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2019 ASCO-SITC: Combination Immunotherapy for Breast Cancer With Trastuzumab and a HER2-Targeted Vaccine

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Key Points

  • Concurrent trastuzumab plus nelipepimut-S and GM-CSF was safe, with no added overall or cardiac toxicity compared to treatment with trastuzumab and GM-CSF alone.
  • In the intention-to-treat analysis, the estimated disease-free survival was favorable but did not reach significance with the new combination regimen compared with trastuzumab and GM-CSF.
  • However, in patients with triple-negative breast cancer, there was a statistically significant improvement in disease-free survival with trastuzumab plus nelipepimut-S and GM-CSF.

After preclinical findings showed shared activity between trastuzumab and HER2-targeted vaccines, researchers evaluated adjvuant nelipepimut-S plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with trastuzumab compared to trastuzumab with GM-CSF alone in patients with HER2 low-expressing breast cancer. When a planned interim analysis showed a treatment benefit in patients with triple-negative breast cancer, the decision was made to close the trial with guidance from the independent data and safety monitoring board. At the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium, Hickerson et al reported the final analysis of the trial with 7 months of added follow-up (Abstract 1).

Trial Methods

A total of 275 patients were enrolled in the phase IIb trial and randomly assigned to receive placebo with GM-CSF or nelipepimut-S with GM-CSF. All enrolled patients also received trastuzumab once every 3 weeks for 1 year. GM-CSF or nelipepimut-S plus GM-CSF were given every 3 weeks for 18 weeks, starting with the third dose of trastuzumab, and boosters were given every 6 months for 24 months.

There were no clinicopathologic differences between the treatment groups. All patients enrolled were clinically disease-free patients with breast cancer who had been treated with standard therapy. They were diagnosed with HLA-A2, A3, A24, and/or A26-positive disease, had HER2-low expressing breast cancer, and were node-positive and/or had triple-negative breast cancer. The primary outcome was disease-free survival at 24 months.

Findings

Concurrent trastuzumab plus nelipepimut-S and GM-CSF was safe, with no added overall or cardiac toxicity compared to treatment with trastuzumab and GM-CSF alone. There were no grade 4/5 toxicities with the combination regimen. In the intention-to-treat analysis, the estimated disease-free survival was favorable but did not reach significance with the new combination regimen compared with trastuzumab and GM-CSF (hazard ratio [HR] = 0.62, 95% confidence interval [CI] = 0.31–1.25; P = .18). However, in patients with triple-negative breast cancer, there was a statistically significant improvement in disease-free survival with treatment with trastuzumab plus nelipepimut-S and GM-CSF [HR = 0.26, 95% CI = 0.08–0.81; P = .013).

The authors concluded, “The combination of nelipepimut-S with trastuzumab is safe with no added toxicity compared to trastuzumab alone, even after prolonged exposure. In this final analysis, there was a trend toward benefit in the intention-to-treat population that improved since the interim analysis with added follow-up. The significant benefit seen at interim in [patients with triple-negative breast cancer] continued to strengthen in the group [treated with the new combination]. These findings could position the nelipepimut-S plus trastuzumab combination as an adjuvant therapy for early-stage triple-negative breast cancer and warrant further study.”

Disclosure: The study authors' full disclosures can be found at coi.asco.org.

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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