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Aug 22, 2019

Welcome to the ASCO Daily News Podcast. I'm Lauren Davis, and joining me today is Dr. Karen Tedesco of New York Oncology Hematology to discuss the impassioned 130 results in triple negative breast cancer. Today, we are discussing this aggressive form of breast cancer that is particularly difficult to treat because it's unresponsive to hormone and HER2-targeted therapies, leave patients with limited treatment options and a poor prognosis. Dr. Tedesco, welcome to the podcast.

Thank you, Lauren. It's a pleasure to be here.

An important treatment advance came in March 2019 when the FDA granted accelerated approval of atezolizumab, the first cancer immunotherapy regimen for breast cancer. Could you speak to the phase 3 and IMpassion 130 results, which led to the approval of this drug, in addition to the broader treatment landscape?

Yes, so the IMpassion 130 trial was a multi-center, international, double-blind, placebo-controlled randomized trial that included 902 patients who had locally advanced or unresectable metastatic breast cancer that had the triple negative profile, the ER, PR, and HER2 all being negative. The patients could not have received chemotherapy for metastatic disease previously, but could have received chemotherapy in the adjuvant setting, including a taxane, as long as it was a year or more prior to enrollment in this study.

And the study looked at the atezolizumab or a placebo given on days 1 and 15 every 28 days in conjunction with Nanoparticle Albumin-Bound, or NAB, paclitaxel at 100 milligrams per meter squared given on days 1, 8, and 15 of an every 28-day cycle. And they prospectively assessed for PD-L1 expression and called positive anything that expressed over 1% of the tumor area staining for the PD-L1 was considered a positive.

And in patients whose tumors expressed the PD-L1, the median progression-free survival was 7.4 months for the treatment arm, including the atezolizumab and NAB paclitaxel, and 4.8 months for those that received the NAB paclitaxel plus placebo. The progression-free survival hazard ratio was 0.6 with a p value of less than 0.001 in favor of the treatment arm with the atezolizumab.

The objective response rate was 53%, as compared to 33% for patients who received the atezolizumab and those who received the placebo. The overall survival data was not mature at this time, but when this trial was published in the New England Journal of Medicine in October of 2018, for the intention to treat population, median overall survival was 21.3 months with the atezolizumab and NAB paclitaxel compared to 17.6 months for the NAB paclitaxel and placebo.

And for patients who had tumors that were PD-L1-positive, the median overall survival was 25 months for those who received the atezolizumab with the NAB paclitaxel as opposed to 15.5 months for those who received the NAB paclitaxel and placebo.

So I'm curious. Do patients have immediate access to this treatment?

Yes, they do. I've ordered this for a couple of my patients now since the time of this approval, and I've not had any difficulties in terms of getting approval for the medication. I will say, particularly for those of us in smaller communities, I think the biggest obstacle is getting the PD-L1 testing done and communicating with pathologists about the particular companion diagnostic test, the Ventana PD-L1 Assay that was approved in conjunction with approval of this regimen.

So for me, I think that's been the biggest delay in access for the patients. But when I've ordered the medications, they were able to get them right away.

That's great. We always wonder about side effects, so what should specialists tell their patients?

So many of the most common side effects on this trial were actually those that we would probably think of as being more typical of the NAB paclitaxel, so alopecia, peripheral neuropathies, nausea, fatigue, neutropenia, decreased appetite. Certainly with any of the immune therapies, as many of us are getting more familiar, there are some toxicities we have to be aware of that are different than typical chemotherapy, and those largely include autoimmune-mediated toxicities

So in this particular trial, there were some autoimmune-mediated hypothyroidism episodes, and those can be pretty easily managed. There was one autoimmune hepatitis that was quite severe. Other autoimmune toxicities I think we need to be mindful of include pneumonitis and colitis, both of which were rare on this trial. And rashes can be another thing.

So even though this is the first immunotherapy approved for breast cancer treatment, many of us who treat other types of cancers out in the community are certainly gaining a lot of familiarity with these type of drugs. So I don't think anything was seen in terms of toxicities on this trial that was unanticipated.

That's good to know. Were there any surprises in the trial results?

I didn't think there were any surprises. I was happy to see that favorable results seemed to correlate with PD-L1 expression because again, I think that gives us a marker to look at for our patients and hopefully be able to best advise patients, depending on their molecular testing, whether a treatment is likely to be helpful to them or not so that we're not subjecting someone to needless toxicity if they're not likely to get significant benefit from the addition of a new drug.

That's true. What do you think's on the horizon for breast cancer studies?

Well, I think in the realm of immunotherapy, certainly there are going to be other immunotherapy drugs, likely in combination with chemotherapy, that are being looked at. There's going to be more studies coming out about immunotherapies in the neoadjuvant setting, particularly for the triple-negative profile breast cancer because that complete pathologic response can be a good surrogate in some instances for other outcomes and can more rapidly generate information.

I think with triple-negative breast cancer in general, what we're learning more about is that we can't just lump all these patients with triple-negative profile together as if they're one homogeneous group just because they don't express estrogen, and progesterone, and HER2 receptors on their breast cancer. So some of these, I think we're trying to identify what makes them unique and what particular drugs might be good targets for them.

So some of these triple-negative profile breast cancers may have androgen receptor expression and potentially respond well to anti-androgenic hormonal therapies, like we would use in prostate cancer, so things like bicalutamide, or enzalutamide, or understudy. PARP inhibitors are being looked at more in the triple-negative profile breast cancers, particularly those for women who have germline BRCA mutations, and even those who may have somatic BRCA mutations, or other types of mutations like PALB2 in their tumor.

So as we're doing more gene expression profiles on tumor, that can help us identify some appropriate targets for these patients with this oftentimes difficult-to-treat profile of breast cancer.

Absolutely. Again, today my guest has been Dr. Karen Tedesco. Thank you so much for being on our podcast today.

Thank you, Lauren.

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