Cancer therapy-induced thrombocytopenia, a potentially treatment-limiting fall in platelet numbers, is drawing renewed attention after a multicenter phase II trial reported encouraging results with the oral thrombopoietin receptor agonist hetrombopag in patients with breast cancer. The randomized exploratory study, conducted in China and registered under ClinicalTrials.gov identifier NCT05394285, examined whether the drug could not only help restore platelet counts after severe thrombocytopenia had developed, but also reduce the risk of the complication recurring during a subsequent cycle of anticancer treatment. The investigators reported an 85.0% response rate during the prevention phase among patients who completed the protocol, with an even higher response rate of 89.4% in the subgroup receiving antibody-drug conjugates, or ADCs. The findings suggest that supporting platelet production between treatment cycles could help preserve the continuity of cancer therapy, although the small, non-definitive trial requires confirmation in larger studies.
Thrombocytopenia is a frequent consequence of systemic cancer treatment. Platelets, also known as thrombocytes, are small blood components that gather at sites of vascular injury and initiate clot formation. When their numbers fall substantially, patients may develop bruising, nosebleeds, mucosal bleeding or, in severe cases, potentially life-threatening hemorrhage. In oncology, the problem has consequences beyond bleeding itself. Low platelet counts can force clinicians to delay a treatment cycle, reduce drug doses or interrupt an effective regimen. Such modifications may be particularly consequential for breast cancer patients receiving intensive therapies or ADCs, which link targeted antibodies to cytotoxic payloads and deliver those compounds to tumor cells. The study’s authors describe cancer therapy-induced thrombocytopenia, or CTIT, as a complication that can compromise treatment intensity and potentially affect outcomes.
The trial enrolled patients whose platelet counts fell below 50 × 10⁹ per liter during the first cycle of anticancer therapy. This threshold represents severe thrombocytopenia in many clinical contexts and identified patients who had already demonstrated a significant vulnerability to treatment-related platelet suppression. Between September 2022 and May 2025, 67 breast cancer patients entered the study. One participant withdrew informed consent before randomization, leaving 66 patients who were assigned in equal proportions to receive either hetrombopag or subcutaneous recombinant human thrombopoietin, commonly abbreviated rhTPO. Treatment continued until platelet counts rose above 100 × 10⁹ per liter, a period the researchers defined as the thrombocytopenia treatment phase, or TTP. This design allowed the investigators to compare the experimental oral agent with an established biological approach to stimulating platelet recovery.
Hetrombopag belongs to a class of medicines known as thrombopoietin receptor agonists, or TPO-RAs. These drugs imitate or enhance the activity of thrombopoietin, the principal hormone responsible for regulating platelet production. Thrombopoietin binds to the c-Mpl receptor on hematopoietic stem and progenitor cells in the bone marrow, triggering signaling pathways that promote the development of megakaryocytes. These unusually large marrow cells extend cytoplasmic projections into blood vessels and release thousands of platelets into circulation. By activating the same receptor pathway, hetrombopag is intended to increase megakaryocyte maturation and platelet output rather than directly supplying platelets from outside the body. Its oral formulation also distinguishes it from injectable treatments and may offer practical advantages for patients already managing complex cancer-care schedules.
The central feature of the study was its secondary prevention phase, or SPP. After the initial thrombocytopenia treatment period, every participant who proceeded according to the protocol received hetrombopag as a self-controlled intervention during the next anticancer cycle. The drug was administered for 14 days beginning on the first day of Cycle 2. This approach was designed to test whether platelet stimulation could prevent a repeat decline after a patient had already experienced severe CTIT. Rather than comparing separate prevention and control groups, the investigators followed the same patients into the subsequent treatment cycle, allowing each individual’s earlier experience to provide context for the prevention assessment. The primary endpoint was the proportion of patients who responded during this prevention phase, while platelet-related measures and safety outcomes were also recorded.
Of the 66 randomized patients, six discontinued participation during the secondary prevention phase. The remaining 60 patients formed the per-protocol set used for the primary analysis. Among them, 51 met the study’s criteria for response, producing the reported rate of 85.0%. The response was especially notable among patients treated with ADCs: 42 of 47 patients in that subgroup responded, corresponding to 89.4%. ADC-based regimens included therapies such as trastuzumab emtansine, known as T-DM1, and trastuzumab deruxtecan, or T-DXd, although the supplied report does not provide a separate response figure for every individual drug regimen. These treatments can cause clinically meaningful marrow suppression, and the high response rate in this group suggests that hetrombopag may be particularly relevant where ADC-associated platelet decline threatens continued dosing.
The initial treatment phase also produced favorable comparative results. During the TTP, the response rate was 87.9%, or 29 of 33 patients, among those assigned to hetrombopag. In the rhTPO group, 27 of 33 patients responded, for a rate of 81.8%. These results indicate a numerical advantage for hetrombopag, although the trial was not presented as a definitive superiority study and the difference should not be interpreted as proof that one treatment is more effective in all clinical settings. The investigation was exploratory, and the sample size was limited. In addition, the prevention phase did not retain a parallel untreated or alternative-treatment control group, which makes it difficult to separate the drug’s effect from other influences, including changes in treatment exposure, natural recovery of marrow function and individual differences in susceptibility to CTIT.
Safety findings were reassuring within the limits of the study. The investigators reported that no treatment-emergent severe adverse events occurred. This is clinically important because drugs that stimulate platelet production must be evaluated not only for their ability to raise platelet counts but also for possible complications associated with excessive or poorly controlled platelet production. In cancer patients, concerns can include thrombotic events, interactions with anticancer therapy and abnormal blood-count changes. However, the abstract provides no detailed breakdown of all adverse events, their duration, laboratory abnormalities or longer-term follow-up. It therefore supports the conclusion that hetrombopag was well tolerated in this study population, but it does not establish the complete safety profile required for routine use across broader breast cancer populations or other malignancies.
The findings arrive as oncologists seek strategies that can maintain the planned intensity of modern cancer treatment. Unlike chemotherapy-induced thrombocytopenia, which specifically refers to platelet suppression caused by cytotoxic chemotherapy, CTIT encompasses a wider range of anticancer treatments, including targeted agents and ADCs. These therapies can affect platelet production through direct toxicity to marrow progenitors, altered megakaryocyte development or broader effects on the bone marrow environment. A preventive intervention given at the start of a new treatment cycle could, in principle, keep platelet counts above thresholds needed for treatment delivery and reduce the likelihood of delays. Yet the clinical value of preventing low counts ultimately depends on whether it reduces interruptions, preserves dose intensity, lowers bleeding complications or improves patient outcomes. The present trial primarily demonstrates platelet response, not these longer-term endpoints.
The researchers conclude that hetrombopag may be a promising strategy for both managing established CTIT and preventing its recurrence in breast cancer, particularly among patients receiving ADCs. Their results provide a signal for larger, controlled trials that can evaluate different cancer regimens, dosing schedules and patient risk groups while measuring treatment delays, dose reductions, transfusion requirements, bleeding, thrombosis and cancer-control outcomes. Such studies will also need to clarify which patients benefit most, how long prevention should continue and whether platelet stimulation remains effective across repeated cycles. For now, the phase II findings suggest that an oral agent acting on the body’s own platelet-production machinery could become a useful component of supportive oncology care, but the evidence remains preliminary and should be interpreted as a foundation for further validation rather than a change in standard treatment.
Subject of Research: Secondary prevention and treatment of cancer therapy-induced thrombocytopenia in breast cancer patients using hetrombopag.
Article Title: Secondary prevention of cancer therapy-induced thrombocytopenia with hetrombopag in breast cancer: a multicenter, randomized, exploratory phase II trial
Article References: Sun H, Lv H, Chen W, et al. BMC Medicine (2026).
Image Credits: AI Generated
DOI: 10.1186/s12916-026-05156-5
Keywords: Cancer therapy-induced thrombocytopenia; secondary prevention; breast cancer; hetrombopag; recombinant human thrombopoietin; antibody-drug conjugates; platelet counts; thrombopoietin receptor agonists.
