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Foster JH, Voss SD, Hall DC, et al. Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clin Cancer Res. 2021;27(13):3543-3548doi: 10.1158/1078-0432.CCR-20-4224.
Foster, J. H., Voss, S. D., Hall, D. C., Minard, C. G., Balis, F. M., Wilner, K., Berg, S. L., Fox, E., Adamson, P. C., Blaney, S. M., Weigel, B. J., & Mossé, Y. P. (2021). Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clinical cancer research : an official journal of the American Association for Cancer Research, 27(13), 3543-3548. https://doi.org/10.1158/1078-0432.CCR-20-4224
Foster, Jennifer H, et al. "Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912)." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 27,13 (2021): 3543-3548. doi: https://doi.org/10.1158/1078-0432.CCR-20-4224
Foster JH, Voss SD, Hall DC, Minard CG, Balis FM, Wilner K, Berg SL, Fox E, Adamson PC, Blaney SM, Weigel BJ, Mossé YP. Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912). Clin Cancer Res. 2021 Jul 01;27(13):3543-3548. doi: 10.1158/1078-0432.CCR-20-4224. Epub 2021 Feb 10. PMID: 33568345; PMCID: PMC8254744.
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Clin Cancer Res. 2021 Jul 01;27(13):3543-3548. doi: 10.1158/1078-0432.CCR-20-4224. Epub 2021 Feb 10.

Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children's Oncology Group Study (ADVL0912).

Clinical cancer research : an official journal of the American Association for Cancer Research

Jennifer H Foster, Stephan D Voss, David C Hall, Charles G Minard, Frank M Balis, Keith Wilner, Stacey L Berg, Elizabeth Fox, Peter C Adamson, Susan M Blaney, Brenda J Weigel, Yael P Mossé

Affiliations

  1. Baylor College of Medicine; Texas Children's Cancer and Hematology Centers, Houston, Texas.
  2. Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts.
  3. Children's Oncology Group, Monrovia, California.
  4. Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
  5. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.
  6. Pfizer Oncology, La Jolla, California.
  7. St Jude Children's Research Hospital, Memphis, Tennessee.
  8. University of Minnesota, Minneapolis, Minnesota.
  9. Division of Oncology and Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. [email protected].

PMID: 33568345 PMCID: PMC8254744 DOI: 10.1158/1078-0432.CCR-20-4224

Abstract

PURPOSE: Anaplastic lymphoma kinase (ALK) aberrations are a promising target for patients with neuroblastoma. We assessed the activity of first-generation ALK inhibitor crizotinib in patients with no known curative treatments and whose tumors harbored an activating ALK alteration.

PATIENTS AND METHODS: Twenty patients with relapsed/refractory ALK-positive neuroblastoma received crizotinib at the recommended phase II dose of 280 mg/m

RESULTS: The objective response rate for patients with neuroblastoma was 15% [95% confidence interval (CI): 3.3%-34.3%]: two with partial responses and 1 with a complete response. All three patients had a somatic ALK Arg1275Gln mutation, the most common ALK hotspot mutation observed in neuroblastoma and the only mutation predicted to be sensitive to ALK inhibition with crizotinib. Two patients had prolonged stable disease (10 and 13 cycles, respectively); both harbored an ALK Arg1275Gln mutation. Three patients with ALK Phe1174Leu mutations progressed during cycle 1 of therapy, and one patient with an ALK Phe1174Val received three cycles before disease progression. The two patients with ALK amplification had no response. The most common adverse event was a decrease in neutrophil count.

CONCLUSIONS: Despite limited activity seen in this trial, we conclude that this is more likely due to an inability to reach the higher concentrations of crizotinib needed to overcome the competing ATP affinity.

©2021 American Association for Cancer Research.

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