Highlights from

ESMO 2020

European Society for Medical Oncology Congress 2020

Virtual 19 - 21 September 2020

Trials with chemoimmunotherapy in metastatic TNBC show contradicting results

After showing significant benefit in progression-free survival (PFS) for atezolizumab in metastatic triple-negative breast cancer (TNBC) patients, the final overall survival (OS) analysis of IMpassion130 also showed a clinical meaningful benefit in patients who are PD-L1-positive. However, in the Impassion131 trial, atezolizumab showed no PFS nor OS benefit.

Metastatic TNBC has a poor prognosis compared to other breast cancer subtypes. 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. This benefit was observed both in the ITT population and in PD-L1 immune cell-positive patients [1]. In the first and second interim overall survival (OS) analysis, a meaningful improvement was observed in the PD-L1-positive population, although not formally tested due to the pre-specified statistical analysis plan.

At ESMO Virtual 2020, Dr Leisha Emens (University of Pittsburgh, USA) presented the final OS analysis and long-term safety data of IMpassion130 [2]. Median 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. 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.

The phase 3 IMpassion131 trial elaborates on the IMpassion130 trial. In IMpassion131, 651 patients with metastatic or unresectable TNBC were 2:1 randomised to first-line treatment with atezolizumab plus paclitaxel or placebo plus paclitaxel. So, one difference between IMpassion130 and IMpassion131 is the chemo-backbone. Hierarchical testing was also different: the primary endpoint (PFS) was tested first in the PD-L1-positive population, then in the ITT population. At ESMO Virtual 2020, Dr David Miles (Imperial College London, UK) presented the results of the first interim analysis of IMpassion131 [3]. In the PD-L1-positive population, atezolizumab did not significantly improve PFS. Median PFS was 6.0 months in the atezolizumab arm and 5.7 months in the placebo arm (HR 0.82; P=0.20). Expected after that result, no benefit of atezolizumab in the ITT population could be observed either. Dr Miles showed that the lack of benefit of atezolizumab in IMpassion131 was not due to a difference in exposure to paclitaxel.

Commenting on both presentations, Dr Lisa Carey (University of North Carolina, USA) addressed 3 potential factors that could explain the different outcomes of IMpassion130 and IMpassion131 [4]. First, paclitaxel is administered in combination with steroids, which could compromise the effect of immunotherapy. However, Dr Carey showed, data from KEYNOTE-355 do not support this explanation. Second, there seems to be no apparent difference in the trial populations. This leaves play of change as a third potential explanation, concluded Dr Carey. She pointed out that the 95% CI limits for median PFS in both trial did overlap. “This is the reality of clinical research.”

  1. Schmid P, et al; IMpassion130 Trial Investigators. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. 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.
  4. Carey LA. A tale of two trials: atezolizumab in metastatic triple negative breast cancer. ESMO 2020 Virtual Meeting, Presentation ID 4800.

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.