Retrospective review: No difference in PFS, OS with radiation before PD-1/PD-L1 inhibition


CHICAGO (FRONTLINE MEDICAL NEWS) – Exposure to radiation therapy prior to PD-1/PD-L1 therapy was not associated with improved outcomes in a retrospective review of 66 lung cancer patients.

The patients had stage IIIB or IV non–small cell lung cancer, median age of 64 years, received at least 6 weeks of single-agent anti-PD-1/PD-L1 therapy in the second-line setting or beyond, and had survived at least 8 weeks from immunotherapy initiation. Compared with 13 patients who received no radiation therapy, the 53 who received any prior radiation therapy – including 44 with extracranial radiation and 22 with intracranial radiation – did not differ significantly with respect to progression-free survival (median 4-5 months; hazard ratio, 0.83), or overall survival (median of about 12 months in both groups; HR, 0.96), Christopher Strouse, MD, of the University of Iowa, Iowa City, reported at the Chicago Multidisciplinary Symposium in Thoracic Oncology.

There also were no significant differences in the outcomes between those who had extracranial radiation and those who had intracranial radiation (HRs for PFS and OS, respectively, 0.91 and 1.19), or (on univariate analysis), between those receiving any vs. no intracranial radiation therapy (HRs for PFS and OS, respectively, 0.92 and 0.98), Dr. Strouse said.

The patients who received extracranial radiation therapy had lower lymphocyte counts at the time of anti-PD-1/PD-L1 therapy initiation vs. those who received only radiation therapy (mean lymphocyte count, 809 vs. 1,519), and those who received intracranial radiation therapy were younger than those who did not (median age, 59 vs. 65 years), but the groups were similar with respect to other variables, including gender, histology, performance status, smoking history, KRAS mutation, and number of prior lines of systemic therapies. Anti-PD-1/PD-L1 therapies are promising treatment options for metastatic non–small cell lung cancer, and combining these agents with other immune-modulating therapies may enhance their efficacy and lead to a greater proportion of patients with responses to these treatments, Dr. Strouse noted.

“It’s known that immune response depends on a lot of steps, even beyond the PD-1/PD-L1 axis, and one possible explanation for some of these patients [not responding] may be that there is some failure along the way in some other step,” he said. “Our hypothesis was that radiation therapy would be helpful in overcoming some of these barriers.”

However, in this study, which is limited by small sample size and single-institution retrospective design, no such effect was identified.

The findings conflict with some larger studies, including the recently-reported PACIFIC study, which showed a significant PFS benefit in lung cancer patients who received chemoradiation therapy followed by treatment with the PD-L1 inhibitor durvalumab.

Dr. Strouse said he looks forward to seeing further reports looking into the effects of radiation therapy at different doses and timing.

Invited discussant Heather Wakelee, MD, of Stanford (Calif.) University, also stressed the limitations of the University of Iowa study, and noted that while there are many unanswered questions, findings such as those from the PACIFIC trial show that radiation and PD-L1 inhibition is here to stay.

“It appears safe; there will be more coming,” she said.

Dr. Strouse reported having no disclosures. Dr. Wakelee has been the institutional principal investigator for studies of nivolumab, tocilizumab, and other agents. She has consulted for Peregrine, ACEA, Pfizer, Helsinn, Genentech/Roche, Clovis, and Lilly, and received research/grant support from Clovis, Exelixis, AstraZeneca/Medimmune, Genentech/Roche, BMS, Gilead, Novartis, Xcovery, Pfizer, Celgene, Gilead, Pharmacyclics, and Lilly.


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