Novel Agents Spark New Approaches for Triple-Negative Breast Cancer

Christina T. Loguidice
Published: Thursday, Feb 14, 2019
Joyce A. O’Shaughnessy, MD

Joyce A. O’Shaughnessy, MD

Although triple-negative breast cancer (TNBC) remains challenging to treat, promising clinical trial findings are paving the way for new therapies. During a recent OncLive Peer Exchange®, a panel of breast cancer experts discussed emerging agents, which include an anti–PD-L1 antibody, 2 PARP inhibitors, and a novel antibody–drug conjugate.

The need for new strategies to treat TNBCs is particularly pressing. These tumors are associated with higher rates of relapse, greater metastatic potential, and shorter overall survival (OS) compared with most other breast cancer subtypes.1 Treatment options have been limited, as agents targeting specific molecular markers have often failed to achieve clinically meaningful improvements in outcomes. Subsequently, chemotherapy has remained the standard of care. Now, recent and pending FDA approvals may change that paradigm.

Immunotherapy Advances

IMpassion130 Findings

The combination of atezolizumab (Tecentriq) plus nab-paclitaxel (Abraxane) is undergoing FDA review as a frontline therapy for TNBC. In November 2018, the FDA granted the combination a priority review designation for this indication in patients with unresectable locally advanced or metastatic PD-L1–positive tumors, based on data from the phase III IMpassion 130 trial.2 The FDA is expected to make its decision by March 12, 2019.2 If approved, atezolizumab would become the first immune checkpoint inhibitor approved for the treatment of breast cancer. IMpassion 130 (NCT02425891) randomly assigned women with untreated metastatic TNBC (N = 902) to receive the anti–PD-L1 antibody atezolizumab plus standard chemotherapy with nab-paclitaxel (n = 451) or nab-paclitaxel plus placebo (n = 451).3 Patients were treated until disease progression or unacceptable toxicity. “The population was notable for a few different reasons, one of which is that 40% were treatment-naïve, so [it was] a higher population of de novo disease than one might normally expect in their own practice. And 40% of the patients were PD-L1 positive by the VENTANA assay, which directly impacts the interpretation of the results,” Heather L. McArthur, MD, MPH, said.

The study had 2 primary endpoints: progression-free survival (PFS) in both the intention-to-treat (ITT) population and the PD-L1– positive subgroup and OS in the ITT population, with OS formally assessed in the PD-L1–positive population only upon the ITT findings showing significance. At a median follow-up of 12.9 months, atezolizumab-treated patients in both subgroups had a statistically significant PFS benefit. In the ITT population, the median PFS was 7.2 months in the atezolizumab group versus 5.5 months in the placebo group (HR for progression or death, 0.80; 95% CI, 0.69-0.92; P = .0025). In the PD-L1–positive population, the median PFS was 7.5 months in the atezolizumab group and 5.0 months in the placebo group (HR, 0.62; 95% CI, 0.49-0.78; P <.001) (Table).3 “[This] 40% reduction [in risk of progression or death] was impressive,” McArthur said.

Table. Key Findings in IMpassion130 Trial3

Table. Key Findings in IMpassion130 Trial3 In contrast, the OS benefit in the ITT population did not reach statistical significance, with a median OS of 21.3 months in the atezolizumab group and 17.6 months in the placebo group (HR for death, 0.84; 95% CI, 0.69-1.02; P = .08). “Because the survival benefit seen in the intention- to-treat population was not significant, the trial investigators were not able to do formal testing; however, the improvement in overall survival in the PD-L1–positive subset was 9.5 months [25.0 months for atezolizumab-treated vs 15.5 months for placebo-treated], which is unprecedented. So this really represents an incredible innovation in an otherwise aggressive and devastating disease,” McArthur said, adding that the trial is “practice-changing.”

The panelists proceeded to express considerable excitement over the trial findings because atezolizumab plus nab-paclitaxel is the first immunotherapy and targeted treatment to show improved survival in patients with metastatic TNBC. “I didn’t think the results were going to be that good. I really thought that maybe we’d see some kind of PFS benefit, maybe longer in the PD-L1–positive population but no real OS benefits like we’re seeing now,” Adam M. Brufsky, MD, PhD, said. He added that the results were being driven by patients with PD-L1–positive tumors, as the greatest benefit was observed in this subset.

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: How Do We Leverage PARP Inhibition Strategies in the Contemporary Treatment of Breast Cancer?May 31, 20191.5
Community Practice Connections™: A Better Way to Stop Pain: Paths Toward Responsible Postsurgical Pain Management for Patients With Breast CancerMay 31, 20191.5
Publication Bottom Border
Border Publication