IMpassion130: Atezolizumab and nab-paclitaxel in triple-negative breast cancer

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Published: 22 Sep 2020
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Prof Leisha Emens - University of Pittsburgh, Pittsburgh, USA

Prof Leisha Emens spoke to ecancer online about the IMpassion130 trial presented at ESMO 2020.

The IMpassion130 trial is an exploratory analysis of atezolizumab and nab-paclitaxel for patients with triple-negative breast cancer.

She outlined the reasoning and background of the trial before outlining some of the results thus far.

Pro Emens also discussed toxicities and the next steps for IMpassion130.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.

IMpassion130 is a global randomised double-blind placebo-controlled clinical trial evaluating the addition of the anti-PD-L1 monoclonal antibody atezolizumab to the chemotherapy drug nab-paclitaxel. It focuses on patients with locally advanced, incurable or metastatic triple negative breast cancer who have not been treated for their advanced disease although they could have had chemotherapy in the curative setting provided the treatment free interval was 12 months or longer.

Triple negative breast cancer was focussed on as a clinical space to develop immunotherapy because it is more likely to have evidence of immune activation than other breast cancer subtypes. Until very recently it really represented a major, major unmet clinical need because really the only drugs we’ve had available have been chemotherapy historically. Now we’re very fortunate to have a number of targeted agents that are showing evidence of clinical activity in this space including PD-1 and PD-L1 blockade.

What methods did you use?

In IMpassion130 902 patients were equally randomised to receive either atezolizumab or placebo in combination with nab-paclitaxel. They continued their assigned treatment until disease progression or intolerable toxicity. The study had four pre-specified co-primary endpoints: progression free survival and overall survival in the intent to treat patient population and in the PD-L1 positive population where PD-L1 positivity is defined as PD-L1 expression in immune cells occupying at least 1% of the tumour area by the assay SP142 which is an immunohistochemistry assay.

The study had a hierarchical statistical design with overall survival where the study had to show statistical significance in the intent to treat patient population in order to formally test the impact of atezolizumab in the PD-L1 immune cell positive patient population. Stratification factors included liver metastases and PD-L1 immune cell expression as well as prior taxane therapy.

What did you find?

What we found in the study is that the study arms are quite well balanced with 451 patients in each arm. About 40% of the patients were PD-L1 immune cell positive and about half had received prior taxane therapy. At the first analysis the study showed a statistically significant improvement in progression free survival in both the intent to treat and particularly in the PD-L1 immune cell patient population where patients with PD-L1 positive advanced triple negative breast cancer had a 2.5 month improvement in progression free survival.

At ESMO this year we presented the final overall survival analysis and what that showed is that there continues to be an overall survival benefit that’s clinically meaningful, specifically in the PD-L1 immune cell positive patient population. At the first analysis we did not see a statistically significant benefit in the intent to treat patient population but there was almost a 10 month improvement in overall survival in the PD-L1 immune cell patient population. We did not formally test that but the magnitude of that benefit is quite clinically meaningful.

Now, at this final overall survival analysis we see a 7.5 month improvement in overall survival specifically in the PD-L1 immune cell patient population. That again cannot be formally tested statistically due to the hierarchical design but it’s quite a meaningful improvement in overall survival for this particular patient population. If you look at three-year overall survival rates for the control patient population it’s 22% and it increases actually to 36% in the immune cell PD-L1 positive patient population. So this agent has one of the few capabilities of prolonging survival for those patients who are fortunate enough to respond to it.

From a safety point of view the drug is quite well tolerated. In the group of patients who received atezolizumab with nab-paclitaxel there were greater numbers of adverse events including serious adverse events and immune related adverse events but these tend to be of low grade and generally didn’t result in treatment discontinuation. The exception to this was the development of neuropathy in patients who continued to receive nab-paclitaxel but that was not an immune related event and you could simply discontinue the chemotherapy.

So, overall, patients fortunate enough to respond live longer, enjoy a good quality of life and are able to maintain their functioning in the roles that are important to them. So overall a very good treatment option for the patients who have PD-L1 positive triple negative breast cancer.

What are the clinical implications of this study?

Currently right now the combination of atezolizumab and nab-paclitaxel is approved by health authorities in many parts of the world for patients with incurable triple negative breast cancer that is PD-L1 positive. Given the fact that we do see a clinically meaningful benefit in overall survival I’m hopeful that that will continue to remain an option for patients because it’s quite striking how well patients who benefit from this drug continue to do while receiving it.