Adding radiotherapy (RT) to treatment with durvalumab and tremelimumab did not improve outcomes in patients with metastatic non-small cell lung cancer (NSCLC) resistant to anti-PD-1/L1 therapy, according to research published in The Lancet Oncology.
The phase 2 trial is the first randomized study designed to evaluate the addition of RT to PD-1/L1 plus CTLA-4 blockade that also includes a non-radiation control group, according to researchers.
The trial (ClinicalTrials.gov Identifier: NCT02888743) enrolled 90 patients with metastatic NSCLC who had progressed on a PD-1/L1 inhibitor. The patients were randomly assigned to receive durvalumab-tremelimumab only, the drug combination plus low-dose RT, or the drug combination plus hypofractionated RT. Treatment was continued for 1 year or until disease progression.
Patient characteristics were well balanced across the treatment arms. The median age was 65 years in all 3 arms. Most patients were men, non-Hispanic White, had adenocarcinoma, and had received prior RT. Across all arms, patients had received a median of 3 prior lines of therapy.
Ultimately, 78 patients were treated on study. At the interim analysis, the trial was stopped due to futility. The median follow-up was 12.4 months.
There was no significant difference in overall response rates between the no-RT arm, the low-dose RT arm, and the hypofractionated RT arm — 11.5%, 7.7%, and 11.5%, respectively. The median duration of response was 4.9 months in the low-dose RT arm and was not reached in the other arms.
There were no significant differences in progression-free survival (PFS) or overall survival (OS) across the arms. The median PFS was 3.3 months in the no-RT arm, 4.6 months in the low-dose RT arm, and 4.0 months in the hypofractionated RT arm. The median OS was not reached, 9.1 months, and 9.7 months, respectively.
Adverse events (AEs) considered at least possibly related to treatment occurred in 73% of patients in the no-RT arm, 77% in the low-dose RT arm, and 77% in the hypofractionated RT arm.
The most common grade 3 or higher AEs (in the no RT, low-dose RT, and hypofractionated RT arms, respectively) were dyspnea (8%, 12%, and 12%) hyponatremia (4%, 8%, and 12%), and gamma-glutamyl transferase increase (0%, 4%, and 12%).
One patient in the low-dose RT arm died from respiratory failure, which was considered potentially related to study treatment.
“Although we did not show benefit associated with the addition of radiotherapy to immune checkpoint blockade, we cannot exclude the possibility that radiotherapy administered in another tumor type, with different immunotherapy drugs, with different timings relative to immune checkpoint blockade, or using alternative radiotherapy doses or fractionation, would be beneficial,” the researchers concluded.
Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Schoenfeld JD, Giobbi-Hurder A, Ranasinghe S, et al. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: An open-label, multicentre, randomized, phase 2 trial. Lancet Oncol. Published online January 13, 2022. doi:10.1016/S1470-2045(21)00658-6
This article originally appeared on Cancer Therapy Advisor