TOPLINE:

Among patients with gastrointestinal (GI) cancers and persistent chemotherapy-induced thrombocytopenia, those who received romiplostim were nearly three times as likely to avoid chemotherapy dose modifications due to thrombocytopenia than those receiving placebo.

METHODOLOGY:

• Chemotherapy-induced thrombocytopenia, a common complication of myelosuppressive chemotherapy, is typically managed by reducing chemotherapy doses or delaying or discontinuing treatment. There are currently no FDA-approved therapies specifically for chemotherapy-induced thrombocytopenia.
• In the current randomized phase 3 study, researchers assessed the safety and efficacy of romiplostim to treat chemotherapy-induced thrombocytopenia among patients with colorectal, gastroesophageal, or pancreatic cancer.
• Overall, 165 patients with GI cancers of all stages receiving oxaliplatin-based chemotherapy and with persistent chemotherapy-induced thrombocytopenia (platelet count < 85 × 10⁹/L) were randomly assigned to receive romiplostim (n = 109) or placebo (n = 56) over three chemotherapy cycles.
• Romiplostim (or placebo) was administered subcutaneously weekly with doses adjusted to maintain platelet counts of 100-250 × 10⁹/L, starting from trial day 1 through chemotherapy reinitiation and up to three additional chemotherapy cycles.
• The primary endpoint was the absence of treatment modifications to chemotherapy dose (reduction, delay, omission, or discontinuation) due to chemotherapy-induced thrombocytopenia in both the second and third chemotherapy cycles. Key secondary endpoints included platelet nadir during treatment and time to platelet response (platelet count > 100 × 10⁹/L without transfusions). The analysis did not assess survival outcomes.

TAKEAWAY:

• Patients receiving romiplostim were substantially more likely to avoid chemotherapy dose modifications due to thrombocytopenia (84% vs 36%), corresponding to about 10-fold higher odds (odds ratio, 10.16) and a nearly threefold higher likelihood (relative risk, 2.77).
• Median platelet nadirs during the treatment period were higher with romiplostim than with placebo (87 × 10⁹/L vs 58 × 10⁹/L; P = .005). In post hoc analyses, the median time to first platelet response was faster with romiplostim than with placebo (1.1 vs 2.1 weeks; hazard ratio, 2.67), with platelet responses observed in 97% of patients with romiplostim and 77% with placebo.
• A higher proportion of patients receiving romiplostim completed all three planned chemotherapy cycles (95% vs 73%).
• Adverse events of grade 3 or higher occurred more frequently in the romiplostim group (37% vs 22%), largely reflecting chemotherapy-related toxic effects, with no clear new safety signal.

IN PRACTICE:

“These sweeping results usher in a potentially transformative era of growth factor treatment for [chemotherapy-induced thrombocytopenia], providing a strong rationale for the use of romiplostim in chemotherapy for solid tumors when the risk of [chemotherapy-induced thrombocytopenia] is predicted to be high,” wrote authors of an accompanying editorial, George Goshua, MD, SM, and Alfred Ian Lee, MD, PhD, Yale School of Medicine, New Haven, Connecticut. “Still, many questions remain,” which include “whether the apparent incremental increase in relative dose intensity resulting from this intervention will allow more patients to have a response to treatment or to have longer responses and thus will ultimately improve survival.”

SOURCE:

The study, led by Hanny Al-Samkari, MD, Division of Classical Hematology, Mass General Brigham Cancer Institute, Massachusetts General Hospital, Boston, was published online in The New England Journal of Medicine, alongside an accompanying editorial.

LIMITATIONS:

Interpretation of cancer outcomes was inherently limited by the three-cycle intervention period for chemotherapy-induced thrombocytopenia and the lack of standardized follow-up beyond this period because post-trial therapy was managed at the investigator’s discretion. Baseline imbalances between trial groups with respect to Eastern Cooperative Oncology Group performance-status score, disease stage, number of previous treatment lines, and previous or concurrent bevacizumab use, together with heterogeneity of the patient population across tumor types, stages, chemotherapy regimens, and lines of therapy, may have confounded interpretation of oncologic endpoints. The duration of follow-up and the number of participants are insufficient to rule out a potential risk for myelodysplastic syndrome or secondary cancer with romiplostim.

DISCLOSURES:

The study was supported by Amgen and the Biomedical Advanced Research and Development Authority. Al-Samkari disclosed receiving grants and fees from various organizations. Gerald A. Soff disclosed having financial relationships with multiple companies. Additional disclosures are noted in the article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.