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Clinical Trial
. 2020 Dec 18;22(12):1851-1861.
doi: 10.1093/neuonc/noaa107.

A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01)

Carmen Balana  1   2 , Maria Angeles Vaz  3 , Juan Manuel Sepúlveda  4 , Carlos Mesia  5 , Sonia Del Barco  6 , Estela Pineda  7 , Jose Muñoz-Langa  8 , Anna Estival  1   2 , Ramón de Las Peñas  9 , Jose Fuster  10 , Regina Gironés  8 , Luis Miguel Navarro  11 , Miguel Gil-Gil  5   12 , Miriam Alonso  13 , Ana Herrero  14 , Sergio Peralta  15 , Clara Olier  16 , Pedro Perez-Segura  17 , Maria Covela  18 , Maria Martinez-García  19 , Alfonso Berrocal  20 , Oscar Gallego  21 , Raquel Luque  22 , Franciso Javier Perez-Martín  5   12 , Anna Esteve  2 , Nuria Munne  23 , Marta Domenech  1 , Salvador Villa  24 , Carolina Sanz  23 , Cristina Carrato  23
Affiliations
Clinical Trial

A phase II randomized, multicenter, open-label trial of continuing adjuvant temozolomide beyond 6 cycles in patients with glioblastoma (GEINO 14-01)

Carmen Balana et al. Neuro Oncol. .

Abstract

Background: Standard treatment for glioblastoma is radiation with concomitant and adjuvant temozolomide for 6 cycles, although the optimal number of cycles of adjuvant temozolomide has long been a subject of debate. We performed a phase II randomized trial investigating whether extending adjuvant temozolomide for more than 6 cycles improved outcome.

Methods: Glioblastoma patients treated at 20 Spanish hospitals who had not progressed after 6 cycles of adjuvant temozolomide were centrally randomized to stop (control arm) or continue (experimental arm) temozolomide up to a total of 12 cycles at the same doses they were receiving in cycle 6. Patients were stratified by MGMT methylation and measurable disease. The primary endpoint was differences in 6-month progression-free survival (PFS). Secondary endpoints were PFS, overall survival (OS), and safety (Clinicaltrials.gov NCT02209948).

Results: From August 2014 to November 2018, 166 patients were screened, 7 of whom were ineligible. Seventy-nine patients were included in the stop arm and 80 in the experimental arm. All patients were included in the analyses of outcomes and of safety. There were no differences in 6-month PFS (control 55.7%; experimental 61.3%), PFS, or OS between arms. MGMT methylation and absence of measurable disease were independent factors of better outcome. Patients in the experimental arm had more lymphopenia (P < 0.001), thrombocytopenia (P < 0.001), and nausea and vomiting (P = 0.001).

Conclusions: Continuing temozolomide after 6 adjuvant cycles is associated with greater toxicity but confers no additional benefit in 6-month PFS.

Key points: 1. Extending adjuvant temozolomide to 12 cycles did not improve 6-month PFS.2. Extending adjuvant temozolomide did not improve PFS or OS in any patient subset.3. Extending adjuvant temozolomide was linked to increased toxicities.

Keywords: MGMT methylation; extended adjuvant temozolomide; glioblastoma; prognosis.

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Figures

Fig. 1
Fig. 1
CONSORT diagram showing flow of patients through the trial (TMZ, temozolomide).
Fig. 2
Fig. 2
(A) PFS and (B) OS for all patients according to treatment arm.
Fig. 3
Fig. 3
Hazard ratios with forest plot for (A) PFS and (B) OS according to stratification factors and treatment arm.
Fig. 4
Fig. 4
(A) PFS and (B) OS for patients with MGMT methylation in the control and experimental arms.
See this image and copyright information in PMC

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