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Contradicting results for chemoimmunotherapy in metastatic TNBC

ESMO 2020
Both IMpassion130 and IMpassion131 evaluated the effect of atezolizumab added to first-line chemotherapy in metastatic TNBC patients, but their results contradict.

Recently, the phase 3 IMpassion130 trial showed a significant benefit in progression-free survival (PFS) for inoperable metastatic TNBC patients who were treated in first-line with the combination of atezolizumab and nab-paclitaxel (HR 0.80; P=0.002) [1]. This benefit was observed both in the intention-to-treat (ITT) population and in PD-L1 immune cell-positive patients. Median overall survival (OS) in the ITT population was 21.0 months for the atezolizumab-treated patients and 18.7 months in the placebo arm (HR 0.87; P=0.77); 3-year OS was 28% and 25%, respectively [2]. Median OS in the PD-L1-positive patients was 25.4 months in the atezolizumab arm versus 17.9 months with placebo (HR 0.67; not formally tested); 3-year OS was 36% and 22%, respectively. In the PD-L1-negative population, there was no OS benefit for atezolizumab.

In contrast, results from the first interim analysis of the phase 3 IMpassion131 trial do not show a significant improvement of PFS or OS in the PD-L1-positive population [3]. In this trial, 651 patients with metastatic or unresectable TNBC were randomised (2:1) to first-line treatment with atezolizumab plus paclitaxel or placebo plus paclitaxel. Median PFS was 6.0 months in the atezolizumab arm and 5.7 months in the placebo arm (HR 0.82; P=0.20). The lack of benefit of atezolizumab in IMpassion131 was not due to a difference in exposure to paclitaxel.

  1. Schmid P, et al. N Engl J Med 2018;379:2108-2121.
  2. Emens LA, et al. IMpassion130: Final OS analysis from the pivotal phase III study of atezolizumab + nab-paclitaxel vs placebo + nab-paclitaxel in previously untreated locally advanced or metastatic triple-negative breast cancer. ESMO 2020 Virtual Meeting, abstract LBA16.
  3. Miles DW, et al. Primary results from IMpassion131, a double-blind placebo-controlled randomised phase III trial of first-line paclitaxel (PAC) ± atezolizumab (atezo) for unresectable locally advanced/metastatic triple-negative breast cancer (mTNBC). ESMO 2020 Virtual Meeting, abstract LBA15.

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