KEY POINTS
- The multicentre open-label AZTEC trial (NCT03464942) randomized 54 women with advanced triple-negative breast cancer across eight Australian centres; 50 patients were included in the modified intention-to-treat analysis. Participants had an Eastern Cooperative Oncology Group performance status of 0–1 and received treatment in the first- or second-line metastatic setting.
- Patients received stereotactic ablative radiotherapy to one to four metastases using either 20 Gy in one fraction or 24 Gy in three fractions, followed by atezolizumab 1,200 mg every three weeks for up to 24 months. At least one lesion had to remain untreated for systemic response assessment.
- Median progression-free survival was 2.5 months with single-fraction treatment and 3.1 months with three fractions. Neither arm rejected the prespecified null hypothesis of a two-month median progression-free survival, and no preferred radiotherapy schedule was identified.
- Median overall survival was 21 months with 20 Gy in one fraction and 15 months with 24 Gy in three fractions, with a combined median of 17 months. The trial was not designed or powered to establish an overall survival difference between the schedules.
- Among 32 patients with measurable untreated disease, four responded outside the irradiated lesions, giving an objective response rate of 12% (95% CI 4–29%). Across the evaluable population, clinical benefit lasting at least six months occurred in 11 of 49 patients (22%), with no difference between arms.
- All 11 patients with clinical benefit had oligometastatic disease with no more than five metastases. The five patients with complete or partial responses maintained disease control for 44–92 weeks, although this subgroup finding was exploratory and lacked a control arm.
- Baseline PD-L1 status was not associated with treatment outcome. Higher circulating progenitor-exhausted CD8-positive T cells were observed in patients with clinical benefit before radiotherapy (p = 0.045), after radiotherapy (p = 0.026), and during atezolizumab (p = 0.0093), but these biomarkers require independent validation.
- Grade 3 or higher treatment-related adverse events occurred in 19% of patients receiving one fraction and 8% receiving three fractions (p = 0.42). There was one grade 4 event, no grade 5 events, and stereotactic radiotherapy was linked to only one grade 3 event: fatigue.
CLINICAL TAKEAWAY
Adding stereotactic radiotherapy before atezolizumab did not generate a sufficient efficacy signal to support either fractionation schedule in unselected advanced triple-negative breast cancer. The durable responses observed exclusively in patients with oligometastatic disease are hypothesis-generating, but require confirmation against contemporary systemic therapy in a controlled trial.