Dr Llombart-Cussac on the Implications of Prophylaxis for Neutropenia and Diarrhea in Advanced Breast Cancer

Antonio Llombart-Cussac, MD, PhD, medical oncologist, chairman, Medical Oncology Service, University Hospital Arnau de Vilanova, discusses clinical implications from the phase 2 PRIMED trial (NCT05520723) that evaluated prophylactic measures for the prevention of neutropenia and diarrhea related to treatment with sacituzumab govitecan-hziy (Trodelvy) in patients with triple-negative (TNBC) or hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

In PRIMED, patients being treated with sacituzumab govitecan also received granulocyte colony-stimulating factor (G-CSF) and loperamide during the first 2 cycles of treatment, and investigators sought to measure the incidence of grade 3 or higher neutropenia and grade 2 or higher diarrhea during the first 2 cycles.

 showed that after the first two cycles any-grade neutropenia occurred in 28% of patients, and 34% of patients experienced any-grade diarrhea. Grade 3 or higher neutropenia was reported in 16% of patients, meeting the study’s primary end point (

 =.001). Notably, no patients experienced febrile neutropenia. Grade 2 or higher diarrhea was reported in 16.0% of patients (

 = .084); 4% had grade 3 diarrhea, and no patients had grade 4 diarrhea.

Llombart-Cussac explains that the readout of findings from PRIMED have already influenced his clinical practice, where he has adopted of these prophylactic strategies for patients with advanced breast cancer receiving sacituzumab govitecan. From his experience, adding these agents to treatment with the antibody-drug conjugate has shown to be convenient for both patients and clinicians, he adds.

Although the PRIMED trial included a relatively small population of 50 patients, including 32 with TNBC and 18 with HR-positive/HER2-negative breast cancer, studies like this still have the ability to affect clinical practice, Llombart-Cussac emphasizes. By integrating prophylactic measures into standard treatment protocols, the trial offers a path to improve quality of life for patients and allow them to receive increased benefit from treatment, he explains. As the oncology field continues to evolve, the focus on preventing treatment-related adverse effects through proactive measures is likely to gain further traction, he concludes.

Videos

Antonio Llombart-Cussac, MD, PhD, on the implications of prophylaxis for sacituzumab govitecan–related neutropenia and diarrhea in advanced breast cancer.

Antonio Llombart-Cussac, MD, PhD, discusses preventing neutropenia and diarrhea with sacituzumab govitecan in HR+/HER2– advanced breast cancer. 

Antonio Llombart-Cussac, MD, PhD, medical oncologist, chairman, Medical Oncology Service, University Hospital Arnau de Vilanova, discusses preventing neutropenia and diarrhea in patients with triple-negative or hormone receptor (HR)–positive, HER2-negative advanced breast cancer receiving sacituzumab govitecan-hziy (Trodelvy).

The phase 2 PRIMED trial (NCT05520723) focused on the prevention of sacituzumab govitecan–related neutropenia and diarrhea. The study evaluated the efficacy of prophylactic treatments administered after each dose of sacituzumab govitecan, Llombart-Cussac says. The study demonstrated that prophylactic treatment with granulocyte colony-stimulating factor was highly effective in preventing neutropenia. This regimen significantly reduced the incidence of neutropenia, eliminating the need for more complex interventions, Llombart-Cussac reports.

After the first two cycles, the incidence of any-grade neutropenia and diarrhea was 28% and 34%, respectively. Eight patients (16%) experienced grade 3 or higher neutropenia, meeting the primary end point (

 =.001). Additionally, eight patients (16%) had grade 2 or higher diarrhea, with 4% experiencing grade 3 diarrhea, indicating a numerical benefit from prophylactic loperamide (

=.084). Importantly, no patients developed febrile neutropenia, Llombart-Cussac reports. Regarding diarrhea, although the primary end point was not met, the use of loperamide prophylaxis resulted in a notable reduction in diarrhea events. However, this was accompanied by constipation in some patients, an adverse effect (AE) related to loperamide, Llombart-Cussac notes. Llombart-Cussac suggests that although loperamide is effective, alternative strategies may need to be explored to manage diarrhea without causing constipation.

Overall, the PRIMED trial findings indicate that prophylactic interventions can significantly mitigate the risk of neutropenia and diarrhea in patients receiving sacituzumab govitecan. The straightforward administration schedule for neutropenia prevention proved effective and well tolerated, Llombart-Cussac says. The findings for diarrhea underscore the need to balance efficacy with proper AE management.

Dr Llombart-Cussac on Preventing Neutropenia and Diarrhea in HR+/HER2– Advanced Breast Cancer

Antonio Llombart-Cussac, MD, PhD, chairman of the Medical Oncology Service at the University Hospital Arnau de Vilanova in Valencia, Spain, discusses the MERIBEL study, which assessed first-line eribulin (Halaven) for taxane-resistant patients with HER2-negative metastatic breast cancer.

The goal of this study, says Llombart-Cussac, was to investigate a treatment for the metastatic breast cancer patients that have the worst prognosis— those with HER2-negative tumors.

The median overall survival for this patient population is less than 15 months.

Patients in the phase II, multicenter, single arm, trial received eribulin as a single-agent on days 1 and 8 of 21 day cycles until progression or unacceptable toxicity. The drug was extremely well tolerated and there were very few treatment interruptions or stops, according to Llombart-Cussac.

The response rate was 20% and the median time to progression was 4 months with eribulin. While these results may not be very impressive, it is important to consider that other agents have shown 2 months time to progression in this patient population, says Llombart-Cussac. In addition, 3 patients achieved more than 1 year of treatment with eribulin. This means that patients that are sensitive can maintain long periods of response with less side effects than other drugs.

Antonio Llombart-Cussac, MD, PhD, chairman of the Medical Oncology Service at the University Hospital Arnau de Vilanova in Valencia, Spain, discusses the MERIBEL study, which assessed first-line eribulin (Halaven) for taxane-resistant patients with HER2-negative metastatic breast cancer.
 

Dr. Llombart-Cussac on Eribulin in HER2-Negative Metastatic Breast Cancer

Antonio Llombart-Cussac, MD, PhD, medical oncologist, chairman, Medical Oncology Service, University Hospital Arnau de Vilanova in Valencia, Spain, discusses the CASCADE study, which assessed declines in treatment efficacy over time in patients with metastatic breast cancer, during an interview at the 2016 ESMO Congress.

The overall goal of the study was to examine patients with metastatic breast cancer in "real-life" scenarios, as opposed to clinical trial settings, explains Llombart-Cussac. Oncologists believed that the patients in clinical trials were very well-selected and therefore did not represent an accurate population for treatment.

The results of this study strongly support the prioritization of the most active treatment options for the initial lines in order to produce the longest overall survival in patients with metastatic breast cancer.

Antonio Llombart-Cussac, MD, PhD

Articles

Dr Llombart-Cussac on the Implications of Prophylaxis for Neutropenia and Diarrhea in Advanced Breast Cancer

Dr Llombart-Cussac on Preventing Neutropenia and Diarrhea in HR+/HER2– Advanced Breast Cancer

Dr. Llombart-Cussac on Eribulin in HER2-Negative Metastatic Breast Cancer

Dr. Llombart-Cussac on the CASCADE Study in Metastatic Breast Cancer