Sacituzumab govitecan in HR+HER2- metastatic breast cancer: the randomized phase 3 EVER-132-002 trial

Abstract

Sacituzumab govitecan (SG) significantly improved progression-free survival (PFS) and overall survival (OS) versus chemotherapy in hormone receptor-positive human epidermal growth factor receptor 2-negative (HR⁺HER2^-) metastatic breast cancer (mBC) in the global TROPiCS-02 study. TROPiCS-02 enrolled few Asian patients. Here we report results of SG in Asian patients with HR⁺HER2^- mBC from the EVER-132-002 study. Patients were randomized to SG (n = 166) or chemotherapy (n = 165). The primary endpoint was met: PFS was improved with SG versus chemotherapy (hazard ratio of 0.67, 95% confidence interval 0.52-0.87; P = 0.0028; median 4.3 versus 4.2 months). OS also improved with SG versus chemotherapy (hazard ratio of 0.64, 95% confidence interval 0.47-0.88; P = 0.0061; median 21.0 versus 15.3 months). The most common grade ≥3 treatment-emergent adverse events were neutropenia, leukopenia and anemia. SG demonstrated significant and clinically meaningful improvement in PFS and OS versus chemotherapy, with a manageable safety profile consistent with prior studies. SG represents a promising treatment option for Asian patients with HR⁺HER2^- mBC (ClinicalTrials.gov identifier no. NCT04639986 ).

Fig. 1. CONSORT diagram.

Of 485 patients screened, 154 were not randomized to a treatment group. The remaining 331 patients were randomized to the SG or chemotherapy groups. ^aChemotherapy selected at randomization: eribulin (n = 131), vinorelbine (n = 13), capecitabine (n = 11) or gemcitabine (n = 10). ^bOne patient was randomized to the SG group but was erroneously administered chemotherapy. ^cOther reasons included clinical deterioration, pregnancy or administrative problems. ^dOther reasons included clinical deterioration, pregnancy, administrative problems or patient nonadherence/protocol violations.

Fig. 2. Kaplan–Meier estimates of PFS and OS.

a, Kaplan–Meier curve of PFS per BICR in patients treated with SG (n = 166) versus chemotherapy (n = 165). b, Kaplan–Meier curve of PFS per INV in patients treated with SG versus chemotherapy. c, Kaplan–Meier curve of OS in patients treated with SG versus chemotherapy. The median PFS and OS were calculated using the Kaplan–Meier method. The HR values were estimated using a stratified Cox proportional-hazards model, and the P values were calculated using a stratified log-rank test. Dashed blue and grey lines indicate median values, and dashed black lines indicate landmark time points. ^aStratified log-rank P value. NE, not estimable.

Fig. 3. Subgroup analysis of PFS.

PFS per BICR with SG versus chemotherapy was analyzed across multiple subgroups. The median PFS was calculated using the Kaplan–Meier method, and HR values were estimated using a Cox proportional-hazards model. ^aHER2-low was defined as IHC score of 1+ or score of 2+ with a negative fluorescence in situ hybridization result; HER2 IHC0 was defined as an IHC score of 0.

Extended Data Fig. 1. Subgroup analysis of OS.

OS with SG versus chemotherapy was analyzed across multiple subgroups. Median OS was calculated using the Kaplan–Meier method, and HR values were estimated using a Cox proportional-hazards model. ^aHER2-low was defined as IHC score of 1 + , or score of 2+ with negative fluorescence in situ hybridization result; HER2 IHC0 was defined as IHC score of 0.

Extended Data Fig. 2. EQ-5D-5L questionnaire responses.

Patient responses to the EuroQoL EQ-5D-5L questionnaire were descriptively evaluated for patients randomized to SG (n = 161, 111) or chemotherapy (n = 157, 121) at baseline and end of treatment in the EQ-5D-5L-evaluable population.