The thrombopoietin-receptor agonist romiplostim helps mitigate chemotherapy-induced thrombocytopenia (CIT), reducing related treatment modifications in patients with gastrointestinal cancers, as shown in the landmark phase III RECITE trial.
In a cohort of patients receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers, 84 percent of romiplostim-treated patients did not have to undergo chemotherapy dose modifications due to CIT during cycles 2 and 3 as opposed to only 36 percent of those who received placebo (odds ratio, 10.16, 95 percent confidence interval [CI], 4.44–23.72; risk ratio, 2.77, 95 percent CI, 1.78–4.30; p<0.001 for both). [N Engl J Med 2026;394:1061-1073]
Romiplostim-treated patients also had substantially higher platelet nadirs within three chemotherapy cycles (median, 87 vs 58 × 109/L; p=0.005) and faster time to first platelet response (ie, platelet count of ≥100 × 109/L and no platelet transfusions during the previous 7 days) (1.1 vs 2.1 weeks; p<0.001). The proportion of patients who achieved platelet response was 97 percent with romiplostim vs 77 percent with placebo.
Viable treatment option
“These findings suggest that romiplostim may be a viable therapeutic option for managing CIT in patients with gastrointestinal cancers undergoing oxaliplatin-based chemotherapy,” said lead investigator Dr Hanny Al-Samkari from Massachusetts General Hospital, Boston, Massachusetts, US.
Al-Samkari highlighted the clinical implications of the findings, noting that CIT poses “substantial management challenges” due to the lack of widely available approved treatment.
As a result, “recurring chemotherapy dose reductions or delays, drug omissions or discontinuations, and even discontinuation of chemotherapy treatment [occur], limit[ing] the ability to deliver planned antineoplastic therapy,” he said.
Increased chemo dose intensity
In a post hoc analysis, the median relative dose intensity of delivered chemotherapy across the three cycles was higher in the romiplostim arm at 98 percent vs 77 percent in the placebo arm. The proportion of patients who received all three planned chemotherapy cycles was 95 percent with romiplostim vs 73 percent with placebo.
However, “whether the improved relative dose intensity that can be achieved with romiplostim is sufficient to have an effect on response and survival endpoints is not yet proven,” Al-Samkari pointed out.
Over 1 year of follow-up, death occurred in 53 percent of patients in the romiplostim arm and in 45 percent of those in the placebo arm, with the most common reason being progressive disease (71 percent vs 72 percent, respectively). No deaths were attributed to adverse events (AEs) considered to be related to romiplostim or placebo, Al-Samkari noted.
Further investigation is required to establish the effect of the apparent incremental increase in relative chemotherapy dose intensity with romiplostim on response and survival, he added.
Unanswered questions
“These sweeping results usher in a potentially transformative era of growth-factor treatment for CIT, providing a strong rationale for the use of romiplostim in chemotherapy for solid tumours when the risk of CIT is predicted to be high, with the goal of maximizing relative dose intensity,” wrote Drs George Goshua and Alfred Ian Lee from Yale School of Medicine, New Haven, Connecticut, US, in an editorial. [N Engl J Med 2026;394:1125-1126
Nevertheless, Goshua and Lee noted that despite RECITE’s success, there are still questions needed to be addressed: “Is the effect of romiplostim on CIT consistent across tumour types and chemotherapy regimens? How about targeted therapies and immune checkpoint inhibitors? Will other thrombopoietin-receptor agonists be similarly effective?”
Regarding the lack of benefit seen in terms of overall survival, Goshua and Lee proposed several possible explanations.
“One is that the majority of patients in the trial had metastatic disease, in which the benefit of increasing the relative dose intensity of chemotherapy is less certain. Second, it is possible that the increased relative dose intensity during the second and third cycles of chemotherapy that was made possible by romiplostim was insufficient to affect patient survival,” they said.
“In the future, maximizing relative dose intensity with treatment strategies in which immune priming synergizes with immunotherapy in select cancers may be a particularly salient testing arena for thrombopoietin-receptor agonists in CIT,” they added.
RECITE trial
RECITE included 165 patients (median age 63 years, 24 percent Hispanic, median platelet count 69 x 109/L) with colorectal (75 percent), gastroesophageal (13 percent), or pancreatic (12 percent) cancer. These patients were randomly assigned to receive weekly subcutaneous doses of romiplostim (n=109) or placebo (n=56) for three chemotherapy cycles.
Duration-adjusted rates of grade ≥2 bleeding events did not significantly differ between the romiplostim and placebo arms, at 4 and 7.6 per 100 patient-years (hazard ratio, 0.53, 95 percent CI, 0.04–6.77; p=0.63), respectively.
In terms of safety, grade ≥3 AEs occurred in 37 percent of patients in the romiplostim arm vs 22 percent in the placebo arm, which primarily reflected chemotherapy effects, according to Al-Samkari. AEs considered to be related to the study drugs were documented in 12 percent and 7 percent of patients in the respective group, with the most common being nausea and headache. None of these events led to death or discontinuation of romiplostim, placebo, or chemotherapy.
Thromboembolic events occurred in 2 percent of patients in the romiplostim arm only.