Guideline: FDA approves an immunotherapy treatment for some patients with triple-negative breast cancer

IN-DEPTH REVIEW OF RESEARCH

Study background:

Triple-negative breast cancer (TNBC) accounts for approximately 15–20% of all breast cancers. TNBC is associated with earlier age of onset, aggressive clinical treatments, and a poorer prognosis compared to hormone receptor- and HER2-positive breast cancers. Given the lack of effective treatments for TNBC, researchers have focused on increasing the therapeutic options for TNBC patients.

The immune system has a key influences on the course of TNBC. Clinical trials have sought to better understand and define the role of immune checkpoint inhibitors as a treatment for TNBC. (Immune system checkpoint inhibitors are drugs that prevent malignant cells from evading the immune system). The culmination of these studies was the phase III IMpassion 130 trial. The iMpassion 130 trial showed an overall survival benefit in patients with advanced TNBC who were treated with the immune checkpoint inhibitor atezolizumab in combination with chemotherapy compared to chemotherapy alone.

This XRAYS review provides an update on research that we first covered in 2017.

Researchers of this study wanted to know:

Whether the combination of the PD-L1 inhibitor atezolizumab (Tecentriq) and nab-paclitaxel (Abraxane) compared to nab-paclitaxel alone increased progression-free survival in patients with locally advanced or metastatic TNBC. Progression-free survival is the period when a cancer doesn’t grow.

Population(s) looked at in the study:

Patients with untreated metastatic TNBC who participated in the IMpassion130 trial were randomly assigned to receive atezolizumab plus nab-paclitaxel (451 patients) or placebo plus nab-paclitaxel (452 patients).  Patients continued their treatment regimens until their disease progressed or an unacceptable level of side effects occurred. Median follow-up  timewas 12.9 months.

Researchers looked at the data from patients by the following groupings:

• whether they did or did not receive neoadjuvant or adjuvant nab-paclitaxel therapy
• the presence or absence of liver metastases at the beginning of the clinical trial.
• whether or not their tumor expressed programmed death ligand 1 (PD-L1) protein at the beginning of the clinical trial.

The two primary trial goals were to determine progression-free survival (the time before tumors grew) in the population treated with atezolizumab and PD-L1-positive subgroup, and overall survival (the time before death) in the population treated with atezolizumab. If the findings related to overall survival were significant, they would then look at the impact of this treatment on the overall survival in the PD-L1-positive subgroup.

Study findings: 

Patients who received the combination therapy showed a clinically meaningful median PFS of 7.2 months compared to 5.5 months with chemotherapy alone. One-year progression-free survival rates were 29% and 16% respectively. Among patients with PD-LI-positive tumors, median progression-free survival was 7.5 months and 5.0 months respectively.

Median overall survival was 21.3 months with combination therapy and 17.6 months with nab-paclitaxel alone. A positive overall survival outcome was achieved only in PD-L1-positve TNBC patients. In these patients, median overall survival was 25.0 months compared to 15.5 months for patients with PD-L1-negative tumors.

Almost 16% of patients who received the combination therapy had to stop treatment due to adverse effects, compared to 8.2% of those receiving nab-paclitaxel alone.

Limitations:

The results of IMpassion130 offer hope for immunotherapy as effective treatment of metastatic TNBC. However, researchers raised a number of questions including which tumors should be tested for PD-L1 expression, whether nab-paclitaxel is the best chemotherapy to be used with atezolizumab, and whether atezolizumab alone may be best for some patients.

Conclusions:

Treatment with atezolizumab plus nab-paclitaxel increased progression-free survival in patients with metastatic TNBC whose tumors were PD-L1-positive. 

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Posted 5/26/19