POLL: What Treatment Would You Choose for BRCA-, PD-L1- Metastatic TNBC?

CASE SUMMARY

A 48-year-old woman with T1N1 triple-negative breast cancer (TNBC) received adjuvant dose-dense doxorubicin and cyclophosphamide (ddAC) plus paclitaxel, which she tolerated well. Eight months after completion of adjuvant therapy, she reported worsening fatigue. Laboratory results: alanine aminotransferase, 1.5x upper limits of normal (ULN); aspartate aminotransferase, 1.5x ULN. A CT scan showed 1 liver and 2 left lung lesions.Biopsy of the liver lesion confirmed recurrent metastatic TNBC, and her brain MRI was negative for brain metastasis. Genetic panel testing was negative for detectable mutations. PD-L1 on immune cells (SP142 Ventana assay) was 0%. There were no significant comorbidities, otherwise healthy. She had an ECOG performance status of 0.

Vote in the polls below on what you would have chosen if this was your patient.

RESHMA L. MAHTANI, DO: If you chose chemotherapy or other, what agent or regimen are you most likely to recommend?

JANE SKELTON, BSN: I was between a clinical trial and capecitabine but she's going to be difficult to treat chemotherapy wise, so clinical trials reasonable. She has ECOG performance status 0, and I don't know how long she'll stay that way. For that reason, I think for quality-of-life issues, capecitabine would be my choice to give her maybe some time that was reasonable.

LAWRENCE M. NEGRET, MD: I also chose capecitabine. I think all of them are very reasonable choices, but for tolerability and efficacy, I would probably choose capecitabine first line in someone who’s PD-L1 negative.

JAY WANG, MD: If there's any clinical trial available, that would be my preference.

If not, oral capecitabine is probably what I would choose outside the clinical trial setting.

MAHTANI: So let me ask the question, another way, is there anyone who chose I single agent chemotherapy that wants to speak up and just give you a rationale for that route, as opposed to keep sight of being in the situation?

BHANU VISVALINGAM, MD: I chose intravenous [IV] chemotherapy. I would choose sacituzumab govitecan [Trodelvy]. It's a new drug and response rates are really good with that drug as opposed to other single-agent chemotherapy regimens.

MAHTANI: Do you mind telling us what you chose in the first scenario and how you changed your response for this, if you did?

ANDY LIPMAN, MD: I chose clinical trial for both answer. This one and the previous one. To me, the 24 months did not change my thinking. I was confused about the sacituzumab thought because I think it's approved for 2 prior lines of therapy and 1 can be within the adjuvant setting.

MAHTANI: It is approved after [at least] 1 line of therapy for the metastatic setting. If you could get for sacituzumab, it sounds like that's something that you may have been interested in.

LIPMAN: Yes, I agree with the earlier speaker. I have used the therapy in patients with this disease and at this stage, and I agree there have been some really great responses. I have a woman who's 65 years old, presented very similar to the pattern that you had [in this case]; she had earlier-stage disease 2 years ago, adjuvant therapy, late recurrence, and significant amount of disease on the chest wall. Sacituzumab has been relatively well tolerated except for some fatigue a single-agent IV and has healed the skin wound issues well.

MAHTANI: In the situation where a patient recurs after 8 months of treatment in the adjuvant setting, my general thought is we're dealing with a patient who has quite resistant disease. I don't think there's a right or wrong answer in terms of non–clinical trial-based chemotherapy. She seems to be relatively asymptomatic except for mild fatigue. She didn't have a huge burden of visceral disease. I probably would have used capecitabine in that situation.

Then similarly, I think treatment is palliative, even in the 24-month range. Afterwards, she's not symptomatic or overly symptomatic. I don't think there's a right or wrong answer. But capecitabine would be a reasonable approach there as well. If I were going to use IV chemotherapy, I would be more inclined to consider it in the first scenario where the patient had a very short disease-free interval just knowing that that patient isn't likely to do well with her disease recurring so quickly.

CASE UPDATE

The patient received frontline 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. Her ECOG performance status is now 1.

MAHTANI: I want to ask you for your input in terms of how you're making this decision. If you chose chemotherapy or if you chose something other than sacituzumab in the first-line or second-line situation, are you using a different agent? Please address the ideal therapeutic sequence for these patients with triple-negative disease who are PD-L1 negative. This is a considerable population of the patients; we have about 40% of patients that have PD-L1–positive disease but there's a fair percentage of them that are negative, so how are you approaching these situations?

JORGE HURTADO, MD: Usually in patient with PD-L1­–negative disease, it is based on the amount of disease that we're dealing with, what they have received before, and tolerability. Usually, if you have had a lot of disease, starting with [starting with an oral agent is] not a bad idea, especially if the patient is extremely symptomatic. If a patient is doing is relatively OK, doesn't have high burden of disease, I tend to start with single agent, and we can also use Doxil (doxorubicin), which is easy to tolerate. I try to balance what I need to do for the patient to make them feel better and improve the quality of life, what they can tolerate, and what is available.

DIMITRIOS P. AGALIOTIS, MD: If PD-L1 [expression was] negative, I would think mostly of the new medication sacituzumab, and Doxil as my colleague said….I think it is a good path, but it's again, what's available, what the patient wants, considered toxicities, and proceed that way.

MAHTANI: I'm definitely hearing decision making is informed by IV versus oral, shared decision-making, and toxicities that that they may have had in the past. In this scenario of the patient having recurred within 24 months versus 8 months, what you do in the second line? Does that does that recurrence, the timing of the initial recurrence, change how you look at that patient going forward? Or are you following this algorithm that once you start, it really doesn't matter when the patient had a recurrence?

RICARDO D. PARRONDO, MD: If it's the first recurrence—for example, if she would have progressed 8 months after a ddAC—I would go with single-agent carboplatin because it's chemotherapy with different mechanism of action. If they are young and/or fit, I'd like to save the capecitabine for later, keep it in my back pocket in case they become less fit. That's a better tolerated treatment.

If she would have progressed within 24 months initially, we'll go back to single-agent taxane. But then, in the relapse after first line, for second line metastatic disease, I would go with sacituzumab regardless. I like to cycle the chemotherapy with a different mechanism of action.