Combination treatment improves lung cancer outcomes, study finds

A new study found that non-small cell lung cancer (NSCLC) patients treated with a combination of low-dose radiotherapy and immunotherapy had higher progression-free survival than patients who received immunotherapy alone two years after treatment.

Findings from researchers at Weill Cornell Medicine, NewYork-Presbyterian and Columbia University’s Vagelos College of Physicians and Surgeons offer hope to people affected by NSCLC, the most common type of lung cancer in the United States. States, accounting for 81% of all lung cancer diagnoses. .

Chemotherapy is frequently combined with immunotherapy to treat people with lung cancer. However, this study, published in Natural communications on December 19, suggested that “the addition of low-dose radiation could increase the options available to patients, particularly those who cannot tolerate chemotherapy,” according to Dr. Nasser Altorki, chief of the division of thoracic surgery at Weill Cornell Medicine. and NewYork-Presbyterian/Weill Cornell Medical Center and the lead author of the paper.

Zachary Walsh, MD/Ph.D. candidate at Columbia University’s Vagelos College of Physicians and Surgeons, was also co-first author of this study.

Previously, a clinical trial initiated by an investigator at NewYork-Presbyterian/Weill Cornell Medical Center and led by Altorki and colleagues enrolled 60 patients with early-stage NSCLC. The randomized phase 2 trial combined radiation therapy with durvalumab, a checkpoint inhibitor that boosts the immune system. These drugs work by releasing the brakes on the immune system to induce a response against tumor cells, but their effects may be insufficient to completely eliminate the cancer.

“Using a low dose of radiation to boost the immune response, rather than a high dose to destroy the tumor, was new to the trial,” said co-senior author Timothy McGraw, professor of biochemistry. at Weill Cornell Medicine. “From this perspective, I believe that Dr. Altorki’s trial design remains unique.”

Dr. Benjamin Izar, assistant professor of medicine at the Vagelos College of Physicians and Surgeons at Columbia University and a medical oncologist at NewYork-Presybeterian/Columbia University Irving Medical Center, was also co-senior author of the paper.

The first results, published in The Lancet Oncology in 2021, demonstrated that the combination treatment eradicated significantly more tumors than immunotherapy alone. In fact, the combination caused a “major pathological response” – one that killed more than 90% of the cells in the tumors that were surgically removed and analyzed during the study.

But would it also improve patient survival? To find out, the researchers continued to follow the cohort for two additional years.

Results from the extended study indicated that dual therapy reduced the risks of cancer recurrence and prolonged progression-free survival. Six of the people who received immunotherapy alone died of cancer. However, in the “dual therapy arm” of the trial, there was only one cancer death and five deaths not related to cancer recurrence.

The team also discovered that cancer-free survival is accompanied by increased immune activity. People who received immunotherapy plus radiation therapy and had major pathological responses had more activated T cells in their blood than those who did not have major pathological responses.

“The appearance of these activated T cells was associated with the absence of cancer recurrence,” said Altorki, who is also the David B. Skinner Professor, MD of Thoracic Surgery and head of the Investigational Therapeutics Program at the Sandra and Edward Meyer Cancer Center. at Weill Cornell Medicine.

The researchers found that participants who developed a major pathological response harbored tissue-resident T cells in their blood, even before treatment began.

“You wouldn’t normally expect to find these cells circulating,” Altorki said. Their presence suggests that in these individuals, the immune system had already detected the tumor and initiated a response. Examining participants’ T cell repertoire could potentially identify individuals who would benefit from combination therapy.

The researchers plan to follow up on this observation in an upcoming trial to evaluate how radiation therapy compares to chemotherapy as a way to augment immunotherapy.

“We have shown that radiation works,” Altorki said. “But does it work as well or better than chemotherapy? That’s what we want to answer now.”