Immune therapy drugs show promise in treating esophageal cancer

Gary Hines didn’t want to lose his hair.

The Harrison resident, diagnosed with esophageal cancer in 2021, worried about looking his best for his son’s wedding.

“I was all worked up,” said Hines, 60, retired after 30 years with the Harrison Township Water Authority. “Turns out, I never lost one hair.”

That was only the start of what Hines considers miracles. He was treated for Stage 3 cancer through a clinical trial by Allegheny Health Network, Baylor Scott & White Health and Johns Hopkins School of Medicine.

Hines’ medical team at AHN tested two courses of neoadjuvant immunotherapy for advanced gastroesophageal cancer — a relatively rare disease affecting about 22,000 patients a year in the United States, but one that is deadlier than other types of cancer.

It is the seventh-leading cause of cancer-related deaths in the country, according to cancer.gov.

The multimillion “phase 1b” trial ran five years, from 2017-22.

It investigated whether immune checkpoint inhibition medications, in combination with standard of care chemoradiotherapy, given before removing a gastroesophageal tumor, would improve outcomes. Immune checkpoints are like a brake on the human immune system, preventing a response from being so strong that it destroys healthy cells.

Findings, published in March in Nature Medicine, showed the experimental treatment can help improve two-year overall survival rates.

“This is often a debilitating disease with limited treatment options, and these new findings give hope for the future,” said Dr. Ali Zaidi, medical director of aerodigestive research at the AHN Cancer Institute and a co-first author of the study.

Zaidi said the five-year survival rate for patients with advanced esophageal cancer is typically less than 20%.

With the experimental doublet immunotherapy drug combination, data show a promising 94% overall survival rate at two years, warranting further investigation in a larger randomized trial, he said.

“The regimens demonstrated good antitumor activity and clinical outcomes in a small data set,” Zaidi said.

Thirty-two patients participated in the 1b trial.

Hines has been recurrence-free for nearly three years.

“The immunotherapy was just a test then. It was an option for me, but I believe it was the game-changer,” Hines said. “I never got sick, just tired. I went to chemo for seven weeks, and I would come home and wash my car, cut the grass and watch the Pirates on TV.

“I’m not saying it was easy. I lost 58 pounds, but the immunotherapy was why I had such a good response.”

Initially, Hines saw his doctor because his sugar skyrocketed to 800. A normal level is about 100.

No sooner did he get that under control when he started having trouble swallowing his food. On a constant diet of Tums, Hines said his heartburn was crippling.

“I had had covid and I thought maybe I had an infection,” Hines said.

A routine endoscopy turned up the startling diagnosis of cancer.

“I was shocked,” he said. “I just thought, ‘Oh, great.’ ”

Dr. Kirsten Newhams was Hines’ surgeon.

She is the associate program director for the Minimally Invasive Foregut and Advanced Endoscopy Fellowship at the Esophageal Institute at AHN.

Newhams said the clinical trial’s significant promise is to move the needle on better long-term outcomes for patients.

“We have the opportunity to profile a patient’s tumor and understand how it is acting,” Newhams said. “Most patients are presenting at an advanced state. We’re looking for opportunities for more precise treatment and to catch people earlier. This is a disease we want to know sooner rather than later and if there are more nuanced ways to treat it.

“This provides for individualized treatment.”

The results of the study give hope to a broader landscape of cancer treatments, said Zaidi, who conceptualized the study with data from his lab.

Research proved that by tracking circulating tumor DNA (ctDNA), physicians can predict early whether patients will have a bad response or good clinical feedback, he said.

Zaidi said researchers monitored the effectiveness of the therapy in real time and at a molecular level by analyzing blood samples to detect ctDNA.

They found that, after the therapy, the amount of tumor DNA in the blood appeared to be undetectable for most patients, suggesting the individual’s immunotherapy treatment had been effective.

If studying the patient’s blood can predict survival outcomes, the tool could potentially be used to treat other types of tumors, they believe.

“We are very excited about the data,” Zaidi said. “It gives great hope to improve outcomes. The question now is, how do we build on the benefit?”

Zaidi is urging better screening and more collaboration among medical experts on underfunded and understudied cancers such as this one.

“We want to leverage what we’ve been doing by making strategic study investments,” he said.

For Hines, who underwent a nine-hour surgery to remove the top of his stomach and bottom two-thirds of his esophagus, the experimental treatment was an answered prayer.

Despite enduring a feeding tube, chemotherapy and radiation, Hines said he’s doing well.

“I help watch my grandson three days a week,” he said. “There is nothing that affects my day to day.”