The answer, published in the journal Supportive Care in Cancer, leans toward restraint. In the retrospective cohort of 303 women treated between August 2021 and April 2025 within the Central European Breast Cancer Collaboration initiative known as CEBCC-102, one hundred patients received primary prophylaxis with granulocyte colony-stimulating factor, or G-CSF, starting from the first cycle of sacituzumab govitecan, while 203 patients began treatment without it. The two groups showed no statistically significant differences in progression-free survival, overall survival, or febrile neutropenia, the feared complication in which fever signals a serious infection during a period of profound immune suppression.

The numbers tell a nuanced story. Median progression-free survival was 4.2 months in the primary prophylaxis group compared with 5.1 months among patients who did not receive upfront growth factor support, a difference that failed to reach statistical significance. Median overall survival was similarly close, at 10.9 versus 11.6 months. Febrile neutropenia struck roughly the same small fraction of patients in both arms, occurring in 4.0 percent of those given primary prophylaxis and 4.4 percent of those managed reactively. Dose reductions of sacituzumab govitecan due to toxicity were also essentially identical, at 36.0 percent and 38.4 percent respectively, suggesting that neither strategy preserved treatment intensity more effectively than the other.

Where the strategies genuinely diverged was in the laboratory. Severe neutropenia, graded as grade 3 or 4 under the standard CTCAE toxicity criteria, was significantly less frequent among patients who received growth factor support from the start, affecting 33.0 percent of that group compared with 50.7 percent of those who did not. That difference, statistically significant at a p-value of 0.005, confirms the biological logic of prophylaxis: stimulating the bone marrow in advance does blunt the depth of chemotherapy-induced myelosuppression. Yet the clinical consequences of that blunting, in terms of fever, infection, dose delays, or survival, simply did not materialize in this cohort, largely because the reactive strategy worked well enough.

That last point is the crux of the study’s most striking observation. Among the 203 patients who began treatment without primary prophylaxis, 74.4 percent subsequently received G-CSF as secondary prophylaxis after experiencing a neutropenic episode. In other words, the reactive approach was not a strategy of neglect; it was a strategy of vigilant monitoring followed by prompt intervention. By the end of treatment, only 52 patients, or 17.2 percent of the entire cohort, had never received growth factor support at all. The authors caution that this high rate of secondary use means the absence of a survival difference should not be read as evidence against G-CSF itself, but rather as a lack of demonstrable advantage for routine upfront administration over timely reactive use.

The regulatory landscape surrounding this question has been shifting in ways that make the new data timely. The National Comprehensive Cancer Network’s Hematopoietic Growth Factors Guidelines classified sacituzumab govitecan as a high-risk regimen for febrile neutropenia, exceeding 20 percent, in Version 1.2026, but reclassified it as intermediate risk, with an estimated febrile neutropenia rate of 10 to 20 percent, in Version 3.2026. For intermediate-risk regimens, guideline logic holds that growth factor use should be guided by individual patient characteristics rather than applied uniformly. The drug’s Summary of Product Characteristics likewise recommends considering primary prophylaxis only in patients at increased risk, including those aged 65 or older, patients with a prior history of neutropenia, poor performance status, organ dysfunction, or multiple comorbidities.

Comparing the Central European cohort with prospective trial data reveals the familiar efficacy-effectiveness gap. In the phase 2 PRIMED trial, which prospectively applied a predefined prophylactic strategy combining G-CSF with loperamide in selected patients with HER2-negative advanced breast cancer, grade 3 or 4 neutropenia occurred in only 16 percent of patients during the first two cycles, well below the rates seen in routine practice. The real-world patients in the CEBCC-102 analysis were treated in the second or later line with greater heterogeneity in prior therapy and supportive care, and their higher neutropenia rates reflect that less selected population. Other real-world studies from the United States, Turkey, the United Kingdom, France, and southern Spain have reported broadly comparable survival figures, with median overall survival hovering around 10 to 11.6 months, reinforcing the external validity of the new findings.

The study also illuminates the economics and logistics of supportive care. Because more than four out of five patients in the cohort ultimately received G-CSF at some point, the analysis suggests a supportive-care-oriented practice style in Central Europe, with relatively liberal growth factor use and comparatively less reliance on dose reduction of the anticancer drug itself. That pattern matters because exposure-response analyses indicate that higher sacituzumab govitecan exposure is associated with a greater probability of response and longer survival, and a Polish real-world study found that initial dose reductions of 20 percent or more were independently linked to shorter progression-free and overall survival without reducing toxicity. Protecting the full approved dose of 10 milligrams per kilogram through optimized supportive care, rather than preemptive dose cutting, appears to be the wiser path for patients who can tolerate it.

Complicating the picture further is the fact that the optimal timing of growth factor administration alongside antibody-drug conjugates remains poorly defined. Sacituzumab govitecan is given on days 1 and 8 of each 21-day cycle, and the conjugate has a longer half-life than its cytotoxic payload, SN-38, leaving uncertainty about which cycle day best accommodates short-acting or long-acting G-CSF. Practical recommendations advise avoiding growth factor administration within 24 hours of cytotoxic treatment, but systematic evidence for the ideal schedule is lacking. Pharmacogenetics adds another layer of complexity: the UGT1A1*28 polymorphism, which impairs metabolism of SN-38, has been associated in some studies with increased toxicity, though the evidence remains inconsistent and testing was not performed in this cohort.

The stakes of getting this right are only set to rise. With the ASCENT-03 trial demonstrating a progression-free survival benefit for sacituzumab govitecan in previously untreated patients and the ASCENT-04 trial supporting its combination with pembrolizumab in the first line for PD-L1-positive disease, the drug is moving earlier into the treatment course, where patients may have less cumulative bone marrow damage but will face longer durations of exposure. The authors of the new study are careful to note that their findings, drawn from later-line patients, should be extrapolated cautiously to first-line use. For now, the message for clinicians managing metastatic triple-negative breast cancer today is one of calibrated vigilance: reserve upfront growth factor support for patients whose individual risk factors justify it, monitor the rest closely, and intervene promptly when blood counts fall. In supportive care, as this large real-world experiment makes clear, more is not always better.

Subject of Research: Primary G-CSF prophylaxis in sacituzumab govitecan treatment of metastatic triple-negative breast cancer

Article Title: Primary G-CSF prophylaxis in sacituzumab govitecan–treated mTNBC: real-world evidence from a multinational CEBCC-102 cohort

Article References: Mirosława, P., Anna, P.-G., Aleksandra, K., Małgorzata, P., Justyna, Ż., Miloš, H., Renata, S., Hana, Š., Miroslava, M., Agnieszka, M., Karolina, W.-S., Maja, L.-H., Anika, P., Daniel, K., Jan, Š., Iveta, K., Iwona, D., Magdalena, S.-R., Tomasz, C., … Marcin, K. (2026). Primary G-CSF prophylaxis in sacituzumab govitecan–treated mTNBC: real-world evidence from a multinational CEBCC-102 cohort. Supportive Care in Cancer, 34(10), Article 1030. https://doi.org/10.1007/s00520-026-11274-w

Image Credits: AI Generated

DOI: 10.1007/s00520-026-11274-w

Keywords: sacituzumab govitecan, triple-negative breast cancer, G-CSF, neutropenia, febrile neutropenia, supportive care, real-world evidence, antibody-drug conjugate, chemotherapy-induced neutropenia, CEBCC-102, risk-adapted prophylaxis, oncology