Health-related quality of life with sacituzumab govitecan in HR+/HER2- metastatic breast cancer in the phase III TROPiCS-02 trial

Abstract

Background: The TROPiCS-02 study (NCT03901339) demonstrated that sacituzumab govitecan (SG) has superior clinical outcomes over treatment of physician's choice (TPC) chemotherapy in patients with hormone receptor-positive, human epidermal growth factor 2 receptor-negative (HR+/HER2-) metastatic breast cancer (mBC). Here, we present health-related quality of life (HRQoL) patient-reported outcome (PRO) findings from this study.

Patients and methods: Eligible adults with HR+/HER2- mBC who previously received a taxane, endocrine-based therapy, a CDK4/6 inhibitor, and 2-4 lines of chemotherapy were randomized 1:1 to receive SG or TPC until progression or unacceptable toxicity. PROs were assessed at baseline and on day 1 of each cycle, using the European Organization for Research and Treatment of Cancer Quality-of-Life Core 30 (EORTC QLQ-C30), EQ-5D-5L, and PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE).

Results: Compared to TPC, overall least square mean change from baseline was significantly better for SG for physical functioning and dyspnea, but worse for diarrhea. Time to first clinically meaningful worsening or death was significantly longer for SG in global health status/quality of life, physical functioning, fatigue, emotional functioning, dyspnea, insomnia, and financial difficulties of the EORTC QLQ-C30 and the EQ-VAS, but longer for TPC in diarrhea. Few patients in both arms reported experiencing any worsening to level 3 or 4 treatment-related symptomatic events during treatment, as assessed by 16 PRO-CTCAE items, except for diarrhea frequency and amount of hair loss, which favored TPC.

Conclusions: SG was associated with an HRQoL benefit in most symptoms and functioning, compared with TPC. This supports the favorable profile of SG as a treatment option for patients with pretreated HR+/HER2- mBC.

Keywords: EORTC QLQ-C30; HR+/HER2−; Sacituzumab govitecan; antibody–drug conjugate; metastatic breast cancer; phase III; quality of life.

Figure 1.

Proportion of patients experiencing clinically meaningful change from baseline on the primary PRO domains. Data show the proportions of patients in the PRO-evaluable population (N = 446, with 236 and 210 in the SG and TPC arms, respectively), who experienced clinically meaningful worsening or improvement on the primary domains (ie, reaching/exceeding the responder definition [RD] threshold of −10 or + 10 points for a global health/functioning domain or+10 or −10 points for a symptom domain). Data are shown to the visit where the number of evaluable patients was at least 25 in both arms (indicated by denominators of the fractions under the bars at cycle 11 day 1 [C11D1]). Odds ratios (95% CIs and P-values) between proportions of patients worsening/improving in the SG arm vs TPC arm by visit were calculated using logistic regression; values at visits where the SG arm was significantly different from the TPC arm are shown on each graph. Abbreviations: GHS/QoL, global health status/quality of life; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.

Figure 2.

Observed changes from baseline in PRO scores for primary domains. Data show mean changes from baseline in the SG and TPC arms for the primary domains of interest (from the EORTC QLQ-C30), up to the visit where both arms had at least 25 evaluable patients (cycle 11 day 1 [C11D1]). The middle dotted line indicates the baseline level. Dotted lines labeled “improvement” and “deterioration” indicate the clinically important difference (CID) within an arm for the corresponding change in PRO score to be considered clinically meaningful. Note that an increase of 10 points from baseline indicates a meaningful improvement for global health-related and functional domains, whereas the same change indicates a meaningful worsening for symptom domains. Error bars indicate the 95% CI. Abbreviations: EOT, end of treatment; GHS/QoL, global health status/quality of life; SG, sacituzumab govitecan; TPC, treatment of physician’s choice.

Figure 3.

Proportion of patients with any worsening of level 3 or more during treatment. Data show proportions of patients in the safety population (excluding patients with a score of 3 or 4 at baseline), who showed worsening from baseline to a level of 3 or worse on 9 potentially relevant symptoms (decreased appetite, nausea, vomiting, constipation, abdominal pain, shortness of breath, fatigue, diarrhea, and hair loss) during treatment, as assessed by 16 items selected from the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), an instrument developed to identify cancer treatment-related adverse events. Numbers within bars indicate the percentage of patients showing any worsening of level 3 or greater during treatment. Abbreviations: SG, sacituzumab govitecan; TPC, treatment of physician’s choice.