Impassion132 Phase Iii Trial: Atezolizumab And Chemotherapy In Early Relapsing Metastatic Triple-Negative Breast Cancer

Abstract

The PD-L1 inhibitor atezolizumab received US FDA accelerated approval as treatment for PD-L1-positive metastatic triple-negative breast cancer (TNBC). In IMpassion130, combining atezolizumab with first-line nab-paclitaxel for metastatic TNBC significantly improved progression-free survival and showed a clinically meaningful effect on overall survival in patients with PD-L1-positive tumors. The placebo-controlled randomized Phase III IMpassion132 (NCT03371017) trial is evaluating atezolizumab with first-line chemotherapy (capecitabine [mandatory in platinum-pretreated patients] or gemcitabine/carboplatin) for inoperable locally advanced/metastatic TNBC recurring ≤12 months after completing standard (neo)adjuvant anthracycline and taxane chemotherapy. Stratification factors are: visceral metastases, tumor immune cell PD-L1 status and selected chemotherapy. Patients are randomized to atezolizumab 1200 mg or placebo every 3 weeks with the chosen chemotherapy, continued until progression, unacceptable toxicity or withdrawal. The primary end point is overall survival.

Phase II study of pembrolizumab and capecitabine for triple negative and hormone receptor-positive, HER2−negative endocrine-refractory metastatic breast cancer

“…28 Results from the phase III IMpas-sion132 trial evaluating atezolizomib with several chemotherapies including capecitabine as first-line therapy for TN MBC will contribute to our understanding of the use of chemo-immunotherapy in metastatic TNBC. 29 For HR+ endocrine-refractory MBC, there is more limited data for chemo-immunotherapy. One phase II study of eribulin and pembrolizumab compared with pembrolizumab alone demonstrated no improvement in PFS.…”

Aptamer targeted therapy potentiates immune checkpoint blockade in triple-negative breast cancer

“…Nevertheless, thanks to of the continuous effort in searching molecularly targeted approaches for TNBC, the first targeted therapies have been recently approved. These consist in the PARP inhibitors Olaparib or Talazoparib [6], which is beneficial for BRCA-mutated patients but efficiently target TNBC cells regardless of the BRCA-status, and the anti-programmed cell death-ligand 1 (PD-L1) Atezolizumab plus nab-paclitaxel chemotherapy [7], which applies to patients with unresectable locally advanced or metastatic PD-L1-positive TNBCs.…”

<p>Progress: Targeted Therapy, Immunotherapy, and New Chemotherapy Strategies in Advanced Triple-Negative Breast Cancer</p>

“…However, IMpassion 132 (NCT03371017) focuses on patients with early relapsing TNBC and evaluates the efficacy and safety of combining atezolizumab with non-taxane (gemcitabine plus carboplatin or capecitabine alone). 89 This trial should indicate whether similar improvements can be achieved with an alternative chemotherapy regimen in patients with early relapsing TNBC.…”