On June 23, 2023, Gilead Sciences announced that Trodvy® (sacituzumab govitecan) received a positive opinion from the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) as a monotherapy for adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine therapy and at least two additional systemic therapies in advanced stages.
Trodelvy clinical treatment data
At the 2023 ASCO Annual Meeting, researchers shared updated safety and efficacy data from the trial. The primary analysis showed that Trodelvy significantly improved PFS (HR, 0.66; 95% CI, 0.53–0.83; P = .0003), prolonged OS (HR, 0.79; 95% CI, 0.65–0.96; P = .020), and median DOR (8.1 months vs. 5.6 months), and induced an ORR higher than the TPC (odds ratio [OR], 1.63; 95% CI, 1.03–2.56; P = .035).
In the hormone receptor-positive, HER2-negative breast cancer patient population, antibody-drug conjugates (ADC; n = 272) showed improved overall survival compared to physician-selective single-agent chemotherapy (TPC; n = 271). At a median follow-up of 12.75 months, the median OS was 14.5 months (95% CI, 13.0–16.0) in the ADC group and 11.2 months (95% CI, 10.2–12.6) in the chemotherapy group (HR, 0.79; 95% CI, 0.65–0.95; P = 0.0133). Trodelvy also improved progression-free survival (PFS) compared to TPC, with median values of 5.5 months (95% CI, 4.2–6.9) and 4.0 months (95% CI, 3.0–4.4), respectively (HR, 0.65; 95% CI, 0.53–0.81; P = 0.0001). The 1-year progression-free survival (PFS) rates in the survey group and the control group were 21% and 7%, respectively.
Other data showed a consistent PFS advantage over TPC observed in all predefined subgroups. The 12-month OS rate for ADC was 60.9% (95% CI, 54.8%–66.4%), compared to 47.1% (95% CI, 41.0%–53.0%) for TPC; at 18 months, these rates were 39.2% (95% CI, 33.4%–45.0%) and 31.7% (95% CI, 26.2%–37.4%), respectively. The 24-month OS rates for the survey and control groups were 25.7% (95% CI, 20.5%–31.2%) and 21.1% (95% CI, 16.3%–26.3%), respectively. Notably, the OS advantage of ADC over TPC was also consistently observed in key predefined patient subgroups.
When assessing PFS by HER2 IHC status, Trodelvy consistently improved PFS but not TPC in patients with HER2 low disease (IHC 1+, IHC 2+/ISH-; unstratified HR, 0.60; 95% CI, 0.44–0.82) and HER2 IHC0 disease (HR, 0.70; 95% CI, 0.51–0.98). The same was true for OS; the unstratified HR for OS was 0.75 (95% CI, 0.57–0.97) for patients with HER2 low disease and 0.85 (95% CI, 0.61–1.14) for patients with HER2 IHC0 disease.
With prolonged follow-up, the ADC-induced ORR was 21%, while the TPC was 14% (OR, 1.66; 95% CI, 1.06%–2.61%; P = 0.027). Among patients responding to sacituzumab, the complete response rate was 1%, the partial response rate was 21%, and the disease stability rate was 52%; 21% of patients had progressive disease, and 6% were unmeasurable for response. The CBR in the study group and control group were 34% and 22%, respectively (OR, 1.80; 95% CI, 1.23%–2.63%; P = 0.0025). The median DOR was 8.1 months (95% CI, 6.7–8.9) and 5.6 months (95% CI, 3.8–7.9), respectively.
Overall, the toxicity profile of the ADC was consistent with previous reports. No new safety signals were observed over the extended follow-up period. The most common treatment-emergent toxicities of severity grade 3 or higher with trodelvy were neutropenia (52%), diarrhea (10%), and fatigue (6%). In the TPC group, the most common grade 3 or higher effects were neutropenia (39%), thrombocytopenia (4%), fatigue (4%), and sensory disturbances (4%).
This positive opinion from CHMP confirms the clinical benefit and value of Trodelvy for pretreated hormone receptor-positive/HER2-negative metastatic breast cancer and represents a positive step toward providing this treatment option to patients.
