乌鸦传媒

Adding the investigational agent ipatasertib to paclitaxel failed to improve progression-free survival in patients with PIK3CA/AKT1/PTEN-altered advanced triple-negative breast cancer, according to results from the phase III IPATunity130 Cohort A trial presented at the virtual 2020 San Antonio Breast Cancer Symposium.

In this exclusive 乌鸦传媒 video, , of Cleveland Clinic, discusses the trial in relation to the LOTUS trial, and what it could mean for AKT inhibitors in metastatic breast cancer.

Following is a transcript of her remarks:

So this study is the analysis of IPATunity130 Cohort A, and this clinical trial builds off phase II results from the LOTUS trial. And the LOTUS trial looked at the combination of ipatasertib, or IPAT, in combination with paclitaxel chemotherapy compared to paclitaxel chemotherapy alone, in patients with metastatic triple-negative breast cancer.

These patients were all treated in the early metastatic setting, meaning in their first line of therapy for advanced disease. And in the LOTUS trial, there actually was a signal of improved overall survival with the combination of IPAT plus paclitaxel compared to paclitaxel and placebo.

So this phase III trial intended to look at that same general population with the same combination of chemotherapy plus IPAT, the AKT inhibitor. The thing that was different about the phase III trial is that it was limited to a biomarker-selected group of triple-negative patients, meaning those with either PIK3CA/AKT1 or PTEN pathway alterations.

In the phase II LOTUS trial, these patients were included, but metastatic triple-negative patients without biomarker alterations were also included. And the results of that study were reported for the unselected or intent-to-treat as well as the biomarker-elective population.

So here in IPATunity130, we saw the first reveal of the results for both progression-free survival and overall survival for patients treated with the combination of the AKT inhibitor and chemotherapy compared to the chemotherapy and placebo.

And pretty surprisingly what was found is that there was actually no difference in both progression-free survival and overall survival, despite this being a population that shouldn't have been enriched for results because of the biomarker selection.

So I think this is a little bit puzzling given what we saw from really encouraging phase II results. And in fact, this biomarker-selective population was done because in the phase II trial, patients that were positive for the biomarkers actually had a greater signal of response.

So I think that this leaves open the question of what to do with AKT inhibitors in metastatic breast cancer. Of course here in metastatic triple-negative breast cancer, I don't know that the story is over because we still have to contend with those positive phase II results. And it was actually positive phase II results across the two studies.

So I think we want to explain that more in their biomarker studies coming out of IPATunity130 that hopefully will show us maybe a sub-population within this clinical trial population that may benefit. It also leads to the idea that there is more heterogeneity among this group, even though clinically they're all grouped together as patients with metastatic triple-negative breast cancer.

So I think although the study results are a little disappointing, given what we saw in the phase II setting, hopefully we will be able to gain more information from this clinical trial population to find a group of patients where this drug has a meaningful impact.

And then I think the AKT story in metastatic breast cancer in general is still one that merits further exploration, as there are trials of these agents in also the metastatic hormone receptor positive space in which we might expect to see a different result.

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