IMpassion 130 trial results: Immunotherapy for metastatic breast cancer

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Published: 22 Oct 2018
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Prof Peter Schmid - St Bartholomew Hospital London, UK

Prof Peter Schmid speaks with ecancer at ESMO 2018 in Munich to discuss results from the IMpassion 130 trial of atezolizumab versus placebo in combinations with nab-paclitaxel to treat advanced and metastatic breast cancers.

The experimental combination of PD1 immunotherapy produced improvements in PFS and OS among PD-L1 positive patients, though no benefit was seen in PD-L1 negative patients.

Prof Schmid discusses the tolerability of the drug and the significance of immunotherapy entering breast cancer therapy options, and considers upcoming trials employing checkpoint immunotherapy.

For more on this data, watch his presentation of the trial results at a conference session here.

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.

The IMpassion 130 trial is a randomised phase III trial that was set up to test whether the addition of the immune checkpoint inhibitor atezolizumab could improve the outcome of patients treated with single agent nab-paclitaxel chemotherapy as a first line treatment for metastatic triple negative breast cancer. The trial randomised one to one patients to treatment with nab-paclitaxel and placebo or nab-paclitaxel and atezolizumab. Patients were not allowed to have had prior chemotherapy for metastatic triple negative breast cancer but could have received prior chemotherapy in the neoadjuvant or adjuvant setting as long as the treatment free interval was at least one year

The study had four co-primary endpoints, two for progression free survival, first in the intention to treat population and secondly in the PD-L1 positive population. PD-L1 positivity was defined as staining of at least 1% of the immune cells with a PD-L1 antibody. The other two co-primary endpoints were overall survival in the intention to treat population as well as in the PD-L1 positive population. A total of 902 patients entered the trial; at this time point we have the final results for progression free survival, both in the ITT and in the PD-L1 positive group. We were also presenting preliminary results for overall survival based on approximately 60% of the required events for this analysis.

The trial met its primary endpoint in the intention to treat population showing an improved progression free survival with a hazard ratio of 0.8. More importantly, the trial showed an increased benefit in terms of progression free survival in the PD-L1 positive subgroup which was 41% of patients with a hazard ratio of 0.62.

Looking at overall survival, there was no statistically significant difference at this point in time with a hazard ratio of 0.84 which did not meet the pre-defined statistical significance level. As per hierarchical testing we could not do formal testing in the PD-L1 positive group but the results clearly show the median survival went up from 15.5 months in the placebo group to 25 months in the atezolizumab group which is a substantial benefit with a hazard ratio of 0.62.

Looking at the tolerability of the treatment, both treatment arms were relatively comparable with a slight increase in some toxicities in the combination treatment with atezolizumab but overall the treatments were well tolerated and the side effects observed were in keeping with what we know for single agent atezolizumab and single agent nab-paclitaxel.

The IMpassion130 trial is the first phase III trial to demonstrate a clear benefit of immune therapy in breast cancer. It is also the first phase III trial to demonstrate a substantial survival benefit for a targeted therapy for patients with metastatic triple negative breast cancer. It clearly improved progression free survival with a hazard ratio of 0.8 in the ITT population but a hazard ratio of 0.62 in the PD-L1 positive population. The trial clearly taught us that patients who had most likely benefit from immune therapy in triple negative breast cancers are the group of patients who have PD-L1 expression on immune cells. Overall survival data at this point are immature for the overall population but there’s a clear benefit in the PD-L1 positive group, improving survival from 15.5 months to 25 months.

You mentioned this is the first immunotherapy in this space, do you think it’s just the first of many to come?

The IMpassion130 trial is the first phase III trial in triple negative breast cancer but there are several phase III trials ongoing at the moment. In metastatic triple negative breast cancer these other phase III trials are investigating other chemotherapy backbones, for example paclitaxel, for example platinum-based therapy, they are also exploring other immune checkpoint inhibitors, for example pembrolizumab. We expect some of those results to become available in the next year. In addition there are other combination trials ongoing that investigate new combinations, for example with small molecules or other immune modulating agents. Again we expect first results in the next couple of years.

We also started trials in other subtypes of breast cancer, for example in hormone driven breast cancer or in HER2 positive breast cancer, early results are encouraging but a lot of work is still required. For me personally most importantly we are expecting the first results from neoadjuvant trials in triple negative breast cancer in the next year. There are two randomised phase III trials reading out, one with atezolizumab, one with pembrolizumab, which combine immune checkpoint inhibitors with neoadjuvant chemotherapy. If those trials were positive they would make a significant contribution to improving outcomes for patients with metastatic or with early triple negative breast cancer.