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Effect of Vocimagene Amiretrorepvec in Combination With Flucytosine vs Standard of Care on Survival Following Tumor Resection in Patients With Recurrent High-Grade Glioma: A Randomized Clinical Trial.
Cloughesy, Timothy F; Petrecca, Kevin; Walbert, Tobias; Butowski, Nicholas; Salacz, Michael; Perry, James; Damek, Denise; Bota, Daniela; Bettegowda, Chetan; Zhu, Jay-Jiguang; Iwamoto, Fabio; Placantonakis, Dimitris; Kim, Lyndon; Elder, Brad; Kaptain, George; Cachia, David; Moshel, Yaron; Brem, Steven; Piccioni, David; Landolfi, Joseph; Chen, Clark C; Gruber, Harry; Rao, Aliz R; Hogan, Daniel; Accomando, William; Ostertag, Derek; Montellano, Tiffany T; Kheoh, Thian; Kabbinavar, Fairooz; Vogelbaum, Michael A.
Afiliación
  • Cloughesy TF; University of California, Los Angeles, Los Angeles, California.
  • Petrecca K; Montreal Neurological Institute, Montreal, Quebec, Canada.
  • Walbert T; Henry Ford Hospital, Detroit, Michigan.
  • Butowski N; University of California, San Francisco, San Francisco, California.
  • Salacz M; University of Kansas Medical Center, Kansas City, Kansas.
  • Perry J; Sunnybrook Research Institute, Sunnybrook Hospital, Toronto, Canada.
  • Damek D; University of Colorado, Aurora, Colorado.
  • Bota D; University of California, Irvine, Irvine, California.
  • Bettegowda C; Johns Hopkins University School of Medicine, Baltimore, Maryland.
  • Zhu JJ; University of Texas Health Science Center, Houston, Texas.
  • Iwamoto F; Columbia University, New York, New York.
  • Placantonakis D; New York University Langone Medical Center, New York, New York.
  • Kim L; Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Elder B; Mount Sinai Hospital, New York, New York.
  • Kaptain G; Ohio State University, Columbus, Ohio.
  • Cachia D; John Theurer Cancer Center, Hackensack University, Hackensack, New Jersey.
  • Moshel Y; Medical University of South Carolina, Charleston, South Carolina.
  • Brem S; Overlook Medical Center, Summit, New Jersey.
  • Piccioni D; Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
  • Landolfi J; University of California San Diego, San Diego, California.
  • Chen CC; JFK Medical Center, Edison, New Jersey.
  • Gruber H; University of Minnesota, Minneapolis, Minnesota.
  • Rao AR; Formerly Tocagen Inc, San Diego, California.
  • Hogan D; AmpiSwitch, San Diego, California.
  • Accomando W; Formerly Tocagen Inc, San Diego, California.
  • Ostertag D; Bionano Genomics, San Diego, California.
  • Montellano TT; Formerly Tocagen Inc, San Diego, California.
  • Kheoh T; Impossible Foods, San Francisco, California.
  • Kabbinavar F; Formerly Tocagen Inc, San Diego, California.
  • Vogelbaum MA; Fate Therapeutics, San Diego, California.
JAMA Oncol ; 6(12): 1939-1946, 2020 12 01.
Article en En | MEDLINE | ID: mdl-33119048
ABSTRACT
Importance New treatments are needed to improve the prognosis of patients with recurrent high-grade glioma.

Objective:

To compare overall survival for patients receiving tumor resection followed by vocimagene amiretrorepvec (Toca 511) with flucytosine (Toca FC) vs standard of care (SOC). Design, Setting, and

Participants:

A randomized, open-label phase 2/3 trial (TOCA 5) in 58 centers in the US, Canada, Israel, and South Korea, comparing posttumor resection treatment with Toca 511 followed by Toca FC vs a defined single choice of approved (SOC) therapies was conducted from November 30, 2015, to December 20, 2019. Patients received tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma.

Interventions:

Patients were randomized 11 to receive Toca 511/FC (n = 201) or SOC control (n = 202). For the Toca 511/FC group, patients received Toca 511 injected into the resection cavity wall at the time of surgery, followed by cycles of oral Toca FC 6 weeks after surgery. For the SOC control group, patients received investigators' choice of single therapy lomustine, temozolomide, or bevacizumab. Main Outcomes and

Measures:

The primary outcome was overall survival (OS) in time from randomization date to death due to any cause. Secondary outcomes reported in this study included safety, durable response rate (DRR), duration of DRR, durable clinical benefit rate, OS and DRR by IDH1 variant status, and 12-month OS.

Results:

All 403 randomized patients (median [SD] age 56 [11.46] years; 62.5% [252] men) were included in the efficacy analysis, and 400 patients were included in the safety analysis (3 patients on the SOC group did not receive resection). Final analysis included 271 deaths (141 deaths in the Toca 511/FC group and 130 deaths in the SOC control group). The median follow-up was 22.8 months. The median OS was 11.10 months for the Toca 511/FC group and 12.22 months for the control group (hazard ratio, 1.06; 95% CI 0.83, 1.35; P = .62). The secondary end points did not demonstrate statistically significant differences. The rates of adverse events were similar in the Toca 511/FC group and the SOC control group. Conclusions and Relevance Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points. Trial Registration ClinicalTrials.gov Identifier NCT02414165.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Citosina Desaminasa / Flucitosina / Glioma / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: JAMA Oncol Año: 2020 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Neoplasias Encefálicas / Citosina Desaminasa / Flucitosina / Glioma / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: JAMA Oncol Año: 2020 Tipo del documento: Article