Patient Profile 2: Patient with Triple-Positive mBC

Experts discuss the use of frontline therapy in patients with triple-positive metastatic breast cancer.

Neil Iyengar, MD:
Let’s move on to a second case. I’m going to present a patient of mine who is a 62-year-old, Caucasian female who originally presented in 2017 with a stage II triple-positive breast cancer, so hormone receptor-positive, HER2-positive. We treated her in the neoadjuvant setting with an anthracycline-based regimen of dose-dense AC [Adriamycin (doxorubicin)+Cytoxan (cyclophosphamide)]-T [Taxol (paclitaxel)] including Herceptin [trastuzumab] and pertuzumab [Perjeta] with the Taxol. She did fairly well with that regimen. Went on to have a mastectomy, which revealed a response but a residual disease of approximately 1.5 centimeters of residual invasive carcinoma. We went on to treat her in the adjuvant setting with T-DM1 [trastuzumab emtansine] plus an aromatase inhibitor [AI] and she did well in the adjuvant setting. She completed her 1 year of T-DM1. Unfortunately, 2 years into her AI, she developed a persistent cough, which subsequently initiated an investigation including imaging. And there we found multiple pulmonary nodules, multiple osseous, metastases, and 3 hepatic lesions that were all radiographically consistent with metastatic disease. This was followed up with a biopsy of 1 of her liver masses and we did confirm metastatic carcinoma. The receptor status remained triple positive. We did do an MRI of the brain at that time for screening purposes and the MRI brain was unremarkable. In 2019, she developed metastatic disease so we treated her in the first-line setting with the classic CLEOPATRA regimen, THP [docetaxel, trastuzumab, and pertuzumab]. At Memorial [Memorial Sloan Kettering Cancer Center, New York, NY], we typically use paclitaxel weekly instead of docetaxel and she did very well on this regimen. She had a partial response after 12 cycles of Taxol. At that time, we stopped the Taxol, and this is essentially 3 months into her treatment. We continued Herceptin and pertuzumab in the maintenance setting. I also added fulvestrant [Faslodex] at this time as a reminder she progressed on an aromatase inhibitor. We added some hormone therapy with assert at this point. I think we can pause there to briefly talk a little bit about how we use maintenance therapy in our patients with triple-positive cancers. I think that this is also an exciting space for investigation. My practice is generally to incorporate hormone therapy with antibody therapy at this time. We’re also seeing clinical trials that are testing novel approaches like the addition of CDK4/6 inhibitors in this setting as well as other agents in this setting. But for now, apart from a clinical trial, I do typically incorporate hormone therapy. Milana, do you take a different approach or is this something that you’re also doing in your patients with triple-positive disease?

Milana Dolezal, MD, MSci: Yes. So I think what’s a little challenging in terms of the triple-positive disease and I know that we’re not in the second- or third-line setting yet per se. When you go back and look at the HER2CLIMB study and you look at the subset analyses in terms of those triple-positive or ER [estrogen receptor] and/or PR [progesterone receptor]and HER2-positive patients. You can see that the confidence intervals are wider and part of that, when you think about it, is these patients that were double or triple positive were not allowed to be on anti-estrogen therapy during their chemotherapy. In HER2CLIMB, essentially those patients continued all of those agents, until progression. I just want to point out this is a bit of a dilemma in terms of what to do with hormone receptor-positive and HER2-positive patients because clearly, your patient has a metastatic disease but she also has bone mets [metastasis]. You biopsy the liver lesion that was still triple positive but you wonder well, what’s driving what because we do still see a lot of heterogeneity in terms of HER2 expression and what’s going where. And certainly, he did the right thing in terms of…I always encourage biopsies certainly at any metastatic first-line setting. Don’t just assume that it’s still HER2 positive or triple positive, so I think that’s one point. I think it is also important sometimes to re-biopsy and there are a lot of advances in terms of next-generation sequencing. We have a lot of blood opportunities with Guardant [360] or FoundationOne as well. For some of those bone-only patients, if they have tumor shed to be able to pick up circulating tumor DNA for mutation testing. There are PI3 [phosphoinositide 3]kinase inhibitors available as well so there are other strategies. I think that now if she presented, we would probably put her on with residual disease on one of the compass trials in terms of incorporating T-DM1 plus, minus tucatinib in the adjuvant setting. Of course, the KATHERINE data established T-DM1 in the adjuvant setting after neoadjuvant therapy for patients who didn’t have a pathologic complete response. Unfortunately, then this patient progressed in the maintenance setting, and you appropriately continued to have her on dual therapy including fossil decks as well. I think the challenge is well what are we going to do with patients who are still on chemotherapy and how do we throw the anti-estrogen agents into the mix? Certainly, when they are on breaks from chemotherapy, but I think that’s an evolving space.

Neil Iyengar, MD: Absolutely. I think that the crosstalk between the HER pathway and the estrogen receptor pathway is an exciting area for combining some of the therapies that you just mentioned. Particularly some of the novel molecular therapies like PI3 kinase inhibitors and AKT [protein kinase B] inhibitors and so forth. I do think we’re going to see some data in this space that may influence our practice.

Milana Dolezal, MD, MSci: Just to comment, there’s also the SUMMIT trial and that’s looking more at HER2 mutations but that is in combination so that’s neratinib [Nerlynx], not tucatinib [Tukysa], with fossil deck. I think that’s another translational area that we can look at data from both including adverse event profiles.

Transcript edited for clarity.

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