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CHICAGO -- The addition of stereotactic body radiotherapy (SBRT) to the treatment protocol in patients with metastatic non-small cell lung cancer (NSCLC), whose disease has progressed on immunotherapy, achieved a response in nearly 10% of those patients, a researcher reported here.

Adding SBRT to pembrolizumab (Keytruda) also achieved a disease control rate of 57%, and resulted in a mean of 5 months before further disease progression, reported Allison M. Campbell, MD, PhD, of the Yale New Haven Hospital in Connecticut, in a presentation at the American Society for Radiation Oncology annual meeting.

"We know that we need more therapies for patients with metastatic lung cancer, and we also know that immunotherapy activates the immune system to attack cancer," Campbell pointed out, adding that in some cases adding high doses of radiation to immunotherapy results in a "therapeutic synergy," whereby some tumors that aren't targeted by radiation shrink -- a response called the "abscopal effect."

"We wanted to look for this [abscopal effect] in our trial," said Campbell. "Our question was: Can we add a high dose of radiation given in just a few fractions to a single site of disease to reinvigorate an immune response in patients who progress on immunotherapy?"

This phase II prospective trial included 56 patients with NSCLC whose cancer continued to progress after treatment with pembrolizumab. All patients had at least two measurable tumors at the time they were enrolled in the trial.

Fifty of the patients were immunotherapy-naïve and began pembrolizumab when the trial started. Of these 50, 16 experienced disease progression and were treated with SBRT. The remaining six patients had progressed on anti-PD-1 therapy at the time of enrollment in the trial and were immediately treated with SBRT.

Of the 22 patients treated with SBRT, 21 completed treatment. Campbell and colleagues reported that two patients (9.52%) achieved a partial response (tumors outside the treated area shrank by >30%, which was sustained for more than 1 year), while 10 patients (47.62%) achieved stable disease, for a combined disease control rate of 57.14%.

The researchers also found that patients with elevated tumor infiltrating lymphocytes scores (2 or 3 on a 0-3 scale) showed improved progression-free survival compared with patients that had lower TIL scores (0-1), with a mean of 215 versus 59 days, respectively, while patients with an immune-related adverse event, such as inflammation of the lung or colon, survived longer than patients with no immune-related adverse event (a mean of 208 vs 88 days).

"We also looked at T cells in the peripheral blood ... and found two things that were particularly interesting," reported Campbell. "We found an increased population of CD8+ effector memory T cells in the peripheral blood in patients that had a partial response that lasted a year or more -- and these are the kinds of cells that can kill tumors. We also saw that in patients that had a poor response to radiation, more CD4+ regulatory T cells, and these cells inhibit immune responses."

Benjamin Movsas, MD, of the Henry Ford Cancer Institute in Detroit, commented that this interaction between radiation and immunotherapy raises certain questions, such as how to best combine them, and exploit them.

The fact that 50% of patients in this study had disease that remained stable "suggests that perhaps radiation may be able to reinvigorate the immune system," said Movsas, who was not involved in the study, "Maybe we can get more mileage with immunotherapy out of this approach," he noted.

The study by Campbell's group also demonstrated that in this era of precision medicine, "the immune profile really matters," Movsas added. "Having more CD8 killer T cells actually corresponds to response. This could help the radiation oncologist, over time, better determine who are the patients that will really benefit from these novel, and exciting, strategies."

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