Exploring Sacituzumab Govitecan and Other Second-Line TNBC Therapies

Elizabeth Ann Mittendorf, MD, PhD

Robert and Karen Hale Distinguished Chair in Surgical Oncology

Associate Chair for Research, Department of Surgery

Brigham and Women's Hospital

Director, Breast Immuno-Oncology Program

Codirector, Breast Cancer Clinical Research Program

Dana-Farber Brigham Cancer Center

Boston, MA

CASE SUMMARY

A 48-year-old woman with T1N1 triple-negative breast cancer (TNBC) received adjuvant dose-dense doxorubicin plus cyclophosphamide with paclitaxel (ddAC-paclitaxel), which she tolerated well. Eight months after completion of adjuvant therapy, she reported worsening fatigue. ​Laboratory results showed 1.5 times elevated levels of alanine transaminase and aspartate transaminase above the upper limit of normal, and a CT scan showed 1 liver lesion and 2 left lung lesions. A biopsy of the liver lesion confirmed recurrent metastatic TNBC. A brain MRI was negative for brain metastases.

Genetic panel testing was negative for all detectable mutations. PD-L1 expression on immune cells was 0%. The patient was otherwise healthy with no significant comorbidities and had an ECOG performance score of 0.

Following recurrence at 8 months from treatment, the patient received first-line gemcitabine plus carboplatin with a documented partial response lasting 6 months​. After 6 months of therapy, she reportd worsening fatigue. Imaging revealed disease progression in the liver with new and enlarging metastases​. Her ECOG performance score is now 1.

DISCUSSION QUESTIONS

• Which therapeutic option would you seriously consider? ​
• If you chose chemotherapy or other in the polling question, what agent/regimen are you most likely to recommend? ​

SETH WANDER, MD: I was thinking about doublet chemotherapy. I think more about the degree of transaminitis and thinking about whether we need to debulk faster.

But it sounded like her symptom burden was minimal, and the degree of elevation was mild. I don’t think it’s wrong to give this person a single agent and escalate if needed if you’re not seeing control pretty quickly.

A practical question that often comes up is if you’re going to give a single agent is how [closely] do you want to follow the patient? We have weekly regimens versus some that are every 2, or 3, or 4 weeks. In a patient like this, if I was going to give a weekly regimen, or if I was going to give a single agent, I’d want to watch her closer. You don’t want her cut loose for 3 weeks at a time if you don’t know what direction her liver dysfunction’s going to go. So, maybe this is a good person, if you’re going to get a single agent, to give weekly paclitaxel, vinorelbine [Navelbine], or something like that.

ELIZABETH ANN MITTENDORF, MD: Yes, I think there might be a little pushback for weekly paclitaxel if she’s recurred within 8 months of getting her adjuvant paclitaxel.

WANDER: I mean some weekly agent where you’re going to be seeing her laboratory results with some degree of regularity as opposed to a patient who’s doing really well, who has minimal disease, whose laboratory results look good, [or] who has maybe radiographic progression. Something that’s every 3 or every 4 weeks, from a quality-of-life [perspective], may be more appealing in that scenario.

MITTENDORF: Yes, I agree. Does anybody else want to give some general thoughts about how they approach these patients with an early recurrence?

ANKUR MEHTA, MD: I had picked carboplatin/gemcitabine in this scenario, even though it was a doublet. But [I favor] the idea of bringing a platinum agent; it’s a different agent. I’m not a big fan of capecitabine in TNBC, unless it was about an [issue with] the toxicity profile or the idea of taking it orally. I think I would jump on to sacituzumab govitecan [Trodelvy] after carboplatin/gemcitabine.

DISCUSSION QUESTIONS

• Please discuss your experiences with sacituzumab govitecan​ including toxicity and management.

PAUL UNGER, MD: I had a patient that I inherited from another provider who received neoadjuvant ddAC-paclitaxel, and progressed through that. I was able to get sacituzumab approved for her; I was able to convince the insurance company that because she progressed through both doxorubicin and then a taxane, that was essentially 2 regimens for metastatic disease. She went on sacituzumab and did extremely well for about a year. So, I was incredibly impressed with it as my first time out, notwithstanding some of the issues in terms of the alopecia. She was…responding to something in a situation where we have seen other patients like this crash and burn fairly quickly in that setting.

SHEILA DONNELLY, MD: I have a patient on it that has been doing very well for over a year. She interacts with other women who are on the drug, she’s aware of how other patients are doing, and she is clearly among the better ones. As long as it works, I think it’s very well tolerated. The diarrhea can be easily managed, in this case, with diet. I am pleased to have this, and I’ll be interested to see if this has applications in the estrogen receptor–positive population, where there are studies going on right now.

WANDER: It’s been generally well tolerated. We’ve definitely run into problematic challenges with cytopenia more than anything else, particularly in patients that have been heavily pretreated. But with regard to some of the other things that we’ve been talking about, I think it’s been fairly easy to manage.

MITTENDORF: How do you counsel your patients receiving sacituzumab, with respect to adverse events [AEs] that they might experience? Dr Donnelly, it sounds like you are optimistic; what do you tell your patients they might anticipate?

DONNELLY: The diarrhea’s an issue, and my first patient ended up having constipation because of the anti-emetic drugs that she received. Fortunately, it was in the summertime, and I went back to some of the dietary recommendations [such as] using fresh fruits and vegetables from the farm stands, which turned out to [make it] be a lot more palatable than a lot of drugs. So, by using those kinds of things, I think the diarrhea is manageable. Neutropenia can be an issue, but I have not found it to be overwhelming.

DISCUSSION QUESTION

• Please discuss the outcomes of the phase 3 ASCENT trial (NCT02574455) in the context of other therapies that have been most commonly used in the setting of relapsed/refractory mTNBC.​¹

MITTENDORF: [For] the outcomes of the phase 3 ASCENT trial…my first thought was, “Wow, the efficacy of sacituzumab is so much better than chemotherapy.” It is chemotherapy, but [better than] other agents. How do you think this fits in with the game-changing treatments we’ve seen in TNBC over the last couple years?

MEHTA: I find the control arm essentially showing how pathetic the options are for this group and keeping a low bar for sacituzumab to do better. It’s an antibody-drug conjugate [ADC], and hopefully in every cancer we’ll have more ADCs. Although, this one does work like chemotherapy, and the AEs are somewhat like chemotherapy would be: cytopenias and diarrhea. But, in general, I would second everyone’s comments about it being generally well tolerated. We are able to manage and fine-tune these AEs.

But, to the progression-free survival, I’m more impressed by the overall survival [OS], which is significantly better.¹ That OS, as Dr Donnelly mentioned about her patient who has been receiving it for a year, is very reflective of how those who do respond tend to have the durability of response, and that’s what I’m excited about.

_Reference:

_{1. Bardia A, Hurvitz SA, Tolaney SM, et al. Sacituzumab govitecan in metastatic triple-negative breast cancer. N Engl J Med. 2021;384(16):1529-1541. doi:10.1056/NEJMoa2028485}