Details

Autor(en) / Beteiligte

• David, SP
• Savas, P
• Neeson, PJ
• Luen, SJ
• Foroudi, F
• Siva, S
• Loi, S

Titel

Abstract P2-09-06: Safety and efficacy of stereotactic body radiotherapy and Pembrolizumab in advanced breast cancer patients with 1 to 5 metastases

Ist Teil von

• Cancer research (Chicago, Ill.), 2019-02, Vol.79 (4_Supplement), p.P2-P2-09-06

Erscheinungsjahr

2019

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• Abstract Background Pre-clinical studies have demonstrated that stereotactic body radiotherapy (SBRT) induces immunogenic cell death and tumor antigen release promoting anti-tumor immunity. We hypothesized that the efficacy of SBRT could be improved with the addition of PD-1 blockade in advanced breast cancer (BC) patients with oligometastatic disease. Methods Advanced BC patients with 1 – 5 metastatic sites of disease received SBRT at a dose of 20Gy in 1 fraction to at least 1 metastasis followed by pembrolizumab 200mg IV (within 5 days of SBRT), once every 3 weeks for a total of 8 cycles. The primary endpoint was safety of the combination. The secondary endpoints were response using RECIST 1.1 and PERCIST 1.0 using 18F-Flurodeoxyglucose (FDG)- positron emission tomography (PET) scans as well as local progression-free survival and distant progression-free survival (d-PFS). Correlatives included deep sequencing of the T cell receptor (TCR) CDR3 regions of archival metastatic tumor material and in peripheral blood as well as evaluation of systemic markers of immune activation. Results 15 patients were enrolled between March 2016 and Nov 2017. The number of patients with 1, 2, 4 and 5 metastases treated with SBRT was 9 (60%), 3 (20%), 2 (13%) and 1 (7%), respectively. There were 3 (20%) TNBC, 2 (13%) HER2+ and 10 (67%) ER+/HER2- (Luminal) BC patients. Five (33%) patients experienced Grade 3 or higher Aes. Immune related Aes were reported in 10 (67%) patients, the most common being rash (n=4), thyroid (n=3) and pneumonitis (n=3) with pembrolizumab delayed in 3 (20%) patients and discontinued in 2 (13%) patients. Nine (60%) patients had a complete response or partial response according to RECIST 1.1 criteria and 13 (86%) patients had a complete metabolic response (CMR) or partial metabolic response (PMR) according to PERCIST 1.0 at the 3-month FDG-PET scan. At time of reporting (median follow-up 15 months; range 9-26 months) no deaths or local progression have been observed. Five patients (33%) progressed distantly at 3, 8, 8, 12 and 18 months: 2 of 3 (66%) TNBC, 2 of 10 (20%) Luminal and 1 of 2 (50%) HER2+. Estimated dPFS at 9 months was 80% (95% CI [62% – 100%]). Three patients have reached the 2-year mark without progression (all Luminal). In a patient who remained progression free at 24 months, TCR profiling showed that TCR sequences in a pre-treatment metastatic tumor biopsy were found in peripheral blood and became elevated after combination treatment, along with the emergence of new TCR sequences not seen in the tumor sample. Markers of increased CD8+ and CD4+ T cell activation using flow cytometry of peripheral blood lymphocytes were observed. This data suggests that the treatment induced peripheral expansion of tumor-specific T cells in this responding patient. Further correlatives are pending. Conclusion The combination of SBRT and 6 months of pembrolizumab in advanced breast cancer patients with 1-5 metastases showed an acceptable toxicity profile and promising clinical benefit especially in Luminal BC patients. Evidence of peripheral anti-tumor T cell responses was observed in a patient who remains progression free at 24 months. The potential synergy between these treatment modalities requires further study. Citation Format: David SP, Savas P, Neeson PJ, Luen SJ, Foroudi F, Siva S, Loi S. Safety and efficacy of stereotactic body radiotherapy and Pembrolizumab in advanced breast cancer patients with 1 to 5 metastases [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-06.