COMMENTARY

An 'Encouraging First Signal' for Breast Cancer Immunotherapy at ESMO 2018

Prof Peter Schmid FRCP, PhD, MD

Disclosures

October 22, 2018

I'm Peter Schmid, I'm a medical oncologist working at Bart's Hospital in London.

I'm going to discuss the data of the phase 3 trial IMpassion130 which was presented at ESMO 2018 held in Munich.

The IMpassion130 trial is a randomised phase 3 trial that was set up to investigate whether the addition of the immune checkpoint inhibitor atezolizumab to standard chemotherapy has a benefit in terms of prolonging progression-free survival and overall survival in patients with metastatic triple negative breast cancer.

It's a blinded phase 3 trial. Patients were randomised to either treatment with nab-paclitaxel and placebo, or nab-paclitaxel and atezolizumab.

It’s a first line study with patients with metastatic triple negative breast cancers. Patients were not allowed to have received prior chemotherapy for advanced disease. They were allowed to have received adjuvant or neoadjuvant chemotherapy, including taxanes, as long as the treatment-free interval was at least 12 months.

Stratification markers of the trial were PD-L1 expression. PD-L1 expression was defined as at least 1% staining on immune cells. Other stratification markers were presence of liver metastases or prior use of taxanes.

The trial had four co-primary endpoints. Two for progression-free survival. Progression free survival in the intention to treat population, which included all comers, and also progression-free survival in the PD-L1-positive patients which was about 40% of the overall population.

The other two co-primary endpoints were overall survival both in the ITT population and in the PD-L1- positive population

Presenting the Latest Data

At ESMO 2018, we presented the final data for progression-free survival both for the ITT and PD-L1+ population, and the first interim results for overall survival.

The study met its primary endpoint in terms of progression-free survival with a hazard ratio 0.80 for the ITT population, and a hazard ratio of 0.62 for the 41% of patients with PD-L1+ tumours. This led to a prolongation of progression-free survival from 5 months to 7 and a half months in the group of patients with PD-L1-positive tumours.

At the time of the analysis 60% of the required overall survival events had occurred. In the ITT population, overall survival was not statistically significant according to the pre-specified boundaries.

Looking at overall survival in patients with PD-L1+ tumours there was a clear difference in median overall survival with 15.5 months for patients receiving placebo compared to 25 months for patients receiving atezolizumab. The hazard ratio was 0.62 Formal statistical testing was not performed due to the hierarchical statistical design.

Looking at the exposure to the study drugs, there was no decrease in the dose intensity for nab-paclitaxel associated with the use of atezolizumab. The safety profiles were largely comparable although there was slightly higher rate of toxicities in the atezolizumab arm compared to placebo.

Most of the side effects observed were down to chemotherapy. There was a slightly higher rate of peripheral neuropathy in the atezolizumab arm which we attributed to a longer duration of treatment with nab-paclitaxel compared to the placebo arm.

Setting New Standards

Overall, this is the first study with immune therapy breast cancer to demonstrate a positive outcome. It is also the first trial of a targeted therapy in metastatic triple negative breast cancer to demonstrate an improvement in overall survival.

The trial met its endpoint and progression-free survival both for the ITT and PD-L1+ population, improving the hazard ratio to 0.80 and 0.62 for the PD-L1+ population.

The trial also shows a survival benefit going from 15.5 months to 25 months in patients with PD-L1+ tumours. Safety results were comparable and expected in keeping with what we know from the agents atezolizumab and nab-paclitaxel.

The trial should be one of the new standards for patients with PD-L1+ tumours showing that patients should receive treatment with immune checkpoint inhibitor nab-paclitaxel if there's an indication for taxane therapy.

'Encouraging First Signal'

The results of the IMpassion130 trial will be used to hopefully obtain regulatory approval in different countries. Once regulatory approval is obtained I would consider this as a new standard for patients who have PD-L1+ tumours with metastatic triple negative breast cancer.

We will also expect to get a follow up of the survival data over the months to come and we'll see whether there is change in the outcome for patients in the ITT population.

In addition, immune checkpoint inhibitors are moving into early breast cancer. We would expect results from the first phase 3 trials to be available in the next year to come.

Overall, this is the first step of introducing immune therapy into the treatment of triple negative breast cancer. For me personally it is a very encouraging first signal that gives me a lot of hope. We will have to wait for the final results in overall survival, and also are keen to see the results of trials in early breast cancer that will further define the role of immune therapy in patients with triple negative breast cancer. Thank you very much.

 

References

The study was funded by F. Hoffmann–La Roche/Genentech. Prof Schmid has reported receiving honoraria from AstraZeneca, Bayer, Boehringer, Celgene, Eisai, Novartis, Pfizer, Puma, Roche/Genentech. He has received grants or been supported/had contracted research from Astellas, AstraZeneca, Medivation, Novartis, OncoGenex, Roche/Genentech (all paid to his institution). His wife is an employee of Roche.  Disclosures for the other authors are listed in the article.

European Society for Medical Oncology (ESMO) 2018 Congress. Presented October 20, 2018. Abstract LBA1.

N Engl J Med. Published on October 20, 2018. Abstract

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