The European Medicines Agency has validated a Marketing Authorization application for sacituzumab govitecan-hziy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who had previously received at least 2 therapies, including at least 1 therapy for locally advanced or metastatic disease.
Merdad Parsey, MD, PhD
The European Medicines Agency has validated a Marketing Authorization application for sacituzumab govitecan-hziy for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer who had previously received at least 2 therapies, including at least 1 therapy for locally advanced or metastatic disease.1
The application is now under accelerated review by the agency based on positive data from the phase 3 ASCENT trial (NCT02574455), where the antibody-drug conjugate (ADC) was found to result in a significant improvement in survival vs physician’s choice of treatment (TPC) in patients with TNBC who did not have brain metastases and had received at least 2 prior treatments for metastatic disease.2
Results indicated the sacituzumab govitecan improved progression-free survival (PFS) vs TPC in this population, at a median of 5.6 months (95% CI, 4.3-6.3) vs 1.7 months (95% CI, 1.5-2.6), respectively (HR, 0.41; 95% CI, 0.32-0.52; P <.0001).
“Metastatic TNBC is an aggressive and life-threatening cancer. Unfortunately, for many people with this cancer, there are not enough effective treatment options, and their prognosis is extremely poor,” Merdad Parsey, MD, PhD, chief medical officer at Gilead Sciences, stated in a press release. “The validation of our European Union marketing application is an important step toward addressing the significant unmet medical need for people with metastatic TNBC.”
The phase 3 trial enrolled a total of 529 patients with metastatic TNBC who had received 2 or more chemotherapies for advanced disease. Patients were randomized 1:1 to either intravenous sacituzumab govitecan at 10 mg/kg on days 1 and 8, every 21-day cycle (n = 267) or TPC (n = 262). Patients continued treatment until either disease progression or intolerable toxicity.
The primary end point of the trial was PFS, while secondary end points included PFS for the full population, overall survival (OS), objective response rate (ORR), duration of response (DOR), time to response (TTR), and safety. Notably, the trial was stopped early because of compelling evidence of efficacy per a unanimous recommendation from the Data Safety Monitoring Committee.
The median age of participants was 53.5 years and 99.5% were female; the majority of patients were White and had an ECOG performance status of 1. Moreover, 55.5% were BRCA1/2 negative, 7.5% were positive, and 38% had unknown status. The majority of patients had TNBC at initial diagnosis. Across the arms, patients received a median of 4 prior anticancer regimens, with all patients having received a taxane. Additionally, 7.5% received a prior PARP inhibitor and 27.5% previously received checkpoint inhibitors.
Additional results presented during the 2020 ESMO Virtual Congress showed that the median OS was 12.1 months (95% CI, 10.7-14.0) with sacituzumab govitecan vs 6.7 months (95% CI, 5.8-7.7) with TPC (HR, 0.48; 95% CI, 0.38-0.59; P <.0001).
The ORR achieved with the ADC was 35% vs 5% with TPC (P <.0001). Among those who responded to treatment with the ADC, the complete response rate was 4%, while the partial response rate was 31%; in the control arm, these rates were 1% and 4%, respectively. The median DOR with sacituzumab govitecan was 6.3 months (95% CI, 5.5-9.0) vs 3.6 months (95% CI, 2.8–not evaluable) with TPC (P = .057). Additionally, the clinical benefit rates in the investigative and control arms were 45% and 9%, respectively (P <.0001).
With regard to safety, key grade 3 or higher treatment-related adverse effects (TRAEs) in the investigative and control arms included neutropenia (51% vs 33%, respectively), diarrhea (10% vs less than 1%), leukopenia (10% vs 5%), anemia (8% vs 5%), and febrile neutropenia (6% vs 2%).
Granuloctye colony-stimulating factor was given to 49% of those in the ADC arm vs 23% in the TPC arm. Twenty-two percent of patients in the investigative arm required dose reductions vs 26% of those in the control arm.
Notably, no severe cardiovascular toxicity was reported. Neuropathy greater than grade 2 or interstitial lung disease greater than grade 3 were not reported with sacituzumab govitecan. No treatment-related deaths were reported in the investigative arm vs 1 treatment-related death in the control arm; this patient had neutropenic sepsis.
In April 2020, the FDA granted an accelerated approval to sacituzumab govitecan for the treatment of adult patients with metastatic TNBC who have received at least 2 prior therapies for metastatic disease. The decision was based on data from a phase 1/2 trial in which the ADC elicited an ORR of 33.3% (95% CI, 24.6%-43.1%) per local assessment, with a median DOR of 7.7 months (95% CI, 4.6-11.3).3 Continued approval for the indication is dependent upon verification of benefit in confirmatory trials.
The ADC is also under regulatory review for this indication in the United Kingdom, Canada, Switzerland, Australia, and Singapore. The FDA is also reviewing the agent for potential use in adult patients with locally advanced or metastatic urothelial cancer who have previously received a platinum-based chemotherapy in the neoadjuvant or adjuvant, locally advanced or metastatic setting, and either a PD-1 or PD-L1 inhibitor.