Part 1: Choosing Therapy for a Patient With Recurrent 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.

DISCUSSION QUESTION:

• If you chose chemotherapy or other, what agent/regimen are you most likely to recommend?

RITA NANDA, MD: What therapy would you offer this younger woman with metastatic TNBC, who presents with recurrent disease 8 months after completing adjuvant therapy? It looks like a pretty even split between intravenous [IV] single-agent chemotherapy or offering the patient a clinical trial, and one vote each for oral chemotherapy or other.

For the person who voted for other, could you comment on what you might recommend for that patient?

RAMI HADDAD, MD: I was thinking of any immunotherapy, if eligible.

NANDA: Would you offer immunotherapy to someone who had PD­-L1-negative TNBC?

HADDAD: I wouldn’t, but it’s a consideration.

NANDA: What single-agent chemotherapy would most of you offer the patient? What are typical strategies that you might use?

ISOKEN KOKO, MD: Single-agent carboplatin [is an option].

NANDA: Would anyone else consider that for their patients? Would anyone offer doublet therapy? I don’t know if that was an option for anyone.

HADDAD: With visceral disease and a high burden of disease, carboplatin/gemcitabine would be a choice I would lean towards.

RONALD SHADE, MD: I agree. I think platinum-based chemotherapy is a good selection and I would prefer gemcitabine/carboplatin.

NANDA: I use that a fair bit in my practice as well. What clinical trials are you offering to these patients? What’s interesting out there that you all have in your practices that would be reasonable to offer? Just referring to a trial or treating in-house? I don’t know if anyone has something interesting that they’re excited about in this space.

SHADE: I think there are some PARP inhibitor trials out there.

HADDAD: In part of the US Oncology Network, we have some novel immunotherapies in the basket of diseases including TNBC. But given the lack of phase 2 studies with higher numbers, I would not do it in the first line.

KOKO: I would think of genomic testing for this patient to see if the patient is microsatellite instability-high or if it’s BRCA somatic mutation-positive.

NANDA: I think those are certainly reasonable options. Would anyone else do next-generation sequencing [NGS] on the tumors as well? I believe this patient had germline testing which was negative. But I agree. There was no comment made about NGS.

MARK KOZLOFF, MD: I would use germline testing because I send my patients to the University of Chicago Medicine. There’s a 15% chance of a certain abnormality and they have a study for it. I would check for that.

DISCUSSION QUESTIONS:

• Would your frontline approach differ if relapse occurred 24 months after adjuvant therapy?​
• If you chose chemotherapy or other, what agent/regimen are you most likely to recommend?​

NANDA: This is a slightly different take on the same patient. Again, a 48-year-old woman with metastatic TNBC. BRCA1- and BRCA2-negative, PD-L1-negative. But her disease recurs 2 years after the completion of adjuvant therapy.

How would that change your approach here? It sounds like more people would be willing to use oral capecitabine in this setting.

Interestingly, the patient prior to this would probably be less likely to be eligible for some of those frontline trials given that short disease-free interval. Most of these frontline trials require a disease-free interval of 12 months, and this patient might fit into that category. It was interesting to see that there were fewer people who would want to offer this patient a trial, but perhaps because there’s a suggestion that there’s some chemosensitivity given that 2-year disease-free interval, and a greater willingness to try oral capecitabine.

Does anybody have anything to add? What made you change from a clinical trial or IV single agents to oral chemotherapy?

MAGDALENA FLEJSIEROWICZ, MD: I don’t know if [my approach] changed, but the fact that she [responded] at first is telling me that she may have a little bit more indolent disease in spite of the visceral sites. I may get some years from single-agent paclitaxel or a month to a couple of years. I’ve had it happen to my patients. It’s well-tolerated outside of neuropathy, which can be telling me to stop.

NANDA: What would you have offered the version of this patient with earlier relapse?

FLEJSIEROWICZ: The question would be if she is eligible [for clinical trials]. It’s not that I had a particular study in mind, but I would screen [her] and make sure I don’t miss a window of enrolling her in some studies. I’m surprised by what you just said, but it’s interesting not to miss anything or not to pretreat heavily. Then the performance status would not be good enough for a clinical trial. Screen first and then offer treatment.

NANDA: That’s a great point. I agree with you. It’s frustrating that a lot of these frontline trials require a 12-month disease-free interval. Because when you think of clinical trials, it’s those early relapses that you worry the most about and want to offer novel therapy to. I share that thought process with you.

I will say we do have a trial right now of sacituzumab govitecan [Trodelvy] with or without pembrolizumab [Keytruda] in early relapses who are PD-L1 negative. There are some trials out there, looking at these early relapses. But most trials have historically required a disease-free interval of a year.