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21-10-2018 | Triple-negative breast cancer | ESMO 2018 | News

IMpassion130 supports atezolizumab use in triple-negative breast cancer

medwireNews: Results for the IMpassion130 trial support the combination of atezolizumab and nab-paclitaxel for the treatment of metastatic triple-negative breast cancer, especially among patients with programmed cell death ligand 1 (PD-L1)-positive disease.

The progression-free survival (PFS) and overall survival (OS) findings were presented at the ESMO 2018 Congress, held in Munich, Germany, and simultaneously published in The New England Journal of Medicine.

Speaking to medwireNews, presenting author Peter Schmid, from Barts Cancer Institute in London, UK, said that the “IMpassion130 trial clearly establishes atezolizumab as a first-line treatment option for patients with metastatic triple-negative breast cancer and PD-L1-positive tumours.”

In intention-to-treat analysis, PFS was a median of 7.2 months for the 451 patients who were randomly assigned to receive atezolizumab 840 mg on days 1 and 15 of a 28-day cycle with nab-paclitaxel 100 mg/m2 given on days 1, 8, and 15.

This was significantly better than the median PFS of 5.5 months for the 451 patients who received only nab-paclitaxel, giving a hazard ratio (HR) for progression or death of 0.80.

Moreover, subgroups analysis showed that the 138 atezolizumab-treated patients who had PD-L1 expression of at least 1% on tumor-infiltrating cells derived greater PFS benefit, with a median duration of 7.5 months versus 5.0 months for the 184 PD-L1-positive patients given only nab-paclitaxel (HR=0.62).

Interim OS in the intention-to-treat population was performed after a median follow-up of 12.9 months and 60% of events, Schmid said.

Median OS was “numerically better” at this time with atezolizumab plus nab-paclitaxel than with nab-paclitaxel alone – at 21.3 versus 17.6 months – but the HR of 0.84 did not reach statistical significance.

The trial design precluded statistical analysis of the PD-L1-positive subgroup but the investigators report that the atezolizumab regimen achieved a median OS of 25.0 months compared with 15.5 months with nab-paclitaxel alone, with a HR of 0.62.

The objective response rate was also numerically higher with atezolizumab among the PD-L1-positive subgroup (58.9 vs 42.6%), including the rate of complete response (10.3 vs 1.1%).

Looking forward, Schmid said that he hoped that the intention-to-treat analysis would be positive for OS benefit with atezolizumab with longer follow-up, allowing formal analysis of the PD-L1-positive patients, but he expected that any “modest” OS gain in the whole group would be driven by a “substantial” benefit in the subgroup.

The safety analysis was “consistent” with earlier toxicity profiles for both drugs. Grade 3–4 events occurred in a comparable 48.7% of the atezolizumab arm and 42.2% of controls, albeit with a higher rate of peripheral neuropathy for the combination treatment arm.

Schmid commented to medwireNews that phase III trials are now underway to investigate other chemotherapy regimens, such as platinum or paclitaxel regimens, and other immune checkpoint inhibitors in the same population as IMpassion130.

“But in my opinion, most importantly, there are phase III trials ongoing that investigate the role of immune checkpoint inhibitors in early breast cancer,” he said.

“We have two randomized phase III trials, reading out probably in the next year, that investigate the addition of either pembrolizumab or atezolizumab to neoadjuvant […] chemotherapy in early triple-negative breast cancer,” Schmid continued.

“I think these data will be very important to further define the role of immune therapy in breast cancer.”

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group

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