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Does Stereotactic Body Radiotherapy Enhance the Effect of Immunotherapy for Lung Cancer?

By: Joseph Fanelli
Posted: Tuesday, July 30, 2019

Administering stereotactic body radiotherapy before the use of pembrolizumab in patients with non–small cell lung cancer (NSCLC) appears to be well tolerated and active, but future studies are needed to determine whether the use of radiotherapy is influenced by PD-L1 expression, according to findings presented in JAMA Oncology. Radiotherapy did result in a doubling of overall response rates, but outcomes did not meet the study’s predetermined endpoint for a meaningful clinical benefit, concluded Willemijn S.M.E. Theelen, MD, of the Netherlands Cancer Institute, Amsterdam, and colleagues.

“Positive results were largely influenced by the PD-L1–negative subgroup, which had significantly improved progression-free survival and overall survival,” the authors noted. “Further evaluation in a larger phase [II/III] trial is recommended to confirm the findings and elucidate the processes by which [stereotactic body radiotherapy] may activate noninflamed NSCLC tumors toward an inflamed tumor microenvironment, rendering them receptive to immune checkpoint inhibition.”

This multicenter, randomized clinical trial (ClinicalTrials.gov Identifier NCT02492568) enrolled patients diagnosed with advanced NSCLC (regardless of PD-L1 status). Patients received either 200 mg/kg of pembrolizumab every 3 weeks (76 patients) or that same dose of pembrolizumab following 3 doses of 8 Gy radiotherapy (36 patients).

At 12 weeks, patients in the pembrolizumab-alone group exhibited an overall response rate of 18%, versus 36% in the radiotherapy cohort. Patients who underwent radiotherapy also had improved median progression-free survival (6.6 months) and median overall survival (15.9 months), compared with those in the pembrolizumab-alone group (1.9 months and 7.6 months, respectively). Subgroup analyses revealed that patients with PD-L1–negative tumors seemed to benefit the most from the use of radiotherapy. Additionally, the investigators did not observe an increase in treatment-related toxic effects with radiotherapy plus immunotherapy.

Disclosure: The study authors’ disclosure information may be found at jamanetwork.com.



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