Primary results from IMpassion131, a double-blind, placebo-controlled, randomised phase III trial of first-line paclitaxel with or without atezolizumab for unresectable locally advanced/metastatic triple-negative breast cancer

Abstract

Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.

Real-World Data from a Refractory Triple-Negative Breast Cancer Cohort Selected Using a Clinical Data Warehouse Approach

“…In the IMpassion130 trial, the median OS was 21.3 months in the atezolizumab-nab-paclitaxel group and 17.6 months in the placebo-nab-paclitaxel group [ 6 ]. Another phase III clinical trial, IMpassion131, documented a median OS of about 20 months in patients receiving paclitaxel with or without aztezolizumab [ 28 ]. This might be because these clinical trials did not include TNBC patients who might have experienced worse treatment outcomes.…”

Immunomodulating Therapies in Breast Cancer—From Prognosis to Clinical Practice

“…However, in PD-L1-positive patients, OS increased from 18 to 25 months (HR 0.71; 95% CI 0.54-0.94). Surprisingly, the recently presented IMpassion131 trial combining atezolizumab with conventional paclitaxel in advanced TNBC did not improve PFS or OS compared with placebo + paclitaxel [72]. Of 651 randomized patients, 45% had PD-L1-positive aTNBC.…”

“…In the PD-L1-positive population, atezolizumab and paclitaxel were associated with a more favorable unconfirmed overall response rate (63% vs. 55% for placebo-paclitaxel) and a longer median duration of response (7.2 and 5.5 months, respectively). Possible reasons for this apparent contrast with the benefit observed in IMpassion130 require further investigation, although several hypotheses (e.g., different taxanes and the role of steroids or imbalances in prognostic features or random results in a relatively small study) are under discussion [72,73].…”

Triple Negative Breast Cancer: A Mountain Yet to Be Scaled Despite the Triumphs

“…Similarly, Atezolizumab also targets PD-L1, and it has been approved to treat metastatic TNBC in combination with paclitaxel [107]. However, a recent study indicated that combination treatment of paclitaxel and atezolizumab did not elicit an improved outcome in TNBC patients compared to the placebo group [237]. Yet another study showed that the combination treatment with paclitaxel and atezolizumab resulted in an improved overall survival rate in TNBC patients with enriched PD-L1 compared to the placebo group [238].…”