Adding radiation after immunotherapy improves PFS for some pts with metastatic NSCLC

September 26, 2019

Adding precisely aimed, escalated doses of radiation after patients no longer respond to immunotherapy reinvigorates the immune system in some patients with metastatic non-small-cell lung cancer (NSCLC), increasing progression-free survival (PFS). Findings of the phase II randomized trial were presented at the 61st Annual Meeting of the American Society for Radiation Oncology (ASTRO).

"This study provides one more important piece of data that indicates that, for some patients, the immune system can be a really powerful tool to combat metastatic lung cancer," said Allison M. Campbell, MD, PhD, a resident in the department of therapeutic radiology at Yale Cancer Center and lead author on the study. "It points us in the direction of places to look for biomarkers that might predict which patients would best respond to this type of therapy."

NSCLC accounts for roughly 80-85% of all lung cancers. Approximately 57% of patients with NSCLC have already progressed to stage IV cancer at the time of diagnosis, meaning that tumors have spread to other parts of the body, making it difficult to cure. This type of cancer may be treated with radiation therapy, immunotherapy, surgery, chemotherapy or targeted drug therapy to relieve symptoms and allow patients to live longer.

This phase II prospective trial explored the benefits of treating one cancerous lesion with stereotactic body radiotherapy (SBRT) in patients with NSCLC whose cancer had continued to spread after treatment with pembrolizumab, a type of immunotherapy. Dr. Campbell and her team looked to see if tumors outside the treated area would also shrink, how long patients lived before their disease progressed after treatment and what was happening to the immune systems of those patients who responded well to the combination of SBRT and immunotherapy.

The study included 56 patients with NSCLC, all of whom had two or more measurable tumors at enrollment. Of these, six patients had already received immunotherapy and were immediately treated with SBRT, which delivers precise, intense doses of radiation. The other 50 patients had not yet been treated with immunotherapy; of these, 16 were treated with SBRT after their disease progressed after treatment with pembrolizumab (also known by its brand name Keytruda).

A total of 21 patients completed both treatments and lived, on average, five months longer without their disease progressing any further. In two patients (9.5%), tumors outside the treated area shrank by 30% or more and stayed that way for more than a year. Ten patients (47.6%) experienced disease stabilization (tumors neither grew nor shrank) following the addition of SBRT.

"We weren't surprised to see that some patients had tumors shrink outside the field of radiation," said Dr. Campbell, who added that the research team really wanted to learn more about what was happening in the immune systems of those patients. "There's been a lot of interest in how radiation can stimulate the immune system. We wanted to learn all we could from our very best responders."

A closer analysis of the peripheral blood cells in patients whose tumors shrank or did not grow suggested that T cells played an important role in the immune system response, said Dr. Campbell. "We found that there were two things that correlated with patients living longer without their disease progressing," she said. "Those two things were T cells infiltrating the tumor before immunotherapy was given, and the presence of immune-related side effects at any time during the course of treatment, such as inflammation of the lung or inflammation of the GI tract. Patients who experienced these side effects lived a longer period of time before the disease progressed."

Dr. Campbell and her team were able to identify two different types of T cells performing important functions in fighting the tumors. In patients who responded well to the combination therapy, they found both CD8 T cells, which can kill cancer cells directly, and CD4 T cells, which help the immune system organize its response to threats such as cancer. "We saw different proportions of these cells in our good responders versus our bad responders," she said, "as well as different activation statuses. In people who responded well to the combination therapy, we saw a population of CD8 T cells that looked more excited, and in those with poor responses, we saw a population of CD4 T cells with inhibitory markers. The bigger picture here is that there are signatures in the peripheral blood that are promising avenues for future identification of people who will respond well to SBRT combined with immunotherapy."

The next step, she said, will be to validate these findings in a larger population.

"We are starting to see that the combination of immunotherapy and radiation is safe and there are some hints that for certain patients, radiation might be an important option when immunotherapy no longer curbs disease progression," said Dr. Campbell. "Our study lays the groundwork for a phase III randomized trial, which is the gold standard for changing guidelines and clinical practice."
-end-
The abstract, "Final results of a phase II prospective trial evaluating the combination of stereotactic body radiotherapy (SBRT) with concurrent pembrolizumab in patients with metastatic non-small cell lung cancer (NSCLC)," was presented in detail at ASTRO's 61st Annual Meeting in Chicago. Audio and slides from the news briefing are available at http://www.astro.org/ASTRO19press. To schedule an interview with Dr. Campbell and/or outside experts, contact ASTRO's media relations team at press@astro.org.

ABOUT ASTRO

The American Society for Radiation Oncology (ASTRO) is the world's largest radiation oncology society , with more than 10,000 members who are physicians, nurses, biologists, physicists, radiation therapists, dosimetrists and other health care professionals who specialize in treating patients with radiation therapies. The Society is dedicated to improving patient care through professional education and training, support for clinical practice and health policy standards, advancement of science and research, and advocacy. ASTRO publishes three medical journals, International Journal of Radiation Oncology * Biology * Physics, Practical Radiation Oncology and Advances in Radiation Oncology; developed and maintains an extensive patient website, RT Answers; and created the nonprofit foundation Radiation Oncology Institute. To learn more about ASTRO, visit http://www.astro.org.

American Society for Radiation Oncology

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.