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First analysis of EORTC trial 26951, a
randomized phase III study of adjuvant PCV chemotherapy in patients
with highly anaplastic oligodendroglioma
M. J. van den Bent, J. Delattre, A.
A. Brandes, M. J. Taphoorn, K. Hoang Xuan, H. Bernsen, M. Frenay, W.
Grisold, T. Gorlia, D. Lacombe
Daniel den Hoed Oncology Ctr,
Rotterdam, The Netherlands; Federation de Neurologie Mazarin, Groupe
Hospitalier Pitié Salpetriere, Paris, France; Azienda
Ospedale-Universita of Padova, Padova, Italy; Medisch Centrum
Haaglanden, The Hague, The Netherlands; Canisius Wilhemina Ziekenhuis,
Nijmegen, The Netherlands; Ctr Antoine Lacassagne, Nice, France;
Kaiser Frans Joseph Spital, Vienna, Austria; EORTC Datacenter,
Brussels, Belgium
Background. Anaplastic
oligodendroglioma are sensitive to chemotherapy.
EORTC 26951 was initiated to investigate
whether the addition of 6 cycles PCV chemotherapy after radiotherapy
(RT) improves overall survival (OS) and progression free survival
(PFS).
Methods. Eligibility
criteria: histologically confirmed newly diagnosed anaplastic
oligodendroglioma (AOD) or anaplastic oligoastrocytoma (AOA) with
≥ 25% oligodendral elements; age between 18-70 years; ECOG
Performance Status (PS) 0-2; written informed consent.
After stratification for age, institution,
extent of resection, ECOG PS, and prior surgery for a low grade
oligodendroglioma patients were randomized to either 33 x 1.8 Gy
radiotherapy (control arm) or to the same radiotherapy followed by 6
cycles of standard PCV chemotherapy (PCV arm).
Primary endpoint was overall survival,
with PFS as a secondary endpoint.
Results. 368 patients
were randomised, 185 to the PCV arm and 183 patients to the control
arm.
Median follow-up is 4.1 years, 204
patients (55.4%) have died.
Treatment groups were well balanced with
respect to known prognostic factors.
The median number of administered PCV
cycles was 3; 35% of patients completed at least 5 cycles.
At recurrence, PCV chemotherapy was given
to 64% of patients in the control arm vs to 11% in the PCV arm.
In addition, 51% of the patients in the
PCV arm and 48% of patients in the control arm received other
chemotherapy (mostly temozolomide) at recurrence.
PFS was significantly increased after
adjuvant PCV chemotherapy (table; hazard ratio (HR) 0.69; 95%
confidence interval (CI) [0.53;0.88], p = 0.0035).
However, no difference in OS was observed
(HR 0.88; 95% CI [0.67;1.16].
Conclusion. Adjuvant PCV
chemotherapy prolongs PFS from 13 months to 24 months in AOD/AOA,
without a statistically significant improvement of OS.
Analysis of 1p/19q status is in progress.
Overall survival and
progression free survival, between brackets: 95% CI
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Treatment arm
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Median OS (months)
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5 years survival (%)
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Median PFS (months)
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2 years PFS (%)
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RT + PCV
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36.8 [25.1;56.2]
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41.9 [33.6;50.2]
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24.3[17.4;43.8]
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50.9[43.6;58.3]
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RT
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30.0 [21.9;42.2]
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35.0 [26.8;43.3]
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13.3[9.5;21.5]
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40.2[33.0;47.3]
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