Monitoring Metastatic Breast Cancer Treatment Response: 5 Things to Know

Victoria Stern

Disclosures

November 23, 2020

The 5-year survival estimates for women with metastatic breast cancer (MBC) hover around 28%, according to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data from 2010 to 2016. But closer scrutiny of the evolution of MBC care reveals a more promising outlook, according to Adam Brufsky, MD, PhD, associate chief of the Division of Hematology/Oncology and co-director of the Comprehensive Breast Cancer Center at the University of Pittsburgh School of Medicine.

A 2017 analysis found that between 1992-1994 and 2005-2012, the 5-year relative survival doubled from 18% to 36% for younger women. And some patients with MBC live 10 years or more with the condition. "No one will deny that MBC is serious and ultimately fatal, but today, oncologists have so many more tools at our disposal to extend a patient's life 5, 10 years and hopefully longer," Brufsky said.

Despite this progress, Lisa A. Carey, MD, noted that there's still a long road ahead to understanding how the disease progresses and why some patients respond well to treatment while others do not.

"We've come far in terms of survival, but some subgroups of patients benefit more than others," said Carey, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research, chief of the Division of Hematology/Oncology, and deputy director of clinical sciences at University of North Carolina-Chapel Hill. "We still need a better understanding of what resistance is, what causes it, and how we can better predict treatment response."

Here are five things to know about monitoring treatment response in MBC.

1. MBC is moving towards chronic condition status.

Targeted agents and immunotherapy drugs emerging on the treatment landscape for three major types of MBC — estrogen (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative tumors — have continued to move the needle on survival.

In April, the US Food and Drug Administration (FDA) approved the tyrosine kinase inhibitor (TKI) tucatinib to treat HER2-positve MBC in combination with trastuzumab and capecitabine. The approval was based on safety and efficacy data from a phase 3 trial which revealed a 1-year progression-free survival (PFS) of 33.1% in the tucatinib-combination group and 12.3% in the placebo-combination group. Perhaps most notable was the secondary outcome among patients with brain metastases, a notoriously challenging group to treat. The authors reported a 1-year PFS of 25% in the combination group compared with 0% in the placebo-combination group.

Last year, the FDA gave the PI3KCA inhibitor alpelisib the green light to treat men and postmenopausal women with hormone receptor (HR)-positive, HER2-negative, PIK3CA-mutated MBC. The approval was based on a phase 3 trial which found that patients with PIK3CA-mutated cancer who had already received endocrine therapy saw more benefit with alpelisib and fulvestrant than with placebo–fulvestrant. At a 20-month follow-up, PFS in the alpelisib combination group was 11 months vs 5.7 months in the placebo-drug group.

Regarding treatment of metastatic triple-negative tumors, a phase 3 trial published in 2018 found that the monoclonal antibody atezolizumab (which inhibits PD-L1) plus nab-paclitaxel extended PFS in patients with untreated MBC by 1.7 months compared with nab-paclitaxel and placebo (7.2 months vs 5.5 months, respectively). The PFS benefit widened slightly when patients with PD-L1–positive tumors received the targeted agent compared with the chemotherapy-placebo combination (7.5 months vs 5.0 months, respectively).

"Although we can't classify MBC as a chronic condition yet, we've been chipping away at the disease for decades, and I feel hopeful that we're getting closer to that vision," Brufsky said.

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