Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors

Margaret Shatara; Megan Blue; Joseph Stanek; Yin A Liu; Daniel M Prevedello; Pierre Giglio; Vinay K Puduvalli; Sharon L Gardner; Jeffrey C Allen; Kenneth K Wong; Marvin D Nelson; Floyd H Gilles; Roberta H Adams; Jasmine Pauly; Katrina O'Halloran; Ashley S Margol; Girish Dhall; Jonathan L Finlay

doi:10.1093/nop/npad067

Final report of the phase II NEXT/CNS-GCT-4 trial: GemPOx followed by marrow-ablative chemotherapy for recurrent intracranial germ cell tumors

Neurooncol Pract. 2023 Oct 14;11(2):188-198. doi: 10.1093/nop/npad067. eCollection 2024 Apr.

Authors

Margaret Shatara¹, Megan Blue², Joseph Stanek², Yin A Liu³, Daniel M Prevedello⁴, Pierre Giglio⁵, Vinay K Puduvalli⁶, Sharon L Gardner⁷, Jeffrey C Allen⁷, Kenneth K Wong^{8

9}, Marvin D Nelson¹⁰, Floyd H Gilles¹¹, Roberta H Adams¹², Jasmine Pauly¹³, Katrina O'Halloran⁸, Ashley S Margol⁸, Girish Dhall¹⁴, Jonathan L Finlay²

Affiliations

¹ Division of Hematology and Oncology, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, Missouri, USA.
² Division of Hematology, Oncology, Blood and Marrow Transplant, Nationwide Children's Hospital and Ohio State University College of Medicine, Columbus, Ohio, USA.
³ Departments of Ophthalmology, Neurology, and Neurosurgery, University of California, Davis, Sacramento, California, USA.
⁴ Department of Neurological Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
⁵ Division of Neuro-Oncology, Ohio State University Wexner Medical Center, James Cancer Center, Columbus, Ohio, USA.
⁶ Department of Neuro-oncology, MD Anderson Cancer Center, Houston, Texas, USA.
⁷ Department of Pediatrics, New York University Grossman School of Medicine, New York, New York, USA.
⁸ Division of Hematology and Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles and Keck School of Medicine of University of Southern California, Los Angeles, California, USA.
⁹ Department of Radiation Oncology, University of Southern California, Los Angeles, California, USA.
¹⁰ Department of Radiology, Children's Hospital of Los Angeles, Los Angeles, California, USA.
¹¹ Department of Pathology, Children's Hospital of Los Angeles, Los Angeles, California, USA.
¹² Phoenix Children's Center for Cancer & Blood Disorders, University of Arizona School of Medicine-Phoenix, and Mayo Clinic, Arizona, USA.
¹³ Division of Hematology and Oncology, Cancer and Blood Disease Institute, Children's Hospital Los Angeles, California, USA.
¹⁴ Division of Pediatric Hematology/Oncology, Children's Hospital of Alabama and the University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

Background: Patients with relapsed intracranial germinoma can achieve durable remission with standard chemotherapy regimens and/or reirradiation; however, innovative therapies are required for patients with relapsed and/or refractory intracranial nongerminomatous germ cell tumors (NGGCTs) due to their poor prognosis. Improved outcomes have been reported using reinduction chemotherapy to achieve minimal residual disease, followed by marrow-ablative chemotherapy (HDCx) with autologous hematopoietic progenitor cell rescue (AuHPCR). We conducted a phase II trial evaluating the response and toxicity of a 3-drug combination developed for recurrent intracranial germ cell tumors consisting of gemcitabine, paclitaxel, and oxaliplatin (GemPOx).

Methods: A total of 9 patients with confirmed relapsed or refractory intracranial GCT were enrolled after signing informed consent, and received at least 2 cycles of GemPOx, of which all but 1 had relapsed or refractory NGGCTs. One patient with progressive disease was found to have pathologically confirmed malignant transformation to pure embryonal rhabdomyosarcoma (without GCT elements), hence was ineligible and not included in the analysis. Patients who experienced sufficient responses proceeded to receive HDCx with AuHPCR. Treatment response was determined based on radiographic tumor assessments and tumor markers.

Results: A total of 7 patients achieved sufficient response and proceeded with HDCx and AuHPCR, and 5 subsequently received additional radiotherapy. A total of 2 patients developed progressive disease while receiving GemPOx. Myelosuppression and transaminitis were the most common treatment-related adverse events. With a mean follow-up of 44 months, 4 patients (3 NGGCTs, 1 germinoma) are alive without evidence of disease.

Conclusions: GemPOx demonstrates efficacy in facilitating stem cell mobilization, thus facilitating the feasibility of both HDCx and radiotherapy.

Keywords: GemPOx; long-term survival; objective response rate; outcomes; relapsed intracranial GCTs.

© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.