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David S. Ettinger, MD, FACP, FCCP

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Does Adding Radiotherapy to Immunotherapy Improve Outcomes in Metastatic NSCLC?

By: Vanessa A. Carter, BS
Posted: Monday, April 4, 2022

F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute, Boston, and colleagues evaluated the potential benefit of combining the PD-L1 inhibitor durvalumab plus the CTLA-4 inhibitor tremelimumab with radiotherapy in patients with metastatic non–small cell lung cancer (NSCLC). Although radiotherapy did not seem to increase patient responses, PD-L1 plus CTLA-4 therapy may be a promising treatment option for some patients. These findings were published in The Lancet Oncology.

“Data from our randomized trial suggest that durvalumab/tremelimumab should be further explored for its ability to benefit patients with NSCLC who have progressed on previous [PD-L1–directed] therapy,” the study authors concluded. “Improved patient selection by T-cell–infiltrated tumors or other markers could be a worthy strategy to try to improve response rates and clinical benefit.”

This phase II, open-label trial enrolled 90 patients with metastatic NSCLC who experienced disease progression on previous PD-L1 therapy, of whom 78 were treated. Participants were randomly assigned to receive either durvalumab plus tremelimumab (n = 26) or in combination with low-dose radiotherapy (n = 26) or hypofractionated radiotherapy (n = 26). Study treatment continued until 1 year or disease progression.

The majority (85%) of patients underwent previous chemotherapy before enrollment; 32% received nonimmune therapy. The median duration of response across all groups was 10.3 months, with two responders in the low-dose radiotherapy group and one in the hypofractionated radiotherapy group alive and progression-free at the last follow-up. At the median follow-up of 12.4 months, there appeared to be no difference in overall response rates, overall survival, or progression-free survival between the durvalumab/tremelimumab arm and either radiotherapy arm.

The most common grade 3 or 4 adverse events were hyponatremia and dyspnea. Serious treatment-related adverse events affected one patient given durvalumab/tremelimumab, five given low-dose radiotherapy, and four given hypofractionated radiotherapy. One death was attributed to respiratory failure in the low-dose radiotherapy group and was likely related to study therapy; 39 patients died during study treatment.

Disclosure: For full disclosures of the study authors, visit thelancet.com.


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