EL1SSAR Data Shed Light on Leveraging Atezolizumab Plus Nab-Paclitaxel in PD-L1+ TNBC

PD-L1+ TNBC | Image Credit: ©
Sebastian Kaulitzki – stock.adobe.com

Primary findings from the prospective phase 3b EL1SSAR study (NCT04148911) examining frontline treatment with atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) showed safety and efficacy results that were consistent with findings from the phase 3 IMpassion130 study (NCT02425891) in a more selected population of patients with PD-L1–positive advanced triple-negative breast cancer (TNBC).

Regarding safety, the primary end point of the study, 47% (95% CI, 39%-54%) of patients who received atezolizumab combination (n = 182) experienced grade 3 or higher adverse effects (AEs), and the most common effects included neutropenia, asthenia, paresthesia, decreased neutrophil count, decreased white blood cell count, anemia, leukopenia, increased alanine aminotransferase, peripheral neuropathy, neurotoxicity, increased aspartate aminotransferase, and peripheral edema.

Moreover, 12% (95% CI, 8%-18%) of patients experienced grade 2 or higher immune-mediated AEs. The most frequent grade 2 or higher immune-mediated AEs were hepatitis (lab abnormality; n = 8), hepatitis (diagnosis; n = 4), pneumonitis (n = 3), colitis (n = 2), and rash (n = 2). The median time to first onset for these respective AEs were 52 days (range, 22-433), 144 days (range, 27-287), 109 days (range, 25-472), 313 days (range, 238-387), and 89 days (range, 70-108); the median duration was 35 days (range, 15-92), 64 days (range, 3-124), 14 days, 11 days (range, 4-17), and 74 days (range, 13-135), respectively.

“Safety results were consistent with known safety profiles of study drugs and IMpassion130, with no new safety findings,” Suzette Delaloge, MD, MSc, of the Department of Cancer Medicine at Gustave Roussy, in Villejuif, France, said in a late-breaking presentation of the data. “Progression-free survival [PFS] and overall survival [OS] of the overall EL1SSAR population were consistent with the PD-L1–positive population of IMpassion130.”

Evaluating EL1SSAR: Eligibility, Treatment, End Points, and More

The global, single-arm trial included patients with untreated measurable unresectable locally advanced or metastatic TNBC. Those who had stable asymptomatic central nervous system metastases, an ECOG performance status of 2, or select autoimmune diseases were permitted.

A total of 470 patients were screened, and investigators locally assessed PD-L1 status by leveraging the VENTANA PD-L1 (SP142) assay. A total of 182 patients were identified to have PD-L1–positive TNBC, and 97 patients underwent optional central PD-L1 assessment. Patients received 840 mg of atezolizumab on days 1 and 15 combined with 100 mg/m2 of nab-paclitaxel on days 1, 8, and 15 every 28 days. Treatment continued until disease progression or intolerable toxicity.

In addition to the primary safety end points, key secondary end points included AEs, serious AEs, and OS, as well as investigator-assessed PFS by RECIST 1.1 criteria in all patients and the subgroup of patients with PD-L1 positivity. Exploratory end points included the concordance between local and central PD-L1 assessment, as well as safety and efficacy in prespecified patient subgroups.

Examining Efficacy Data

In all patients (n = 182), the median OS was 27.0 months (95% CI, 22.0-33.8) with the combination, with 12-, 24-, and 36-month OS rates of 74%, 53%, and 41%, respectively. The median PFS was 7.4 months (95% CI, 5.6-10.6), with a 12-month PFS rate of 36%. Notably, 15% of patients experienced a PFS longer than 2 years.

In the centrally confirmed PD-L1–positive subgroup (n = 66), the median OS was not evaluable (NE; 95% CI, 29.4-NE); the 12-month OS rate was 89%, the 24-month OS rate was 71%, and the 36-month OS rate was 55%. The median PFS in this group was 11.1 months (95% CI, 7.4-16.8) with a 12-month PFS rate of 47%.

Additional Safety Takeaways

Patients received a median of 6 cycles each of atezolizumab (range, 1-62) and nab-paclitaxel (range, 1-63). Any AEs were reported in 96% (95% CI, 92%-98%) of patients, and 84% of these cases were noted to be related to treatment. Serious AEs were experienced by 16% of patients (95% CI, 11%-23%), with 6.6% of these effects related to treatment. Moreover, 1.6% of patients experienced a grade 5 AE. AEs of special interest occurred in 62% of patients.

AEs led to drug interruption or dose modification for 59% of patients, 53% of which were atezolizumab interruption. Moreover, 23% of patients experienced AEs that resulted in study drug discontinuation, with 8.8% of these being discontinuation of atezolizumab.

Exploratory Revelations Pertaining to PD-L1 Concordance

Of the 96 samples that were locally assessed as PD-L1 positive, 31 were PD-L1 negative on central testing, translating to a 67% concordance.

“In post hoc analyses, PFS and OS in the centrally tested PD-L1–[negative] subgroup was consistent with the PD-L1[–positive] subgroup,” Delaloge concluded. The median OS was 40.1 months (95% CI, 27.1-NE); 12-, 24-, and 36-month OS rates were 90%, 74%, and 58%, respectively. The median PFS was 11.2 months (95% CI, 8.3-14.6); the 12-month PFS rate was 50%.

Disclosures: Dr Delaloge cited the following financial interests: serving on an advisory and scientific board (institution) for Elsan; an advisory board for Gilead and Novartis; and serving as a steering committee member (institution) for BMS, Roche/Genentech, and Sanofi. Funding was received from Banque des Territoires/France 2030 and the European Commission.

Reference

Delaloge S, Martin M, Ciruelos EM, et al. Primary results from EL1SSAR, a prospective phase 3b study of first-line atezolizumab plus nab-paclitaxel therapy for patients with PD-L1+ advanced triple-negative breast cancer. Presented at: 2025 ESMO Congress; May 14-17, 2025. Abstract LBA3.