During a Targeted Oncology™ Case-Based Roundtable™ event, Hope S. Rugo, MD, discussed with participants the management of neutropenia and other toxicities associated with the antibody-drug conjugate sacituzumab govitecan in patients with metastatic triple-negative breast cancer.
A 48-year-old woman with T2N+ triple-negative breast cancer (TNBC) received neoadjuvant dose-dense doxorubicin and cyclophosphamide with paclitaxel, which she tolerated well. She underwent lumpectomy with axillary lymph node dissection. There was 1-cm residual disease in the breast and no residual disease in axillary lymph nodes. She received adjuvant capecitabine (Xeloda) for 6 cycles. Eight months after completion of adjuvant therapy, she reports worsening fatigue.
Laboratory results showed alanine transaminase was 1.5x upper limit of normal (ULN), and aspartate aminotransferase was 1.5x ULN. ACT scan showed 3 liver and 2 left lung lesions. A biopsy of the liver lesion confirms recurrent metastatic TNBC. Brain MRI was negative for brain metastasis.
Genetic panel testing was negative for detectable mutations. PD-L1 by immunohistochemistry 22C3 pharmDx showed a composite positive score of 0. She had no significant comorbidities and was otherwise healthy, with an ECOG performance score of 0.
DAVID KAHN, MD: I haven’t used this drug.
HOPE S. RUGO, MD: Is that because you don’t see a lot of breast cancer?
KAHN: I don’t.
JASPREET CHAHAL, MD: I just haven’t had the right patient come along yet to use it for.
RUGO: That’s a lucky thing though because these patients with metastatic TNBC are tough especially because, at least in my clinic, they’re mostly young and they get early brain metastases.
PRANSU BANSAL, MD: Most of my experience with sacituzumab has been with bladder cancer…. But I’ve had a couple of patients with metastatic TNBC. Neutropenia and alopecia have been the biggest concerns for me, especially with patients with bladder cancer. The way I manage neutropenia is dose reduction in the metastatic setting and add pegfilgrastim [Neulasta] support if even after 1 or 2 dose reductions they still are neutropenic. One patient also developed a pretty significant rash, so he responded to topical steroids and slight dose reduction.
RUGO: That’s interesting. We haven’t seen much rash but anything can happen.
BANSAL: This rash was mostly on his scalp and his face but that was only 1 patient on the trial.
RUGO: When those things happen, [it depends on] whether they’ve had immunotherapy before and this was some sort of immune flare. We’ve seen that before; these late flares with giving another chemotherapy drug.
If the patients needed growth factors for their last treatment, are you likely to give it with sacituzumab up front or do you wait for them to become neutropenic?
BANSAL: I’ve had insurance issues for getting it up front, so I have had a couple of patients denied for primary prophylaxis. I would like to, because I think the degree of neutropenia is pretty high in people who have previously been neutropenic and previously had chemotherapy, especially if you’re starting at the full dose. But I’ve just not had good luck with insurance.
RUGO: You could always have your clinic send the National Comprehensive Cancer Network [NCCN] guidelines for growth factor use because [due to] the rate of grade 3 and 4 neutropenia, along with the rate of diarrhea, [it] would be approved.1 At least it’s in the NCCN guidelines that in those patients you could use prophylaxis up front.
BANSAL: That’s good to know.
RUGO: One of the things that’s important to me is if patients have any evidence of mucosal toxicity, that it’s even more important to be preventing or treating neutropenia early because you can get typhlitis or bacteria that cross the bowel or even perforation if you’re neutropenic and you’re having some diarrhea or gastrointestinal toxicity.2 So I think it’s even more important then, because the neutrophils protect the mucosal barrier so much.
ELISA BOMGAARS, MD: Do you normally check for UGT1A1? Do you normally do that on your patients when you start them?
RUGO: We published the data on UGT1A1 and the *28 homozygous group did have more neutropenia but not more diarrhea.3 But because neutropenia is already so common, we don’t recommend and the FDA didn’t recommend adding testing. If you’re at the Mayo Clinic and it’s next door, it’s easy to do. But in our situation, where in the time [it takes] for it to come back I would have already given my first cycle, we don’t check because I use patients’ neutropenia with their previous treatment as a reason to give growth factor or not. If I’m treating even the first line, which I have done, then I won’t give growth factor up front because I found that patients don’t need it right away. But, if somebody was getting gemcitabine/carboplatin and already was neutropenic with growth factors, I’ll use it up front rather than checking the UGT1A1. We just published those data in NPJ Breast Cancer. Is anybody testing UGT1A1?
RITA MAITY MUKHERJEE, MD: No, I don’t test.
CHRISTOPHER CHEN, MD: I do it in a reaction setting. If a patient has horrible neutropenia, then I might consider it. But otherwise if they tolerate it OK, I manage accordingly.
RUGO: Do you ever use long-acting growth factors? I saw a patient recently who was getting pegfilgrastim after day 8 and that’s all that she received.
CHEN: Most of my growth factors I tend to use are short-acting ones just because of limitations of our practice patterns.
RUGO: So you’ll give short-acting growth factors once or twice and dose reduce?
CHEN: Correct, if necessary.
RUGO: I had one patient on 3 doses after each infusion, but she’s 82 and she got the dose every other week. She stayed on for 8 months, but I think often older women have less bone marrow reserve so it’s a bigger issue. Is anybody else using long-acting growth factors?
DARSHIL SHAH, MD: I’ve used long-acting growth factors. I think after day 8 it makes sense, but we need to have at least a 2-week period between the next chemotherapy.
1. NCCN. Clinical Practice Guidelines in Oncology. Hematopoietic growth factors, version 1.2023. Accessed February 20, 2023. https://bit.ly/417X5sX
2. Trodelvy. Prescribing information. Immunomedics, Inc; 2020. Accessed February 20, 2023. https://bit.ly/3lRzcW9
3. Rugo HS, Tolaney SM, Loirat D, et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. NPJ Breast Cancer. 2022;8(1):98. doi:10.1038/s41523-022-00467-1