Atezolizumab Plus Nab-Paclitaxel Boost Metastatic Triple-Negative Breast Cancer Survival

The addition of atezolizumab to nab-paclitaxel results in significantly longer progression-free survival for patients with treatment-naïve metastatic triple-negative breast cancer, especially among those with PD-L1-positive disease

medwireNews: IMpassion130 trial results demonstrate significant survival benefits for patients with untreated metastatic triple-negative breast cancer given atezolizumab plus nab-paclitaxel compared with nab-paclitaxel alone, with the greatest gains noted in patients with tumours expressing programmed cell death ligand 1 (PD-L1).  

In intention-to-treat analysis of the full study population, the co-primary endpoint of progression-free survival (PFS) was significantly longer for the 451 patients given atezolizumab plus nab-paclitaxel than the 451 participants who received only the taxane, at 7.2 versus 5.5 months and a hazard ratio (HR) for progression or death of 0.80. 

But the greatest PFS benefit with the combination regimen was found among the 138 patients whose tumours tested positive at baseline for PD-L1 expression, defined as at least 1% expression on tumour-infiltrating cells. 

For this subgroup, PFS was 7.5 months versus 5.0 months for the 184 PD-L1-positive controls, giving a significant HR for progression or death of 0.62. 

The interim overall survival (OS) analysis, after a median of 12.9 months, was numerically better in the intention-to-treat population with atezolizumab plus nab-paclitaxel, at 21.3 versus 17.6 months for the taxane alone. 

The HR for death of 0.84 in the whole study population did not reach statistical significance and the study protocol did not call for subgroup OS analysis in this scenario. Nevertheless, greater benefit was found among PD-L1-positive patients, with corresponding durations of 25.0 and 15.5 months and a HR of 0.62, albeit this was not statistically tested. 

PD-L1-positive patients using atezolizumab plus nab-paclitaxel also achieved a numerically higher objective response rate than controls, at 58.9% versus 42.6%, with complete responses reported for 10.3% and 1.1%, respectively. 

Peter Schmid, from Barts Cancer Institute in London, UK, and co-authors say that “these data confirm phase 1 observations of improved outcomes in patients with high PD-L1 expression who were receiving atezolizumab, pembrolizumab, or avelumab.” 

Adverse events reported in the trial were “consistent with the known safety profiles of each agent”. Grade 3 or 4 events occurred in 48.7% of patients using atezolizumab plus nab-paclitaxel and 42.2% of controls, with peripheral neuropathy more common in the former group (5.5 vs 2.7%). 

Grade 3 or 4 adverse events of special interest – potentially immune-related side effects – occurred in 7.5% and 4.3% of patients in each arm, respectively, with one grade 5 event in each treatment group. 

The researchers therefore conclude that the trial “provides evidence of the efficacy of immunotherapy in at least a subset of patients”. 

They emphasize: “It is important for patients’ PD-L1 expression status on tumor-infiltrating immune cells to be taken into consideration to inform treatment choices for patients with metastatic triple-negative breast cancer.” 

The IMpassion130 results were presented at the ESMO 2018 Congress, held in Munich, Germany, and simultaneously published in The New England Journal of Medicine. 

 

References 

Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med; Advance online publication 20 October 2018.
DOI: 10.1056/NEJMoa1809615  

Schmid P, Adams S, Rugo HS, et al. IMpassion130: Results from a global, randomised, double-blind, phase 3 study of atezolizumab (atezo) + nab-paclitaxel (nab-P) vs placebo + nab-P in treatment-naive, locally advanced or metastatic triple-negative breast cancer (mTNBC). ESMO 2018 Congress, 19-23 October, Munich, Germany (LBA1_PR).

Abstract, slides and webcast on this presentation are available

Watch the ESMO Video Highlight interview on this study

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