Radiation plus Immunotherapy May Benefit Some Patients with Metastatic NSCLC

Data presented at the ASTRO annual meeting demonstrate a benefit of radiation plus immunotherapy for patients with advanced disease, including stage IV NSCLC.

It may be possible to repurpose radiation and turn it into a therapeutic cancer vaccine to stimulate an immune response, according to researchers at The University of Texas M.D. Anderson Cancer Center. At the 59th Annual Meeting of the American Society for Radiation Oncology (ASTRO), they reported that adding ipilimumab to stereotactic body radiation therapy (SBRT) may significantly benefit patients with stage IV cancer.

Researchers conducted a phase II trial involving patients with end-stage cancer that had metastasized to the lungs or liver and found that 30% to 60% of the patients appeared to benefit from this combination therapy. “Adding radiation to immunotherapy may help improve the response rate to tumors that did not get irradiation. Currently, only a minority of patients benefit from immunotherapy and by adding in radiation therapy we might be able to expand the benefit to more patients,” said lead study author James Welsh, MD, an associate professor of radiation oncology at The University of Texas M.D. Anderson Cancer Center, Houston, Texas.

The study included 100 patients with metastatic disease that was resistant to standard therapies. The majority of patients (55%) had adenocarcinomas, 13% had squamous cell carcinomas, and 32% had various other histologies. All patients received four cycles of ipilimumab (3 mg/kg every 3 weeks) and SBRT to the sites 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 2 of the first immunotherapy cycle, to a total dose of 50 Gy delivered in four fractions. Sequential radiation was given 1 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.

There were five treatment arms (concurrent lung, sequential 50-Gy lung, concurrent liver, sequential 50-Gy liver, and sequential 60-Gy liver or lung) with 20 patients in each arm. Stable disease was achieved for 50% of the patients in the sequential 50-Gy lung cohort, 45% of the concurrent lung group, 35% of the concurrent liver group, and 30% of the sequential 50-Gy liver group. The study also showed that 60% 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 5 months (range, 2.7-7.2 months). Median overall survival was 12 months (range, 9.3-14.6 months). Patients who received sequential radiation to lung metastases rather than to liver metastases had better PFS. “In our trial, when we added SBRT to the lung or liver, it appeared to be safe when combined with immunotherapy and may further improve response rate of the tumors not directly treated with radiation therapy,” Dr. Welsh told OncoTherapy Network.

Lesions from non-small cell lung cancer were most responsive to the combined treatment and two-thirds of these patients had a partial response or stable disease following SBRT plus immunotherapy.  No patients experienced grade 4 or 5 treatment-related side effects.