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ESMO 2018: IMpassion 130: Atezolizumab Plus Nab-Paclitaxel in Metastatic Triple-Negative Breast Cancer

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Key Points

  • The combination therapy reduced the risk of disease worsening or death by 20% in all patients and 38% in the subgroup expressing PD-L1.
  • In patients with PD-L1–positive tumors, the median overall survival was 25.0 months with the combination compared to 15.5 months with standard chemotherapy alone.
  • The objective response rate was higher with the combination compared to chemotherapy alone for all patients (56% vs 46%) and those with PD-L1–positive tumors (59% vs 43%).

A combination of immunotherapy and chemotherapy improves survival in some patients with metastatic triple-negative breast cancer, according to late-breaking results from the IMpassion130 trial reported by Schmid et al at the European Society for Medical Oncology (ESMO) 2018 Congress (Abstract LBA1_PR).

Peter Schmid, FRCP, MD, PhD, first author of the study, said in a statement that the results “will change the way triple-negative breast cancer is treated.… Atezolizumab [Tecentriq] in combination with [nanoparticle albumin-bound (nab)]-paclitaxel [Abraxane] is the first targeted treatment to improve survival in metastatic triple-negative breast cancer,” said Dr. Schmid, Clinical Director of London’s St. Bartholomew’s Breast Cancer Centre, Barts Health NHS Trust, and Lead of the Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London. “It is also the first immune therapy to improve outcome in this cancer. Most of the survival benefit was in patients with [programmed cell death ligand 1] (PD-L1)–positive tumors.”

The phase III IMpassion130 trial enrolled 902 patients with metastatic triple-negative breast cancer who had not received prior treatment for metastatic disease. Patients were randomly allocated to standard chemotherapy (nab-paclitaxel) plus atezolizumab, an antibody targeting the protein PD-L1, or to standard chemotherapy plus placebo. The co-primary endpoints were progression-free survival and overall survival. The median follow-up was 12.9 months.

IMpassion130 Results

The combination therapy reduced the risk of disease worsening or death by 20% in all patients and 38% in the subgroup expressing PD-L1. In the entire study population, the median progression-free survival was 7.2 months with the combination and 5.5 months with chemotherapy alone (hazard ratio [HR] = 0.80, P = .0025). In the PD-L1–positive group, the median progression-free survival was 7.5 months with the combination and 5.0 months with chemotherapy alone (HR = 0.62, P < .0001).

More than half of patients were alive at the time of analysis, so this was an interim assessment of overall survival. In patients with PD-L1–positive tumors, the median overall survival was 25.0 months with the combination compared to 15.5 months with standard chemotherapy alone (HR = 0.62). In all patients, survival was 21.3 months with the combination vs 17.6 months with chemotherapy alone, which was not statistically different, likely because of the short follow-up.

The objective response rate was higher with the combination compared to chemotherapy alone for all patients (56% vs 46%) and those with PD-L1–positive tumors (59% vs 43%).

Safety Profile

Dr. Schmid said the combination therapy was well tolerated. Most side effects were due to chemotherapy and occurred at a similar rate in both treatment groups, although there was a minor increase in nausea and cough in the combination group. Side effects related to immune therapy were rare, the most common being hypothyroidism, which occurred in 17.3% of patients receiving the drug combination and 4.3% receiving chemotherapy alone.

Dr. Schmid concluded, “Immune therapy on top of standard chemotherapy prolonged survival by 10 months in patients with tumors expressing PD-L1. This combination should become a new treatment option for patients with metastatic triple-negative breast cancer.”

Commentary

Commenting on the results, Marleen Kok, MD, PhD, medical oncologist at the Netherlands Cancer Institute, said in a statement, “This is the first randomized phase III trial providing evidence that adding immune therapy to standard chemotherapy increases progression-free survival in metastatic triple-negative breast cancer, particularly in patients with PD-L1–positive tumors, and extends overall survival in the PD-L1–positive subgroup. While the benefit in terms of progression-free survival was relatively small, around 3 months, the gain in overall survival in the PD-L1–positive subgroup was impressive, with a 10-month benefit. Around 40% of the tumors were PD-L1–positive. The IMpassion130 data will probably change the treatment landscape for our [patients with] metastatic triple-negative breast cancer.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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