Sacituzumab Govitecan Produces Consistent Clinical Outcomes in mTNBC, Irrespective of Neutropenia and Diarrhea AEs

Sacituzumab govitecan-hziy (Trodelvy) produced comparable efficacy outcomes for patients with metastatic triple-negative breast cancer (TNBC) who had a higher incidence of grade 2 or 3 diarrhea and neutropenia vs patients in the overall population, according to a post hoc analysis of the phase 3 ASCENT trial (NCT02574455) presented at the 2023 ESMO Breast Cancer Annual Congress.

Data from this analysis showed that using established guidelines to monitor and intervene early for diarrhea and neutropenia may result in longer treatment durations and sustained benefit from sacituzumab govitecan.

Overall, patients treated with sacituzumab govitecan (n = 267) in the ASCENT trial achieved significantly improved efficacy outcomes compared with physicians’ choice chemotherapy; however, 54% of patients experienced grade 3 or higher neutropenia and 32% experienced grade 2 or greater diarrhea.

In a poster, investigators wrote, “Overall survival [OS] for patients who experienced grade 2 or higher diarrhea differed from those who did not experience diarrhea; however, in the time-varying Cox model, no significant difference was observed after adjusting for age, race, and BMI [body mass index]…differences in PFS [progression-free survival] and OS were not observed in the time-varying Cox model after adjustment for age, race, and BMI.”

The median PFS for patients with grade 2 or higher diarrhea (n = 81) was 6.9 months (95% CI, 4.2-8.3) vs 4.9 months (95% CI, 3.7-5.7) for patients who did not have a grade 2 or higher event (n = 173; HR, 0.72; 95% CI, 0.52-0.98; P = .04). The median OS was 14.3 months (95% CI, 11.8-16.7) vs 10.9 months (95% CI, 9.5-13.8), respectively (HR, 0.69; 95% CI, 0.50-0.94; P = .02).

PFS and OS outcomes were similar for patients with or without neutropenia. Patients with neutropenia that was grade 2 or higher (n = 138) experienced a median PFS of 5.6 months (95% CI, 4.0-6.5) compared with 4.9 months (95% CI, 4.1-5.9) for those who did not have a grade 2 or higher event (n = 116; HR, 0.91; 95% CI, 0.68-1.21; P = .51). The median OS was 13.5 months (95% CI, 10.8-14.5) compared with 11.2 months (95% CI, 10.1-14.1), respectively, (HR, 0.99; 95% CI, 0.74-1.32; P = .95).

An examination of the association between PFS, OS, and the onset of grade 3 or higher neutropenia or diarrhea was performed after an adjustment for age, race, and BMI occurred. Adjusted rates included PFS for diarrhea (HR, 0.98; 95% CI, 0.71-1.36; P = .92), PFS for neutropenia (HR, 1.2; 95% CI, 0.89-1.61; P = .24), OS for diarrhea (HR, 0.78; 95% CI, 0.56-1.08; P = 0.14), and OS for neutropenia (HR, 1.06; 95% CI, 0.80-1.42; P = 0.68). Investigators noted that the Cox regression was conducted with a time-varying covariate.

No grade 5 events were observed and there was 1 treatment discontinuation due to a grade 2 diarrhea event which was not attributed to the study drug.

The median duration of treatment with sacituzumab govitecan was 19.1 weeks (range, 0.1-128.6) and relative dose intensity was 99.7% (range, 53.7%-107.1%) for all patients with neutropenia and diarrhea. Treatment duration and relative dose intensity were similar for patients with and without grade 3 or higher neutropenia. However, patients with grade 2 or higher diarrhea experienced a longer duration of treatment (27.1 vs 17.4 weeks) and lower dose intensity than those without diarrhea (97.7% vs 99.8%).

Baseline characteristics were well balanced for those with diarrhea and neutropenia. Most patients were 65 years or older (81%), had visceral metastases at baseline (83%), and had a median baseline BMI of 25.3 kg/m2 (range, 15.0-49.3). The median number of prior systemic regimens was 4 (range, 2-17), and the time from metastases to first sacituzumab govitecan dose was 17.9 months (range, –0.1 to 191.4). Patients were White (82%), Black (10%), Asian (4%), or other (4%).

ASCENT protocol randomly assigned patients to intravenous sacituzumab govitecan given at 10 mg/kg on days 1 and 8 in every 21-day cycle until unacceptable toxicity or progression or treatment of physician’s choice which included capecitabine, eribulin, vinorelbine, or gemcitabine. Stratification occurred based on number of prior therapies received, geographic region, and brain metastases. Further, investigators noted protentional reporting bias may have resulted from the open-label study.

Disclosures: Dr de Azambuja declares consultancy fees from AstraZeneca, Gilead, ImmunoPharma, Libbs, Lily, MSD, Nektar, Novartis, Odonate, Pierre Fabre, Roche/Genetech, SeaGen, Synthon, and Zodiac, and research grants from AstraZeneca, GSK, Novartis, Roche/Genetech, and Servier.

Reference

de Azambuja A, Jacobs F, Lambertini M, et al. Relationship of diarrhea and neutropenia events with outcomes in patients (pts) with metastatic triple-negative breast cancer (mTNBC) treated with sacituzumab govitecan (SG): post hoc analysis from the phase 3 ASCENT study. Presented at: 2023 ESMO Breast Cancer Annual Meeting. May 11-13, 2023; Berlin, Germany.