Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia

Author(s): Hanny Al-Samkari, M.D.¹; César Muñoz, M.D.^2,3,4; Çağlayan Geredeli, M.D.^5,6; Ippokratis Korantzis, M.D., Ph.D.⁷; Beatriz González Astorga, M.D.⁸; Cagatay Arslan, M.D.⁹; Johnny Francisco Cordeiro Camargo, M.D.¹⁰; Florian Scotté, M.D., Ph.D.¹¹; Giuliano Borges, M.D.¹²; Kejia Wang, Ph.D.¹³; Melissa Eisen, M.D.¹⁴; David J. Kuter, M.D., D.Phil.¹; Gerald A. Soff, M.D.¹⁵;

Source: DOI: 10.1056/NEJMoa2511882

Dr. Anjan Patel's Thoughts

This is the first phase 3 data we’ve had for chemotherapy-induced thrombocytopenia, and romiplostim really moved the needle, 84% of patients were able to avoid CIT-driven dose reductions or delays versus just 36% with placebo, with a risk ratio of 2.8. Platelet nadirs were higher, responses were faster (median ≈1 week), and relative dose intensity was meaningfully better maintained across cycles. Bleeding wasn’t significantly different, but events were numerically lower, and this study wasn’t powered for that. Toxicity was largely chemo-related, with a small signal for thromboembolism (2%), so overall this feels like a practical tool to help maintain dose intensity in gastrointestinal tract (GI) cancers getting oxaliplatin-based regimens.

BACKGROUND

Chemotherapy-induced thrombocytopenia (CIT) is a common complication of chemotherapy that is associated with bleeding, reduced relative dose intensity, and potentially worse outcomes. No widely available therapies are approved for CIT.

METHODS

We conducted a phase 3, international, double-blind, randomized, placebo-controlled trial involving patients with persistent CIT (platelet count, ≤85×109 per liter on trial day 1) who were receiving oxaliplatin-based multiagent cytotoxic chemotherapy for gastrointestinal cancers. Patients were randomly assigned in a 2:1 ratio to receive romiplostim or placebo for three chemotherapy cycles. The primary end point was the absence of CIT-induced modifications of the chemotherapy dose (reduction, delay, omission, or discontinuation) in both the second and third chemotherapy cycles. Research Summary Romiplostim versus Placebo for Chemotherapy-Induced Thrombocytopenia

RESULTS

Of the 165 patients who underwent randomization (109 in the romiplostim group and 56 in the placebo group), 75% had colorectal cancer, 13% had gastroesophageal cancer, and 12% had pancreatic cancer; 72% of the patients in the romiplostim group and 61% of those in the placebo group had stage 4 disease. The percentage of patients with no CIT-induced modifications of the chemotherapy dose was 84% (92 of 109 patients) with romiplostim and 36% (20 of 56 patients) with placebo, which corresponded to an odds ratio of 10.16 (95% confidence interval [CI], 4.44 to 23.72; P

CONCLUSIONS

In this phase 3, placebo-controlled trial, romiplostim was efficacious in treating CIT. (Funded by Amgen and the Biomedical Advanced Research and Development Authority; RECITE ClinicalTrials.gov number, NCT03362177.)

Author Affiliations

¹Division of Classical Hematology, Mass General Brigham Cancer Institute, Massachusetts General Hospital, Boston; ²Medical Oncology, Centro Integral Oncológico Clara Campal, Hospital Universitario HM Sanchinarro, HM Hospitales, Madrid; ³Facultad HM de Ciencias de la Salud de la Universidad Camilo José Cela, Madrid; ⁴Instituto de Investigación Sanitaria HM Hospitales, Madrid; ⁵Department of Medical Oncology, Gaziosmanpaşa Medical Park Hospital, Istanbul, Turkey; ⁶Department of Internal Medicine, İstinye University Faculty of Medicine, Istanbul, Turkey; ⁷Oncology Department, St. Luke’s Hospital–Agios Loukas Clinic, Thessaloniki, Greece; ⁸Medical Oncology, Hospital Universitario Clínico San Cecilio, Granada, Spain; ⁹Medical Oncology Department, Izmir University of Economics, MedicalPoint International Hospital, Izmir, Turkey; ¹⁰Oncology Department, Instituto de Oncologia do Paraná, Oncoville, Curitiba, Brazil; ¹¹Interdisciplinary Cancer Course Department, Institut Gustave Roussy, Villejuif, France; ¹²Oncology Department, Catarina Pesquisa Clínica–Clínica de Neoplasias Litoral, Itajaí, Brazil; ¹³Biostatistics, Amgen, Thousand Oaks, CA; ¹⁴Clinical Development, Amgen, Thousand Oaks, CA; ¹⁵Medicine Department, Hematology Division, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami

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