Although HER2 and hormone therapy approaches are ineffective for patients with triple-negative breast cancer (TNBC), using immunotherapy in those with positive PD-L1 expression has been shown to improve on standard chemotherapy. In a virtual Case-Based Roundtable event for oncologists in Tennessee, moderator Sara Nunnery, MD, MSCI, and participants discussed how they select chemotherapy to use with pembrolizumab (Keytruda) in this setting. Additionally, Nunnery, who is
director of breast cancer research at Tennessee Oncology, presented data on the efficacy and safety of sacituzumab govitecan (Trodelvy) instead of standard chemotherapy in this setting and received feedback on the potential role of this new regimen.
CASE SUMMARY
- A 34-year-old woman presented with a palpable breast mass and mild back pain.
- Biopsy of the breast mass:
- Poorly differentiated invasive ductal carcinoma
- Estrogen receptor expression 0, progesterone receptor expression 0, HER2 expression 0
- Staging PET scan: fludeoxyglucose-avid lesions in bone, lung, and mediastinal nodes
- Laboratory findings: within normal limits, except for moderately elevated alkaline phosphatase
- Biopsy of the lung: confirmed metastatic disease
- PD-L1 testing: combined positive score of 20 using immunohistochemistry 22C3 pharmDx
- Germline testing: negative for BRCA pathogenic variant
DISCUSSION QUESTIONS
- What are the treatment options?
- What do you recommend as first-line therapy?
- What factors influence your recommendation?
- How do you select the chemotherapy partner to use with pembrolizumab?
Sara Nunnery, MD, MSCI: What are the treatment options and what do you recommend as first-line therapy? What factors influence your recommendation? How do you select your chemotherapy partner to use with pembrolizumab? Anybody want to share your approach to that?
Wei Lin, MD: Because the treatment will be until progression or intolerance, and pembrolizumab is given every 3 weeks typically, [I consider that] nab-paclitaxel [Abraxane] has good activity. Instead of giving a 5- or 6-hour infusions like paclitaxel every 3 weeks, I think that this is more convenient and does not occupy too much chair time, even every 3 weeks.
Nunnery: Yes, great points. What about gemcitabine/carboplatin? Some of us probably use both [regimens], depending on the scenario. Does anyone use both? [Can you] share how they how you decide between different partners?
Revathi Kollipara, MD: I feel like I would do gemcitabine/carboplatin if their disease is BRCA positive, but I’ve found that a lot of times gemcitabine/carboplatin [causes] a lot of cytopenias, and I’ve had delayed treatment. So if the disease is BRCA negative, I would probably use a single-agent chemotherapy.
Ibrahim N. Nakhoul, MD: I also think about the long-term adverse events [AEs]. With taxanes, for example, I worry about neuropathy if we’re starting early on that with paclitaxel. That could result into long-term neuropathy in this young patient. So I also take that into consideration.
David Chism, MD: For pairing it with the immunotherapy, I would prefer just 1 chemotherapy rather than [gemcitabine/carboplatin], precisely because of cytopenia related to carboplatin and the long duration of treatment, so I think nab-paclitaxel is probably going to be more favored in this situation.
Nunnery: Does anybody think about doing gemcitabine/carboplatin, for example if you’re concerned about high disease burden, rapid progression, or visceral crisis? Does that sway your decision in any way?
Chism: Not particularly from my standpoint. [Maybe for] liver involvement, but with taxanes and chemotherapy, we use single agents for visceral disease. I don’t know if there are any data to show if they add more, organ-specific data to say, this chemotherapy is going to be favored,
Lin: Gemcitabine/carboplatin [causes] bone marrow suppression, and you are going to deal with more cytopenia. Often we have to skip day 8, and then the dose reduction in a way, so you cannot really achieve what you hope to in terms of efficacy,
Michael Hemphill, MD: I’m a fan of that. With nab-paclitaxel and taxanes, they end up getting neuropathy early. Sometimes it can be irreversible, and you’re [limiting use of] other regimens later. [With gemcitabine/carboplatin], you have to make some dose reductions and dose delays with the cytopenias, but I found that pretty manageable. I like pembrolizumab plus gemcitabine/carboplatin, even though it’s doublet chemotherapy with a low threshold for a drop to 80% dosing. The dosing is going to be whatever the first scan shows. If you already have a response and they’re tolerating it well, then you’re on the right track.
Nunnery: Those are good points. Dr Chism was mentioning liver involvement. We’ve done some gemcitabine/carboplatin inpatient before for young patients with elevated liver function tests and visceral crisis. It can be helpful in that situation. Do you find that the addition of pembrolizumab to the chemotherapy for these PD-L1–positive patients is still well tolerated? Or are you having to deal with more immune-related AEs?
Hemphill: I don’t feel like it adds any incremental toxicity. I remember the first KEYNOTE trial in lung cancer, and I was very skeptical when the addition of immunotherapy didn’t seem to change grade 3 or 4 AEs over a decade ago. Now, anecdotally, I feel like it’s been pretty true. The thyroid is a pain for sure. But outside of…making adjustments [for endocrine toxicity]…I don’t feel like I’ve seen a lot of additional toxicity with it.
Nakhoul: Same here. Now we are used to these drugs, and we use them in all types of cancer. [There are] no major AEs that are not manageable.
Nunnery: Anyone want to share any feelings on current unmet needs still for these patients that are PD-L1 positive in the first line setting. Very leading question for the data we’re going to talk about. Also, what proportion of patients do you do you personally think go on to second line therapy or beyond, just in your practice?
Hemphill: I think the vast majority goes to the second line; 80% would be low, probably closer to 85%.
Nunnery: That’s great, I agree.
DISCUSSION QUESTIONS
- What are your reactions to the ASCENT-04 clinical trial (NCT05382286) data?
- Do you consider them practice changing? If not, what more would you need to see?
- What do you view as the pros and cons of using conventional chemotherapy vs sacituzumab in combination with pembrolizumab for metastatic TNBC?
- For what types of patients would you opt for one over the other?
Lin: I think the data are quite impressive, and the fact that there are not a lot of differences in toxicity on both sides [makes this] something I’ll consider my practice for sure.1
Nakhoul: The data are very interesting. I want to know more about the prior exposure to pembrolizumab. That’s something that I need to know more about, because now we use a lot of neoadjuvant pembrolizumab. The data were probably not mature by then, because we did not use that much before. Would prior exposure to pembrolizumab have any effect positively or negatively on the response?
Chism: I would certainly want to follow the overall survival data. It’s really promising, but it will introduce a new question of how to sequence afterwards. If you’re using [sacituzumab] in that second line, what will we do? How will they respond to the other chemotherapies [later]? But I think it is potentially practice changing. I’d just follow the overall survival.
Nunnery: Those are great points, and I share the same questions with you all. This was conducted before we were routinely using pembrolizumab, and a lot of the countries in this trial did not necessarily have access to the neoadjuvant regimen. It raises the question about patients who got the KEYNOTE-522 [NCT03036488] regimen. Are they going to have the same response rates as this? This may be an opportunity to pool some real-world data going forward.
Does anyone have concerns about diarrhea with the sacituzumab plus pembrolizumab, or concerns about managing that, or teasing out what it could be from? Do we feel like the timing can really be helpful for us?
Hemphill: That was my biggest concern. Each of those independently can cause diarrhea, so you have to try and tease out. How close are we getting to an immunotherapy-induced colitis? I would have a low threshold for steroids, even though it’s probably more likely to be the sacituzumab. [I would give] antidiarrheals, do at least 1 screen for Clostridioides difficile, and give IV fluids as needed. They’re a bit of a captive audience, because they’re coming every few weeks anyway, as well, so that part is not a huge concern, other than the fact that overlaps with a possible life-threatening immunotherapy-induced colitis.
Nunnery: Yes, I feel the same way. I will use antidiarrheals and if it doesn’t respond quickly, use steroids. Better safe than sorry.
DISCLOSURES: There were no known relevant disclosures.
REFERENCE
1. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan (SG) + pembrolizumab (pembro) vs chemotherapy (chemo) + pembro in previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC): Primary results from the randomized phase 3 ASCENT-04/KEYNOTE-D19 study. J Clin Oncol. 2025;43(suppl 17):LBA109. doi:10.1200/JCO.2025.43.17_suppl.LBA109