Dr. Suzette Delaloge from Gustave Roussy presented primary results from the global, single-arm phase IIIb EL1SSAR trial at the ESMO Breast Cancer Congress 2025, confirming the efficacy and safety of atezolizumab plus nab-paclitaxel in patients with PD-L1-positive advanced triple-negative breast cancer (TNBC).
The study enrolled 182 patients with previously untreated, measurable, unresectable locally advanced or metastatic TNBC who tested positive for PD-L1 expression (≥1% on tumor-infiltrating immune cells using the VENTANA SP142 assay). Building on the IMpassion130 trial, EL1SSAR expanded eligibility criteria to include patients with stable CNS metastases, ECOG performance status 2, and selected autoimmune diseases.
Treatment Regimen and Safety Profile
Patients received atezolizumab (840 mg on days 1 and 15) and nab-paclitaxel (100 mg/m² on days 1, 8, and 15) in 28-day cycles until disease progression or unacceptable toxicity. The median treatment duration was six cycles, with 7% of patients continuing treatment beyond three years.
Safety results aligned with known profiles of both drugs, with no new safety signals identified. Grade ≥3 adverse events occurred in 47% of patients (95% CI, 39%-54%), with the most common being neutropenia, asthenia, and paresthesia. Grade ≥2 immune-mediated adverse events were reported in 12% of patients (95% CI, 8%-18%), primarily hepatitis, pneumonitis, and colitis. No treatment-related deaths occurred.
"Safety results were consistent with known safety profiles of study drugs and IMpassion130, with no new safety findings," Dr. Delaloge stated during her presentation.
Efficacy Outcomes Demonstrate Clinical Benefit
The EL1SSAR trial showed impressive efficacy results, particularly in patients with centrally confirmed PD-L1-positive status. In the overall population (n=182), median progression-free survival (PFS) was 7.4 months (95% CI, 5.6-10.6) and median overall survival (OS) reached 27.0 months (95% CI, 22.0-33.8). The 12-, 24-, and 36-month OS rates were 74%, 53%, and 41%, respectively.
Notably, 15% of patients experienced PFS longer than two years, demonstrating durable responses in a subset of patients.
In the centrally confirmed PD-L1-positive subgroup (n=66), outcomes were even more favorable:
- Median PFS: 11.1 months (95% CI, 7.4-16.8)
- Median OS: Not Estimable (95% CI, 29.4-NE)
- 12-month OS rate: 89%
- 24-month OS rate: 71%
- 36-month OS rate: 55%
Patients without prior anticancer therapy experienced superior survival (median OS: 33.8 months) compared to those previously treated (OS: 22.3 months), supporting early use of this combination in the treatment course.
Importance of Accurate PD-L1 Testing
A critical finding from the EL1SSAR trial was the discordance between local and central PD-L1 testing. Of 96 samples locally assessed as PD-L1-positive, 31 were PD-L1-negative on central testing, resulting in only 67% concordance.
"This underscores the importance of rigorous biomarker assessment in clinical decision-making," Dr. Delaloge emphasized. "Accurate PD-L1 testing is essential to identify patients most likely to benefit from immunotherapy."
Interestingly, in post-hoc analyses, patients with centrally tested PD-L1-negative status still showed favorable outcomes similar to the PD-L1-positive subgroup, with median OS of 40.1 months (95% CI, 27.1-NE) and median PFS of 11.2 months (95% CI, 8.3-14.6).
Clinical Implications
The EL1SSAR trial confirms that atezolizumab plus nab-paclitaxel offers a meaningful therapeutic option for patients with PD-L1-positive advanced TNBC in real-world practice. The expanded eligibility criteria provide valuable data on treatment outcomes in patient populations often excluded from clinical trials.
Dr. Erika Hamilton, Director of Breast Cancer Research Program at Sarah Cannon Research Institute, commented: "Suzette Delaloge presents EL1STAR - broadened population for 1L abraxane and atezo (brain Mets, ECOG2, autoimmune diseases). Safety and efficacy very in line with what we expected. 12% G2 greater immune AEs, in central PDL1+, PFS 11.1 Mo."
These results reaffirm the clinical benefit of atezolizumab in appropriately selected patients with advanced TNBC and may influence future diagnostic workflows and treatment strategies for this aggressive breast cancer subtype.
Study Design and Patient Population
The global, single-arm EL1SSAR trial (NCT04148911) screened 470 patients, with 182 identified as having PD-L1-positive TNBC by local assessment. Of these, 97 patients underwent optional central PD-L1 assessment.
Primary endpoints focused on safety, while secondary endpoints included adverse events, serious adverse events, overall survival, and investigator-assessed progression-free survival by RECIST 1.1 criteria. Exploratory endpoints examined concordance between local and central PD-L1 assessment and evaluated safety and efficacy in prespecified patient subgroups.
The trial's findings are particularly significant for patients with this aggressive breast cancer subtype, for whom effective treatment options have historically been limited. The EL1SSAR results provide further evidence supporting immunotherapy as a valuable component of the treatment arsenal for PD-L1-positive advanced TNBC.
