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A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) Abstract: BACKGROUND: In patients with advanced triple negative breast cancer (TNBC), immunotherapy has shown acceptable safety and efficacy in a PD-L1 (programmed death-ligand 1) positive population. Pre-clinical evidence has demonstrated that SABR can prime a more effective systemic anti-tumor response in combination with checkpoint inhibition. It is currently unknown if single or multi-fraction SABR scheduling synergises best with atezolizumab therapy. METHODS: This was a multi-centre, open label, phase 2 randomised trial of patients with advanced TNBC, unselected for (PD-L1) status, who had recurred at least 6 months post completion of (neo) adjuvant chemotherapy and received less than 2 lines of treatment in the metastatic setting. Participants were randomised to 20Gy SABR in 1 fraction or 24Gy SABR in 3 fractions to 1-4 sites of disease, with at least one metastasis left unirradiated. Within 5 days following the final fraction of radiotherapy atezolizumab was commenced at a dose of 1200 mg every 21 days and continued for up to 24 months, or until progression or intolerable toxicity. The primary endpoint is progression- free survival (PFS). Secondary endpoints include efficacy according to PD-L1 IHC status (positive: SP142 ≥1%) and TIL (tumour infiltrating lymphocyte) quantity, response assessment, overall survival and safety. Results presented are from interim analysis performed 18 weeks after the last patient commenced treatment. RESULTS: Fifty evaluable patients were recruited and randomised between 20th November 2018 and 12thApril 2021 with a median age of 57 [35 - 79] yrs. Thirty (60%) and 20 (40%) patients had received none or one previous line of chemotherapy in the metastatic setting, respectively. 14/40 (35%) patients were PD-L1 positive at baseline and 26/42 (62%) had TIL≥5%. Median follow-up was 17 months. The median PFS for the 20 Gy arm was 2.5 (90% CI: 1.7-4.5) months, 3.1 (90% CI: 1.8-3.9) months for the 24 Gy arm. For both arms combined, the PFS was 3.1 (90% CI: 1.8-3.9) months, with no difference between the arms, HR 1.2 (95% CI: 0.6-2.1), p=0.64. PFS by PD-L1 IHC status and TIL CONCLUSIONS: The efficacy between single and multi-fraction SABR in combination with Atezolizumab was similar and toxicity was acceptable. Efficacy was seen in PD-L1 positive and negative patients. Longer follow-up is required to assess the effect on OS.. (Research support and funding provided by the imCORE Network on behalf of F. Hoffmann-La Roche; AZTEC ClinicalTrials.gov Identifier: NCT03464942) Table 1.Response AssessmentResponse, n (%)All patients (n = 50)Patients with measurable disease (n = 32)Best objective response (non-SABR lesion)CR3 (6)2 (6)PR2 (4)2(6)NCR/NPD8 (16)0SD13 (26)13 (41)PD24 (48)15 (47)ORR (CR + PR)5 (10); 95% CI: 3-224 (12%); 95% CI: 4-29DCR (CR + PR + SD + non-CR/non-PD ≥24 weeks)a11 (22%); 95% CI: 12-377 (23%); 95% CI: 10-41aOne patient withdrew at 8 weeks and was not assessable for DCR. Citation Format: Steven David, Peter Savas, Shankar Siva, Michelle White, Michael W Neeson, Shane White, Gavin Marx, Robyn Cheuk, Michelle Grogan, Maria Farrell, Jessica Foudoulis, Annette Dempsey, Paul J Neeson, Mathias Bressel, Sherene Loi. A randomised phase II trial of single fraction or multi-fraction SABR (stereotactic ablative body radiotherapy) with atezolizumab in patients with advanced triple negative breast cancer (AZTEC trial) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD10-02.