professor of Medicine, and his team tested a less aggressive combination treatment in order to reduce treatment-related side effects and improve quality of life with excellent cure rates. The trial, named OPTIMA, involved up-front treatment with a regimen of chemotherapy drugs nab-paclitaxel and carboplatin. This strategy, known as neoadjuvant therapy, has resulted better outcomes for many cancer types because shrinking the tumor with chemotherapy and radiation therapy before standard treatment results in smaller tumors and less of a chance the tumor will come back.

What made OPTIMA unique is that instead of standard treatment, Vokes and colleagues followed a “de-escalation” strategy where chemo and radiotherapy doses were reduced based on how the cancer responded to treatment.

The first OPTIMA study produced encouraging results; 90% of patients on the de-escalated regimen reported less toxicity with excellent long-term survival. “This appeared to be a very good treatment strategy to destroy the cancer and improve functional outcomes without debilitating long-term side effects,” said Ari Rosenberg, MD, Assistant Professor of Medicine at University of Chicago Medicine.  

Immunotherapy in HPV+ OPC patients

Recent developments in immunotherapies, such as anti-PD-1 inhibitors, combined with chemotherapy have shown promising results in improving survival rates in repeated and/or metastatic OPC patients; however, immunotherapies have not been tested in the curative setting where the cancer is completely eradicated to bring the patient’s health back to pre-cancer condition.

Following the success of the original OPTIMA trial, Rosenberg and colleagues conducted the OPTIMA II trial to test whether the addition of neoadjuvant immunotherapy, nivolumab to chemotherapy, nab-paclitaxel and carboplatin followed by locoregional treatments would lower toxicity effects and improve cure rates in HPV+ OPC stage III and IVB patients. 

“We hypothesized that adding the PD-1 inhibitor, nivolumab, to the neoadjuvant chemotherapy backbone from the first OPTIMA trial would improve responses, thereby facilitating de-escalation for more patients. The study found that 71% of patients had a deep response, which was the threshold that qualified patients for de-intensification,” said Rosenberg.

The researchers observed improvement in overall progression-free and overall survival in 86% of patients that received de-intensified chemo-radiation. Moreover, de-intensified treatment was associated with benefits such as improved quality of life, fewer feeding tube rates for shorter amounts of time, and smaller drops in weight during and after treatment in these patients.

PD-L1 expression and tumor DNA to select patients

Interestingly, the patients who have PD-1 ligand (PD-L1) expression on their tumors seemed to respond well to neoadjuvant chemoimmunotherapy with deeper responses, as well as trend toward improved survival.

“We also found, which was quite interesting, that using a tumor DNA blood test before treatment and after two or three cycles of chemo immunotherapy, clearance of tumor DNA early in chemo immunotherapy was associated with an improvement in progression-free survival, meaning that this could be a very helpful biomarker to better select patients for de-intensified treatment,” said Rosenberg.

Taken together, this study suggests that PD-L1 expression on tumor samples and circulating tumor DNA in blood can guide in patient selection for immunotherapy-based neoadjuvant therapies.

“This is really the first trial testing immunotherapy in the neoadjuvant chemotherapy setting with the de-escalation strategy. We need to continue to select the right patients for de-escalation along with testing novel therapies and bringing them into the earlier stage setting to not only improve survival and cure rates but also minimize treatment-related toxicity,” said Rosenberg.

This work was supported by Bristol Myers Squibb, Celgene, and the University of Chicago Medicine Comprehensive Cancer Center.

Additional authors include: Nishant Agrawal, Aditya Juloori, John Cursio, Zhen Gooi, Elizabeth Blair, Jeffrey Chin, Daniel Ginat, Olga Pasternak-Wise, Rifat Hasina, Evgeny Izumchenko, Ellen MacCracken, Rachelle Wolk, Nicole Cipriani, Mark Lingen, Alexander Pearson, Daniel Haraf, and Everett Vokes from University of Chicago, Chicago, Illinois; Tanguy Seiwert from Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland; Anna Starus and Frederick Jones from Sysmex-Inostics Inc, Baltimore, Maryland.


Explore the Biological Sciences Division