Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis

Authors

Wendy Allen-Rhoades, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Minnesota, Rochester, USA
Philip J. Lupo, Department of Pediatrics, Baylor College of Medicine, Texas, Houston, USA
Michael E. Scheurer, Department of Pediatrics, Baylor College of Medicine, Texas, Houston, USA
Yueh-Yun Chi, Cancer and Blood Disease Institute, Children's Hospital of Los Angeles, Norris Comprehensive Cancer Center and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
John F. Kuttesch, Department of Pediatrics, University of New Mexico, Albuquerque, New Mexico, USA
Rajkumar Venkatramani, Department of Pediatrics, Baylor College of Medicine, Texas, Houston, USA
William H. Meyer, Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Leo Mascarenhas, Cancer and Blood Disease Institute, Children's Hospital of Los Angeles, Norris Comprehensive Cancer Center and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA

Document Type

Article

Publication Date

5-1-2023

Abstract

BACKGROUND: Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide.

AIMS: The goal of our study was to evaluate whether RMS histology subtype influences response rate to vinorelbine alone or in combination.

MATERIALS & METHODS: Five Phase 2 trials that enrolled RMS patients were included in the meta-analysis. Two studies evaluated vinorelbine alone, two studies evaluated vinorelbine in combination with low dose oral cyclophosphamide, and one study evaluated vinorelbine and intravenous cyclophosphamide in combination with temsirolimus or bevacizumab. All RMS patients had relapsed or refractory disease and had received at least one prior therapy. Response was reported according to RECIST1.1 and was defined as a complete or partial response. Response data was obtained from published results or from trial principal investigator. RMS NOS patients were grouped with ERMS patients for this analysis. Summary estimates comparing differences between ARMS and ERMS response rates were generated using a random-effects model to account for heterogeneity among the studies.

RESULTS: One hundred fifty-six enrolled patients evaluable for response were included in the meta-analysis, 85 ARMS, 64 ERMS and 7 RMS-NOS. The combined effect generated from the random-effects model demonstrated a 41% increase (p = 0.001, 95% CI; 0.21-0.60) in response to vinorelbine as a single agent or in combination in patients with ARMS compared to patients with ERMS. There was no significant difference in the rate of progressive disease between patients with ARMS compared to ERMS (p = 0.1, 95%CI; -0.26-0.02).

DISCUSSION: Vinorelbine is an active agent for the treatment of relapsed or refractory RMS and a meta-analysis of Phase 2 studies shows that radiographic responses in patients with ARMS were significantly higher than ERMS or RMS-NOS.

CONCLUSION: These data support further investigation of vinorelbine in newly diagnosed patients with RMS particularly those with alveolar histology.

Publication Title

Cancer Med

ISSN

2045-7634

Volume

12

Issue

9

First Page

10222

Last Page

10229

DOI

10.1002/cam4.5749

Recommended Citation

Allen-Rhoades W, Lupo PJ, Scheurer ME, Chi YY, Kuttesch JF, Venkatramani R, Meyer WH, Mascarenhas L. Alveolar rhabdomyosarcoma has superior response rates to vinorelbine compared to embryonal rhabdomyosarcoma in patients with relapsed/refractory disease: A meta-analysis. Cancer Med. 2023 May;12(9):10222-10229. doi: 10.1002/cam4.5749. Epub 2023 Apr 4. PMID: 37016270; PMCID: PMC10225185.