Drug Cuts Treatment Modifications From Chemotherapy-Induced Thrombocytopenia

The use of romiplostim (Nplate) reduced treatment modifications due to chemotherapy-induced thrombocytopenia (CIT) in patients with gastrointestinal cancers, a phase III randomized trial showed.

Among 165 patients, 84% of those treated with romiplostim had no CIT-induced modifications of chemotherapy dose compared with 36% of those who received placebo, with an odds ratio of 10.16 (95% CI 4.44-23.72, P<0.001) and a risk ratio of 2.77 (95% CI 1.78-4.30, P<0.001), reported Hanny Al-Samkari, MD, of the Mass General Brigham Cancer Institute and Massachusetts General Hospital in Boston, and colleagues.

Patients who received romiplostim compared with placebo also had higher median nadir platelet counts (87 × 10⁹/L vs 58 × 10⁹/L, P=0.005) and faster time to first platelet response (median 1.1 vs 2.1 weeks, P<0.001), they noted in the New England Journal of Medicine.

Romiplostim, a thrombopoietin receptor agonist, was first approved by the FDA in 2008 for treating thrombocytopenia in adults with chronic immune thrombocytopenic purpura who had not responded to other treatments, but there are no widely available therapies approved for CIT.

“These findings suggest that romiplostim may be a viable therapeutic option for managing CIT in patients with gastrointestinal cancers undergoing oxaliplatin-based chemotherapy,” Al-Samkari and colleagues concluded.

In an editorial accompanying the study, George Goshua, MD, and Alfred Ian Lee, MD, PhD, both of the Yale School of Medicine in New Haven, Connecticut, noted that “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 tumors when the risk of CIT is predicted to be high, with the goal of maximizing relative dose intensity.”

However, they also suggested that questions remain about whether the drug’s effect on CIT will be consistent across tumor types and chemotherapy regimens, or even targeted therapies and immune checkpoint inhibitors, and if other thrombopoietin receptor agonists will be as effective as romiplostim.

In a post hoc analysis, the median relative dose intensity of chemotherapy was 98% with romiplostim and 77% with placebo across the three planned cycles.

“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, and this critical point requires further investigation,” Al-Samkari and colleagues wrote.

While they found that overall survival was actually lower in the romiplostim group (47% vs 55% with placebo), the editorialists said this result could be explained by the fact 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.” They added that it was possible that the increased relative dose intensity made possible by romiplostim during the second and third cycles of chemotherapy was insufficient to affect patient survival.

RECITE was an international, double-blind trial that enrolled 165 patients receiving oxaliplatin-based multiagent cytotoxic chemotherapy for colorectal (75%), gastroesophageal (13%), or pancreatic (12%) cancer who were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles.

Median age was 63 years, the majority were men, 90% were white, 4% were Black, and 24% were Hispanic. Of these patients, 73% had received less than two previous chemotherapy lines, and 84% had received more than two previous chemotherapy cycles.

More patients receiving romiplostim versus placebo had stage IV disease (72% vs 61%), an Eastern Cooperative Oncology Group (ECOG) performance status score of more than 0 (53% vs 41%), at least two previous treatment lines (28% vs 21%), previous bevacizumab (Avastin) use (35% vs 20%), or concurrent bevacizumab use (25% vs 14%).

Patients receiving romiplostim were also more likely to complete their assigned regimen compared with those on placebo (82% vs 61%).

Adverse events (AEs) of grade 3 or higher were reported in 37% of patients taking romiplostim and 22% of patients taking placebo, “which primarily reflected chemotherapy effects,” the authors noted. AEs that were considered by the investigator to be related to romiplostim or placebo occurred in 12% and 7%, respectively.

Serious AEs were reported in 21% and 5% of patients in the romiplostim and placebo groups, but no serious AEs were considered related to romiplostim or placebo, or led to death or discontinuation of romiplostim, placebo, or chemotherapy.

Thromboembolic events occurred in 2% of patients who received romiplostim and no patients who received placebo.

Al-Samkari and colleagues acknowledged that interpretations of cancer outcomes in the trial were limited by the three-cycle intervention period and the lack of a standardized follow-up beyond that period. The study was also limited by baseline imbalances between groups, they added.