Atezolizumab plus paclitaxel and bevacizumab as first-line treatment of advanced triple-negative breast cancer: the ATRACTIB phase 2 trial

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with poor prognosis. The current first-line treatment for advanced TNBC (aTNBC) is determined by the expression of programmed cell death-ligand 1 (PD-L1). In the ATRACTIB trial-a multicenter, single-arm, phase 2 study-we evaluated the combination of atezolizumab, paclitaxel and bevacizumab as first-line treatment for patients with aTNBC, independently of PD-L1 status. The primary endpoint was investigator-assessed progression-free survival. One hundred female patients were enrolled, with most evaluable tumors being PD-L1-negative (97.6%). The primary endpoint was met, with a median progression-free survival of 11.0 months (95% confidence interval (CI): 9.0-13.4; P < 0.001). The objective response rate was 63.0% (95% CI: 52.8-72.4) and median overall survival was 27.4 months (95% CI: 23.4-37.4). No treatment-related deaths or new safety signals were observed. This combination demonstrated significant antitumor activity as first-line therapy for aTNBC patients and merits further investigation. ClinicalTrials.gov Identifier: NCT04408118 .

Fig. 1. Patient disposition of the ATRACTIB trial at the data cutoff date of 17 April 2024.

a, Toxicity prompted the decision to discontinue treatment in four patients, but treatment discontinuations were documented in the context of disease progression. b, Patients discontinued treatment in the framework of the study, but were offered to continue receiving treatment outside the trial, as per treating physician decision and in accordance with the marketing authorization holders’ policy. c, Three discontinuations due to AEs (vomiting and cough, digestive toxicity, pulmonary thromboembolism and autoimmune-mediated hepatitis) and four discontinuations due to serious AEs (cerebral accident, sepsis, fatigue and thrombocytopenia, and ejection fraction decreased). n, number of patients.

Fig. 2. PFS in the full analysis set.

Kaplan–Meier curve of investigator-assessed PFS in the full analysis set. KM, Kaplan–Meier.

Fig. 3. Tumor response and survival analysis in the full analysis set.

a, Waterfall plot of BOR per RECIST v.1.1. Dotted lines mark the thresholds for partial response (≥30% decrease) and disease progression (≥20% increase). b, OS. Reasons for censoring: reaching the end of the study as per protocol (48%), loss to follow up (7%), patient decision (7%) and investigator decision (1%). ^aPatients with only non-target lesions.^bThree patients discontinued before post baseline assessment, one due to progressive disease and two due to withdrawal of consent.

Extended Data Fig. 1. Forest plot of subgroup analysis for progression-free survival according to baseline characteristics and selected prognostic factors.

HR and associated 95% CI were estimated using Cox proportional-hazards models with Breslow’s method of tie handling. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IHC, immunohistochemistry; OS, overall survival; PD-L1, programmed death-ligand 1; ref, reference subgroup.

Extended Data Fig. 2. Forest plot of subgroup analysis for overall survival according to baseline characteristics and selected prognostic factors.

HR and associated 95% CI were estimated using Cox proportional-hazards models with Breslow’s method of tie handling. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; HR, hazard ratio; IHC, immunohistochemistry; OS, overall survival; PD-L1, programmed death-ligand 1; ref, reference subgroup.

Extended Data Fig. 3. Forest plot of subgroup analysis for objective response rate according to baseline characteristics and selected prognostic factors.

The odd ratios and associated 95% CI for ORR were calculated using logistic regression models. CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; OR, Odds ratio, ORR, objective response rate; PD-L1, programmed death-ligand 1; ref, reference subgroup.