Part 2: Managing Toxicities of Sacituzumab Govitecan in Metastatic TNBC

Rita Nanda, MD (Moderator)

Director, Breast Oncology

Associate Professor of Medicine

University of Chicago

Chicago, IL

CASE SUMMARY:

A 48-year-old woman with T1N1 triple-negative breast cancer (TNBC) received adjuvant 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.​

The patient received frontline gemcitabine plus carboplatin with a documented partial response lasting 6 months​. After 6 months of therapy, she reported worsening fatigue. Disease progression and new metastasis in the liver was discovered. ​She now had an ECOG performance status of 1​.

DISCUSSION QUESTIONS:

• Have you had personal experience with sacituzumab govitecan (Trodelvy)?​
• Please discuss your experiences with sacituzumab govitecan​ in terms of efficacy, tolerability. What is your approach to monitoring and management?​
• How do you counsel your patients regarding sacituzumab govitecan?​

NANDA: For those of you who have used sacituzumab, do you want to share your thoughts regarding how effective you’ve seen it be in your practice, and the issues around tolerability and toxicity? I know it hasn’t been out there all that long.

NEEL SHAH, MD: I’ve had a couple of patients on it and thus far, they’re responding well and tolerating the drug very well. I haven’t had any severe toxicities.

NANDA: Does anyone else have any experiences with toxicities that they’re concerned about or any particular patients that had a response or not had a response?

ROBERTO MONTOYA BARRAZA, MD: I had 2 patients. Both had diarrhea. One needed a dose reduction. And then eventually, she had a response. The other one couldn’t tolerate the drug—severe diarrhea, severe nausea, and vomiting. However, I have to say that this patient was unable to tolerate any other kind of drugs. In both, what I have seen is diarrhea and nausea. It could be difficult to manage that part.

NANDA: How did you manage diarrhea for the patient?

BARRAZA: Well, we had to discontinue this drug for 1 patient. She refused to continue it. The other 1 had some dose reduction, Imodium [loperamide], and Lomotil [Diphenoxylate / Atropine]. And eventually, she became able to tolerate it.

KOZLOFF: I had 1 patient with diarrhea and they rapidly progressed on it. We did reduce the dose and give loperamide for diarrhea which controlled it, but they did not have a response.

FLEJSIEROWICZ: I haven’t had good luck yet either. My patient could not tolerate it. It was diarrhea mainly. But with those in dialysis, nausea is always there. It’s too early to tell whether it improved anything or not. They’re not doing well, but it could be for the same reason that she had difficulty with other drugs before. I will see how it goes.

DISCUSSION QUESTIONS:

• What are you using most often as next-line therapy for progression on/after sacituzumab govitecan? ​
• If you aren’t using sacituzumab govitecan in the second line, what are you using and why? ​

NANDA: What are you using after patients progress on sacituzumab? And have you had much luck with any therapies in that space? This patient had carboplatin/gemcitabine and now sacituzumab. What would you offer as that next line of therapy?

GOWRI RAMADAS, MD: At what point do you rebiopsy?

NANDA: That’s a good question. I don’t generally rebiopsy them constantly. Do you mean to do next-generation sequencing to look for something new?

RAMADAS: Yes.

NANDA: The biomarkers wouldn’t necessarily change if it’s already TNBC. It’s not unreasonable [to test]. I don’t generally continue to rebiopsy a patient at every disease progression unless it’s required by a trial. Because I would argue that what’s driving the cancer is likely there from the start. And unless you’ve had selective pressure selecting against that, I doubt that what you see subsequently is going to change dramatically, that you’re going to have some major new finding that’s going to be targetable that is going to change outcomes for patients. It’s not unreasonable to rebiopsy at least once, but I generally don’t continue to rebiopsy.

KOKO: I think it would probably be the time to check for high microsatellite instability (MSI) to see if she would be a candidate for immunotherapy.

NANDA: You wouldn’t do that from the start? I generally do that on my initial assessment. I don’t know that MSI is going to change over time.

For those of you who aren’t using sacituzumab in the second line, is there a reason you wouldn’t consider it when we’re seeing the survival advantage here? Or is that some new information that might change your mind? It seems like most of you were using it in the second line.

KOKO: If the disease recurred in this patient 24 months post initial treatment and she’s had gemcitabine/carboplatin, and then she moved on to sacituzumab, would you want to revisit taxane?

NANDA: That’s not an unreasonable thought. A lot of times, for my patients who recur after 12 months, I do consider retreating with a taxane. I think that’s a very perfectly reasonable option for this patient….I don’t know that I have had success with anything after sacituzumab.