Radiation+immunotherapy can slow tumor growth for some patients with metastatic NSCLC

September 24, 2017

SAN DIEGO, September 24, 2017 - A new study involving patients with stage IV cancer finds that treatment with radiation therapy and immunotherapy can halt the growth of tumors by stimulating the body's immune system to attack the cancer. In the phase II trial, patients with end-stage cancer that had spread to the lungs or liver demonstrated a favorable response to the combined treatment. Between 30 and 60 percent of the patients, depending on the treatment arm, found that their cancer stopped spreading. Findings will be presented today at the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO).

"This combination of immunotherapy and radiation therapy was safe and well-tolerated by patients with late-stage cancers. We were surprised that a large percentage of patients achieved stable disease several months after treatment--meaning that while their tumors didn't shrink, they did stop growing," said James Welsh, MD, lead author of the study and an associate professor of radiation oncology at The University of Texas MD Anderson Cancer Center in Houston.

"It appears that the radiation helped turn the tumor into a vaccine to stimulate an immune response. This heightened immune response was able to keep the tumors stable. Longer follow-up is needed to determine if this benefit of stable disease will endure over time."

One hundred patients were enrolled in a phase II trial examining a combination of high-dose radiation therapy plus immunotherapy for patients with various types of stage IV cancers. Eligible patients included those with metastatic disease that was resistant to standard therapies, with one or more lesions in the liver or lung that was/were amenable to stereotactic radiation and one or more additional metastases not touching the lung or liver lesion. The majority of patients (55%) had adenocarcinomas, while 13 percent had squamous cell carcinomas and the remaining 32 percent had various other histologies.

All patients received four cycles of ipilimumab (3 mg/kg every three weeks) and stereotactic body radiation therapy (SBRT) to the site(s) of metastasis in either the liver or the lungs. Radiation therapy was given either concurrently with or sequentially to immunotherapy. Concurrent radiation began on day two of the first immunotherapy cycle, to a total dose of 50 Gray (Gy) delivered in four fractions. Sequential radiation was given one week after the second immunotherapy cycle to a total radiation dose of 50 Gy delivered in four fractions, or 60 Gy in 10 fractions for larger lung or liver metastases--typically, those larger than four centimeters. Patients were enrolled in a nonrandomized fashion into one of the five treatment cohorts: concurrent lung, sequential 50-Gy lung, concurrent liver, sequential 50-Gy liver, and sequential 60-Gy liver or lung. There were 20 patients in each treatment arm.

Stable disease was achieved for half of the patients in the sequential 50-Gy lung cohort, 45 percent of the concurrent-lung group, 35 percent of the concurrent liver group and 30 percent of the sequential 50-Gy liver group. Sixty percent of patients in the larger-lesion, higher-dose radiation group demonstrated a favorable response to treatment.

The median progression-free survival (PFS) for all patients following radiation therapy combined with immunotherapy was five months (95% CI = 2.7-7.2 months). Median overall survival (OS) was 12 months (95% CI = 9.3-14.6 months). Patients who received sequential radiation to lung metastases rather than to liver metastases had better PFS (p = 0.055, 95% CI = 3.7-6.4) and OS (p = 0.059, CI = 7.9-20.0). No differences were found between the concurrent lung or liver groups for progression-free (p = 0.2) or overall (p = 0.3) survival.

There were no complete responses to treatment, but a partial response was found for three patients who received SBRT concurrently with ipilimumab, including two patients (10%) on the concurrent lung arm and one patient (5%) on the concurrent liver arm. No patients in the sequential radiation groups experienced a partial response.

"A small percentage of patients experienced a potential abscopal effect, where tumors that were not irradiated became smaller after we treated different sites with radiation," explained Dr. Welsh. "For example, one patient with anaplastic thyroid cancer--one of the deadliest types of cancer--experienced a reduction in the primary tumor after we irradiated a lung metastasis. This patient had controlled disease for more than 13 months."

Lesions from non-small cell lung cancer (NSCLC) were most responsive to the combined treatment; two thirds of these patients had a favorable response (partial response or stable disease) following SBRT plus immunotherapy. Response to treatment was scored using immune-related criteria (irRC). Partial response represented a 50 percent or greater decrease in tumor size. Progressive disease represented a 25 percent increase in tumor size. Stable disease responses included those that did not fall into complete, partial or progressive response categories.

No patients experienced Grade 4 or 5 treatment-related side effects. Twenty-seven patients experienced Grade 3 toxicities related to immunotherapy, including colitis (8 patients), diarrhea (7 patients), rash (4 patients), elevation of liver enzymes (3 patients), hypophysitis (3 patients), elevation of bilirubin (1 patient) and intestinal obstruction (1 patient). Two patients experienced Grade 3 toxicities related to combination therapy, including one patient with an increase in liver enzymes and one patient with pneumonitis. Side effects were evaluated using the Common Terminology Criteria for Adverse Events, version 4.0.

"We found that the addition of SBRT for patients who are on immunotherapy to be safe and well-tolerated, meaning that radiation oncologists can feel confident continuing immunotherapy for most patients when adding SBRT to lung or liver metastases. In fact, there may be additional benefit from combining the therapies in terms of improved disease control. Follow-up research in larger clinical trials is needed to determine which types of tumors and patients will respond best to this immunotherapy-radiation approach," said Dr. Welsh.
-end-
The abstract, "Phase II 5-arm trial of ipilimumab plus lung or liver stereotactic radiation for patients with advanced malignancies," will be presented in detail during a news briefing and the clinical trials session at ASTRO's 59th Annual Meeting in San Diego (full details below). To schedule an interview with Dr. Welsh and/or outside experts in immunotherapy and lung cancer, contact ASTRO's media relations team on-site at the San Diego Convention Center September 24 through 27, by phone at 703-286-1600 or by email at press@astro.org.

ATTRIBUTION TO THE AMERICAN SOCIETY OF RADIATION ONCOLOGY (ASTRO) ANNUAL MEETING REQUESTED IN ALL COVERAGE.

This news release contains additional and/or updated information from the study author(s). Full original abstract and author disclosures available from press@astro.org or at http://www.astro.org/annualmeeting.

Study Presentation DetailsAdditional Information on Radiation Therapy and ImmunotherapyResources on Lung Cancer and Radiation TherapyABOUT ASTRO'S ANNUAL MEETING

ASTRO's 59th Annual Meeting, the world's largest scientific meeting in radiation oncology, will be held September 24-27, 2017, at the San Diego Convention Center. The 2017 Annual Meeting is expected to attract more than 11,000 attendees from across the globe, including oncologists from all disciplines and members of the entire radiation oncology team. More than 2,800 abstracts sharing results from clinical trials and other research studies will be presented in conjunction with educational sessions and keynote addresses that underscore the meeting's theme, "The Healing Art and Science of Radiation Oncology." Led by ASTRO President Brian Kavanagh, MD, MPH, FASTRO, the 2017 meeting will feature keynote addresses from Richard D. Zane, MD, FAAEM, Chief Innovation Officer for the University of Colorado Health System; Lucy Kalanithi, MD, FACP, widow of Paul Kalanithi, MD, the best-selling author of "When Breath Becomes Air," with Heather Wakelee, MD, Paul's oncologist; and Vinay K. Prasad, MD, MPH, an assistant professor of medicine at the Oregon Health & Science University. During the four-day meeting, more than 200 exhibitors will demonstrate cutting-edge technology and medical device innovations for radiation oncology. Visit us online for more information about ASTRO's 59th Annual Meeting or press opportunities at the meeting.

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 Radiation Oncology Institute, a nonprofit foundation to support research and education efforts around the world that enhance and confirm the critical role of radiation therapy in improving cancer treatment. To learn more about ASTRO, visit http://www.astro.org and follow us on our blog, Facebook and Twitter.

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.