During a Case-Based Roundtable® event, Stephanie L. Graff, MD, discussed biomarker testing and treatment exposure for a patient with metastatic breast cancer in the second article of a 2-part series.
CASE SUMMARY
Medical/Social History
Initial Diagnostic and Surgical Procedures
Three Years After Completing Letrozole
Follow-Up Diagnostic Tests
First-Line Therapy: CDK4/6 inhibitor + aromatase inhibitor
After 9 Months of Chemotherapy
Follow-Up Diagnostic Tests
Treatment
DISCUSSION QUESTION
STEPHANIE L. GRAFF, MD: Are any of you testing for UGT1A1*28 in your practices right now?
ROBERT HOROWITZ, MD: No, but we've talked about it.
MADHURI YALAMANCHILI, MD: I tested 1 patient after she had a lot of cytopenias, even after 1 dose, because her son requested it. She had heterozygous [genotype], which was surprising. I already gave her dose reductions because she had a hard time through adjuvant therapy, but she still had a hard time. But [I didn’t test] proactively, just at request by the family.
GRAFF: I feel like it should be an easy thing to do. Implementing institutional policies that are simple and easy to follow uniformly is never as easy as it should be. I hope [soon] I'll be able to tell you confidently that we're doing it and we have risk-benefits about this strategy of continuing [therapy] in our zygote carriers moving forward, so more to come.
PAUL S. UNGER, MD: Are there accepted dose reductions or dose differences that you would use based on the testing? Or is it more, if there is something, beware, because we've been around on this with the 5-FU dihydropyrimidine dehydrogenase testing in the past, and you can have an abnormal result in someone who tolerates it fine, and patients who don't tolerate it with a normal result. I understand the mechanism, [but if we] don't know enough about it. If we start testing patients, we might be dose reducing patients who may or may not have a problem.
GRAFF: I don't think that we have the right answer or the prospectively validated answer to your question. My anecdotal thoughts would be that if I found somebody who had it, and [sacituzumab govitecan] was their best treatment option, I would probably start them at a reduced dose. Alternatively, if I found someone who had it and I was trying to decide between numerous potential lines of therapy, it would steer me to make a different choice. One of the luxuries of being a breast oncologist is that we do often have a choice, and so it might be worth knowing. Time will tell.
DISCUSSION QUESTIONS
GRAFF: How are you thinking about lines of chemotherapy? In this patient case, her chemotherapy had been 8 years prior, and that was her docetaxel exposure. How does that timing affect when you're using sacituzumab vs reusing a taxane or a different ADC?
TARA BERMAN, MD, MS: I treat mostly gynecologic malignancies, so for us, our rule of thumb is recurrence 6 months later, then we'll call them platinum sensitive so then we can reintroduce. I don't know if you do the same thing with paclitaxel. I just started treating breast malignancies so I'm here to hear what the consensus is among everyone else, but I am just trying to extrapolate my knowledge from gynecologic oncology.
GRAFF: That's probably accurate for triple-negative breast cancer because the proliferative rate and the cellular biology of the cancer is so much more similar to ovarian cancer in the biologically aggressiveness of the tumor. In hormone-receptor positive disease, I just don't know if that's true. I counted the taxane for this case because I had used docetaxel up front. But single-agent paclitaxel is well tolerated and sometimes it's hard, especially in older patients in whom I’m worried about the adverse event profile, not to use that earlier than some of the ADCs, so it's always a good discussion.
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