What is the efficacy of combination therapy in the treatment of triple-negative breast cancer?

Updated: Feb 04, 2021
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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Unresectable metastatic triple-negative breast cancer (ie, estrogen receptor–negative, progesterone receptor–negative, and HER2 receptor–negative) is aggressive and carries a poor prognosis. However, combination therapy with the programmed cell death ligand–1 (PDL1) inhibitor atezolizumab plus nanoparticle albumin-bound (nab)–paclitaxel has been shown to prolong PFS in these patients. [157]  In March 2019, FDA approved atezolizumab in combination with nab-paclitaxel for triple-negative breast cancer. [158]

Approval was based on the phase III IMpassion130 trial in patients with untreated metastatic triple-negative breast cancer, in which intention-to-treat analysis showed median PFS of 7.2 months with atezolizumab plus nab-paclitaxel versus 5.5 months with placebo plus nab-paclitaxel (hazard ratio [HR] for progression or death, 0.80; 95% confidence interval [CI], 0.69 to 0.92; P=0.002); in patients with PDL1-positive tumors, median PFS was 7.5 months and 5.0 months, respectively (HR, 0.62; 95% CI, 0.49 to 0.78; P< 0.001). [157]

However, subsequent study results have placed the status of this combination in jeopardy. In September 2020 the FDA issued an alert that atezolizumb plus paclitaxel is ineffective in patients with previously untreated, inoperable, locally advanced or metastatic triple-negative breast cancer. The alert was based on findings from the phase III IMpassion131 trial showing that atezolizumab plus paclitaxel did not significantly reduce the risk of cancer progression and death, when compared with paclitaxel plus placebo, in PD-L1–positive patients. Interim overall survival results in IMpassion131 also favored paclitaxel plus placebo over paclitaxel plus atezolizumab in both the PD-L1–positive and the total study population. The FDA advised that "continued approval of atezolizumab in combination with [nab-paclitaxel] may be contingent on proven benefit of the treatment in additional trials." [159]

Since metastatic triple-negative breast cancer is aggressive, it is important to have multiple treatment options. On April 22, 2020, the FDA granted accelerated approval to the first antibody-drug conjugate, sacituzumab govitecan-hziy (Trodelvy), for metastatic triple-negative breast cancer in patients who have received at least two prior therapies for metastatic disease.

Approval was based on the multicenter, single-arm IMMU-132-01 trial (n=108), in which patients treated with sacituzumab every 21 days had an ORR of 33.3% (95% CI: 24.6, 43.1) and a median duration of response of 7.7 months (95% CI: 4.9, 10.8). [160]

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