Clinical Scenario: mTNBC Treated With Chemotherapy Then Sacituzumab Govitecan

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Sara A. Hurvitz, MD:Perhaps we will turn now to a case, and I'm going to pick your brain. How you would manage this particular scenario. So, we have a 57-year-old woman who was diagnosed with stage llA grade 3 triple negative breast cancer. She previously received neoadjuvant docetaxel cyclophosphamide and underwent a mastectomy followed by olaparib because she has a germline BRCA1 mutation. Her tumor was tested and was PD-L1 negative. This treatment was given prior to the availability of neoadjuvant pembrolizumab, and I think that the PD-L1 testing in this setting was investigational, not something that is used to make treatment decisions. But at her 12-month follow-up, she developed a persistent cough and was complaining of right upper quadrant pain. She underwent CT imaging that revealed 2 lesions in the left lobe of the lung, 2 centimeters as well as a single 0.8-centimeter hepatic lesion that was suspicious. She had a biopsy and this confirmed metastatic triple-negative breast cancer. She underwent brain imaging and that was negative for brain metastasis. So, before I actually take us on this journey and talk about her treatment course, can you take me through how you would approach selection of treatment for this patient from a cytotoxic chemotherapy standpoint? What systemic therapy would you put this patient on?

Gregory Vidal, MD, PhD: So, that's a very interesting case and as you said before, PD-L1 testing, at least earlier on, is really just investigational. For this patient, what we do know that accrued in the first-line setting is a PD-L1-based regiment, which is pembrolizumab with chemotherapy if PD-L1 positive, which I would k repeat in this patient on the metastatic lesion so we can have PD-L1 changes occurring from the primary to the metastatic. If not positive, then we do have chemotherapy options, including platinum or taxane. She had 12 months, I think, disease-free interval at least, so which made a taxane available for her. Interestingly, if she had early progression within the 12 months on a taxane- type chemotherapy, I would consider bringing up sacituzumab in that setting; I've done that in a few patients. But, overall, any type of chemotherapy is an option in the first line. GemCarbo [gemcitabine and carboplatin], for example, is another combination option for this patient depending on her tumor burden. Obviously, if you're looking for a response, you might consider doublet therapy versus single agent, but for most patients, single-agent chemotherapy is what would be expected unless they're PD-L1-positive, at which you would give them pembrolizumab. I like to do a molecular profile for my first-line patients, especially the triple negative, so we can recognize the BRCA in a patient, for example. That patient should have been tested up in the earliest setting, even though she's triple negative. Oh, we did recognize that she's BRCA positive. But she's already had olaparib, so I guess that's not an option for her at the first line because it progressed after that therapy.

Sara A. Hurvitz, MD:Thank you very much for that great review. I completely agree with you and I want to highlight 1 thing that you brought up regarding PD-L1 testing. It is so interesting, when you look at data that was generated by Hope Rugo, [MD, FASCO, professor and director of Breast Oncology and Clinical Trials Education, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco] in the context of some clinical trials; she did show that PD-L1 expression levels differ not only from primary to metastatic lesions but also site of tissue. Liver lesions and liver biopsies tend to have the lowest PD-L1 expression, whereas lung and lymph node have really high expression, so I think it's a very salient point that you made to retest and make sure the patient is for sure PD-L1-negative before omitting pembrolizumab, given the significant benefits of pembrolizumab in that frontline setting. As it turns out, this particular patient did start on cisplatin. She received 3 cycles of therapy and experienced disease progression. One of her lung lesions increased to 2.7 centimeters and the liver lesion increased to 0.9 centimeters; therefore, it was a true progression. One thing I would highlight, as you mentioned, is she received olaparib in the adjuvant setting, and we don't have really good data about the efficacy of platinum drugs in BRCA carriers after a PARP inhibitor. We know that a PARP inhibitor after progression on a platinum doesn't appear to work as well, but there does seem to be some level of cross resistance, so I can't say that this lack of response that we saw is something unusual. I think you mentioned that your next choice in the second line setting would be sacituzumab govitecan, so I wanted to get your input regarding sacituzumab govitecan and what type of responses you've seen in the metastatic setting and your patients whom you've treated with this agent.

Gregory Vidal, MD, PhD: We know the data from ASCENT trial [NCT02574455] showed there is almost a doubling of progression—actually from 1.7 to 5.6—more than a doubling of progression free survival. It was overall survival benefit. In the real world, with my patients, I've had patients who've been on this drug for probably the longesgt 18 months I think and doing well. They have really good dip responses before having progression. Also, I've had some patients who have had really short intervals of benefit, but overall, most patients that I've given the drug do pretty well--At least get some response over time, somewhat in line with what we've seen in the trial. Right about maybe 5 to 6 months’ benefit.

Sara A. Hurvitz, MD:Yes, I've noticed some really nice outcomes with my patients as well in terms of treatment with sacituzumab with very robust responses, even in patients with liver metastases. I've been very pleased with the type of activity that I've seen, and certainly, as you mentioned in the ASCENT study, it underscores the improvement and objective responses and clinical benefit rate. We have to keep in mind patients were really heavily pretreated in the ASCENT trial. So, perhaps by using it in a little earlier setting, in the second- or third-line setting, we might see even better activity.

Transcript edited for clarity.