AZTEC Trial Finds SABR Schedules Do Not Meet PFS Benchmark With Atezolizumab in Advanced TNBC

A randomized phase 2 trial found similar outcomes with single-fraction (SF) and multi-fraction (MF) stereotactic ablative body radiotherapy (SABR) administered before atezolizumab (Tecentriq; Genentech) in women with advanced triple-negative breast cancer (TNBC). Although the combination appeared safe, neither schedule met the study’s prespecified progression-free survival (PFS) benchmark, according to findings published in Nature Communications.¹

Rationale for Combining SABR and Immunotherapy

TNBC lacks estrogen receptor, progesterone receptor, and HER2 targets and is generally more aggressive and difficult to treat than other breast cancer subtypes. In current US practice, pembrolizumab (Keytruda; Merck) plus chemotherapy is an immunotherapy option for unresectable locally advanced or metastatic TNBC with a PD-L1 combined positive score of at least 10.² Atezolizumab’s accelerated US approval with nab-paclitaxel for PD-L1–positive advanced TNBC was withdrawn in 2021 and is no longer FDA-approved for that indication.³

The AZTEC trial (NCT03464942) investigators evaluated a chemotherapy-free strategy based on preclinical evidence showing that focused, high-dose radiation may release tumor antigens and modify the tumor microenvironment, potentially strengthening systemic activity from immune checkpoint blockade. However, the radiation schedule most likely to promote this effect remains uncertain.¹

Two Fractionation Strategies Produce Similar PFS

The multicenter, open-label AZTEC trial enrolled 54 women receiving first- or second-line treatment for advanced TNBC, without selection by PD-L1 status. Participants were randomly assigned to SF SABR at 20 Gy (n = 27) or MF SABR at 24 Gy delivered in 3 fractions (n = 27). Investigators treated 1 to 4 disease sites while leaving at least 1 metastasis unirradiated for response assessment. Atezolizumab 1200 mg every 21 days began within 5 days after SABR and continued for up to 24 months until progression or unacceptable toxicity.⁴

The primary end point was PFS. Median PFS was 2.5 months (90% CI, 1.7-4.5) with SF treatment and 3.1 months (90% CI, 1.8-3.9) with MF treatment. Neither arm rejected the null hypothesis of 2-month PFS, and efficacy was similar across the schedules.¹

Clinical Benefit Concentrated in Oligometastatic Disease

Clinical benefit—complete or partial response, or stable disease lasting at least 24 weeks—occurred in 5 patients (20%) in the SF arm and 6 (25%) in the MF arm. Notably, all 11 patients who derived clinical benefit had oligometastatic disease, and benefit was observed irrespective of PD-L1 expression. Adverse events were comparable between arms, supporting the feasibility of either fractionation approach before atezolizumab.¹

An exploratory peripheral-blood analysis also identified a possible biomarker signal. Higher levels of progenitor-exhausted CD8-positive T cells, known as CD8 TPEX cells, before and during treatment correlated with longer response duration. The association requires prospective validation but could inform development of biomarkers for selecting patients for radiation-immunotherapy combinations.¹

Implications for Oncology Pharmacy Practice

The results do not establish SABR plus atezolizumab as a standard treatment for advanced TNBC or favor SF over MF delivery. The small sample, absence of an atezolizumab-alone control, and short median PFS limit efficacy conclusions. Still, the durable benefit observed exclusively among patients with oligometastatic disease provides a rationale for further trials in a more selected population.

For oncology pharmacists, future research should clarify patient selection, sequencing, and immune-related toxicity monitoring. Pharmacists may also help coordinate SABR and immunotherapy timing, document previous checkpoint-inhibitor exposure, counsel patients about delayed immune-mediated adverse events, and distinguish potential treatment toxicities from radiation-related effects.

REFERENCES

1. David S, Savas P, Siva S, et al. Single-fraction or multi-fraction stereotactic ablative body radiotherapy followed by atezolizumab in advanced triple-negative breast cancer: a randomized phase II trial. Nat Commun. Published online July 27, 2026. doi:10.1038/s41467-026-75660-y

2. Winstead E. Pembrolizumab improves survival in advanced triple-negative breast cancer. National Cancer Institute. Published August 9, 2022. Accessed July 30, 2026. https://www.cancer.gov/news-events/cancer-currents-blog/2022/pembrolizumab-triple-negative-breast-cancer-improves-survival

3. FDA. Withdrawn cancer accelerated approvals. Accessed July 30, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-cancer-accelerated-approvals

4. ClinicalTrials.gov. Stereotactic radiation and immunotherapy in patients with advanced triple-negative breast cancer (AZTEC). NCT03464942. Updated July29, 2023. Accessed July 30, 2026. https://clinicaltrials.gov/study/NCT03464942