TROPiCS-02: Sacituzumab govitecan offers HRQoL benefits in HR+/HER2- mBC

According to patient-reported outcomes (PROs) from the TROPiCS-02 study, sacituzumab govitecan (SG) vs treatment of physician’s choice (TPC) chemotherapy is associated with health-related quality of life (HRQoL) benefits across most symptoms and functioning domains among patients with hormone receptor–positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC).

SG is an antibody-drug conjugate (ADC) designed to deliver its payload specifically to cancer cells, which should improve efficacy and reduce toxicities compared with those seen with nontargeted therapies. SG’s efficacy and safety in HR+/HER2- mBC after endocrine therapy and ≥2 lines of additional systemic therapy were evaluated in the phase III, open-label TROPiCS-02 study, the results of which led to this ADC’s approval in Europe, US, and Hong Kong, among other regions. [J Clin Oncol 2022;40:3365-3376; Lancet 2023;402:1423-1433]

At interim analysis, PROs were evaluable in 236 patients in the SG arm and 210 patients in the TPC arm. Baseline characteristics were well balanced between treatment arms.[Oncologist 2024;29:768-779.

The TPC arm generally had higher proportions of patients with a clinically meaningful worsening than the SG arm, while the SG arm generally had higher proportions of patients with a clinically meaningful improvement than the TPC arm at the individual level in the primary domains of global health status (GHS)/QoL, physical functioning, role functioning, and fatigue at most assessments up to day 1 of treatment cycle 11. “However, the odds ratio for meaningful improvement in the pain domain did not favour the SG or TPC arm at any visit,” noted the researchers.

For the secondary domains, among patients with clinically meaningful worsening, a greater proportion reported worsening in social functioning and insomnia domains in the TPC arm, while the SG arm had a higher proportion of patients with clinically meaningful worsening in the diarrhoea domain. At the same time, among patients reporting clinically meaningful improvement, the proportion with improvements in insomnia, appetite loss, and diarrhoea was higher in the TPC arm, while the SG arm had a greater proportion of patients with clinically meaningful improvements in emotional functioning and dyspnoea.

The percentages of patients experiencing worsening of PRO–Common Terminology Criteria for Adverse Events items to level 3 or worse during treatment were higher in the SG arm than in the TPC arm for diarrhoea frequency and amount of hair loss. “These exceptions are unsurprising, as both items are part of the adverse event profile of SG. Diarrhoea can be effectively managed according to established guidelines,” commented the researchers.

Time to first clinically meaningful worsening or death was significantly longer in the SG arm for GHS/QoL (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61–0.92; p=0.006), physical functioning (HR, 0.79; 95 percent CI, 0.64–0.97; p=0.022), and fatigue (HR, 0.73; 95 percent CI, 0.60–0.89; p=0.002) domains. Time to first clinically meaningful worsening or death in the secondary domains of emotional functioning and dyspnoea was also significantly longer in the SG arm.

“In conjunction with the previously published efficacy results, the observed HRQoL benefits strengthen the risk-benefit profile of SG over TPC as treatment for HR+/HER2- mBC,” concluded the researchers.