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Advanced Breast Cancer Patients Benefit From Targeted, Conventional Therapy Combo, ESMO Studies Show

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NEW YORK – Two breast cancer studies presented at the European Society for Medical Oncology's Virtual Congress on Saturday showed that the addition of targeted therapies to conventional cancer treatments led to higher progression-free and overall survival in hormone receptor (HR) -positive, HER2-negative advanced breast cancer patients.

In one presentation, Sarah Cannon Research Institute's Erika Hamilton shared the final overall survival analysis from the nextMONARCH trial, which looked at the efficacy of abemaciclib (Eli Lilly's Verzenio) either as a monotherapy or in combination with tamoxifen in patients with HR-positive, HER2-negative, metastatic breast cancer.

Abemaciclib, which is a CDK4/6 inhibitor, has been shown to improve progression-free survival when given in combination with endocrine therapy in patients with HR-positive, HER2-negative, metastatic breast cancer. In the Phase III MONARCH2 study, which was presented at ESMO's annual meeting in Barcelona in 2019, the addition of abemaciclib to fulvestrant therapy led to higher overall survival and progression-free survival in this setting.

In the Phase II nextMONARCH study, the primary analysis of progression-free survival and objective response rate confirmed the robust single-agent activity of abemaciclib in heavily pretreated HR-positive, HER2-negative metastatic breast cancer, and found no significant improvement with the addition of tamoxifen.

However, Hamilton presented new overall survival data at the meeting, which showed that the addition of tamoxifen to abemaciclib provided a statistically significant median overall survival improvement compared to abemaciclib monotherapy in these patients. Progression-free survival was consistent with the primary results of nextMONARCH, with no significant difference.

Final overall survival analysis occurred 24 months after the last patient entered treatment. At the time of data cutoff on June 28, 2019, 12 of the 234 patients enrolled were still on the study treatment. At the median follow-up of 27.2 months, median overall survival was 24.2 months in the combination therapy arm, compared to 20.8 months in the abemaciclib 150 mg arm and 17 months in the abemaciclib 200 mg arm.

Hamilton also noted that the overall survival benefit was consistent across patient subgroups, including those with liver metastases, and those who had received prior tamoxifen for advanced or metastatic disease.

In a different presentation, Fabrice André of the Institut Gustave Roussy showed overall survival results from the Phase III SOLAR-1 study of alpelisib (Novartis' Piqray) plus fulvestrant for HR-positive, HER2-negative advanced breast cancer.

Around 40 percent of patients with HR-positive, HER2-negative advanced breast cancer patients have PIK3CA mutations, which are associated with poor prognosis, including reduced survival, André said.

SOLAR-1 showed that alpelisib — which is a PI3Kα inhibitor — combined with fulvestrant, significantly improved progression-free survival in patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer, compared with fulvestrant plus placebo. The researchers also presented the first interim overall survival results, but noted that these data were immature.

For the study, 572 men and postmenopausal women with HR-positive, HER2-negative advanced breast cancer, with no prior chemotherapy treatment and whose disease progressed on or after aromatase inhibition were randomized one-to-one to receive alpelisib plus fulvestrant, or fulvestrant plus placebo. The patients were also stratified by the presence of lung and/or liver metastases and prior use of CDK4/6 inhibitors.

Median progression-free survival was 11 months in the combination therapy arm compared to 5.7 months in the monotherapy arm. With a median follow-up of 30.8 months, the researchers observed a median overall survival of 39.3 months in the combination therapy arm compared to 31.4 months in the monotherapy arm. Median time to the start of chemotherapy was 23.3 months for the combination therapy cohort and 14.8 months for the monotherapy cohort. In patients with lung and liver metastases, median overall survival was 37.2 months with the combination compared to 22.8 months with the monotherapy.

Though overall survival hasn't yet reached statistical significance, it was prolonged by eight months when alpelisib was added to fulvestrant, which was clinically relevant, according to André. The statistically and clinically significant prolongation of progression-free survival "translated to numeric [overall survival] improvement," he said. "That supports the use of alpelisib in these patients with HR-positive, HER2-negative, PIK3CA-mutant advanced breast cancer, who present with poor prognosis."