Phase Ib/II study of nivolumab combined with palliative radiation therapy for bone metastasis in patients with HER2-negative metastatic breast cancer.
Masahiro TakadaMichio YoshimuraTakeshi KotakeKosuke KawaguchiRyuji UozumiMasako KataokaHironori KatoHiroshi YoshibayashiHirofumi SuwaWakako TsujiHiroyasu YamashiroEiji SuzukiMasae ToriiYosuke YamadaTatsuki KataokaHiroshi IshiguroSatoshi MoritaMasakazu ToiPublished in: Scientific reports (2022)
Radiation therapy (RT) can enhance the abscopal effect of immune checkpoint blockade. This phase I/II study investigated the efficacy and safety of nivolumab plus RT in HER2-negative metastatic breast cancer requiring palliative RT for bone metastases. Cohort A included luminal-like disease, and cohort B included both luminal-like and triple-negative disease refractory to standard systemic therapy. Patients received 8 Gy single fraction RT for bone metastasis on day 0. Nivolumab was administered on day 1 for each 14-day cycle. In cohort A, endocrine therapy was administered. The primary endpoint was the objective response rate (ORR) of the unirradiated lesions. Cohorts A and B consisted of 18 and 10 patients, respectively. The ORR was 11% (90% CI 4-29%) in cohort A and 0% in cohort B. Disease control rates were 39% (90% CI 23-58%) and 0%. Median progression-free survival was 4.1 months (95% CI 2.1-6.1 months) and 2.0 months (95% CI 1.2-3.7 months). One patient in cohort B experienced a grade 3 adverse event. Palliative RT combined with nivolumab was safe and showed modest anti-tumor activity in cohort A. Further investigations to enhance the anti-tumor effect of endocrine therapy combined with RT plus immune checkpoint blockade are warranted.Trial registration number and date of registration UMIN: UMIN000026046, February 8, 2017; ClinicalTrials.gov: NCT03430479, February 13, 2018; Date of the first registration: June 22, 2017.
Keyphrases
- metastatic breast cancer
- radiation therapy
- end stage renal disease
- ejection fraction
- newly diagnosed
- palliative care
- chronic kidney disease
- free survival
- clinical trial
- stem cells
- prognostic factors
- squamous cell carcinoma
- peritoneal dialysis
- bone mineral density
- advanced cancer
- radiation induced
- rectal cancer
- single molecule