Long-term follow-up results of EORTC 26951: A randomized phase III study on adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD).

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. 2-2 ◽  
Author(s):  
Martin J. Van Den Bent ◽  
Khê Hoang-Xuan ◽  
Alba Ariela Brandes ◽  
Johan M Kros ◽  
Mathilde C.M. Kouwenhoven ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Oligodendroglial Tumors ◽  
Tumor Group ◽  
Idh Mutations ◽  
Long Term Follow Up ◽  
Phase Iii Study ◽  
The Difference

2 Background: AOD are chemotherapy-sensitive tumors especially if 1p/19q co-deleted. Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine chemotherapy (PCV) in AOD. We now present long-term follow-up. Methods: Patients (pts) with locally diagnosed newly diagnosed AOD were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles of standard PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression-free survival (PFS). 1p/19q status, IDH status and MGMT promoter methylation were determined in 300, 167, and 186 pts respectively. Results: Between 1996 and 2002, 368 pts were included. At the time of analysis 281 pts (76.4%) had died. Median PFS after RT/PCV was significantly longer compared to RT alone (24.3 months versus 13.21 months, hazard ratio [HR] 0.66, [95% confidence interval (95% CI) 0.52, 0.83]). More RT arm patients received chemotherapy at progression (75% vs 53%). Median OS was also significantly prolonged in the RT/PCV arm (42.3 months vs 30.6 months for the RT arm, HR 0.75 [95% CI 0.60, 0.95]). 1p/19q co-deleted patients (n = 76) treated with RT/PCV had improved OS compared to RT arm pts (median OS not reached vs 113 months; HR 0.54, p = 0.0487). In the 224 patients without 1p/19q co-deletion the difference in OS was non-significant (OS RT/PCV arm 25 months vs 22 months in the RT arm, HR 0.82, p = 0.18; test for interaction p = 0.22). There was a slight trend towards improved OS in MGMT methylated and IDH mutated tumors versus unmethylated and IDH wild type tumors (Table). Conclusions: The addition of PCV to RT increases PFS and OS in AOD. Pts with 1p/19q co-deletion appear to benefit most from the addition of PCV, with a trend for improved OS in pts with MGMT methylation and IDH mutations. [Table: see text]

scholarly journals LTBK-12. EORTC 26951, RANDOMIZED STUDY OF ADJUVANT PCV AFTER 59.4 GY RADIOTHERAPY: VERY LONG TERM FOLLOW-UP

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi285-vi285
Author(s):  
Martin van den Bent ◽  
Khe Hoang-Xuan ◽  
Alba Brandes ◽  
Johan Kros ◽  
M C M Kouwenhoven ◽  
...  
Keyword(s):  
Randomized Study ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Tumor Group ◽  
Long Term Follow Up

Abstract BACKGROUND Between 1995 and 2002 the EORTC Brain Tumor Group conducted a prospective phase III study on adjuvant procarbazine, CCNU and vincristine (PCV) chemotherapy in anaplastic oligodendroglioma (AOD). A mature follow-up presented in 2012 showed survival benefit of the addition of PCV, in particular in 1p/19q co-deleted tumors and tumors with MGMT promoter methylation. We now present very long term follow-up. MATERIALS AND METHODS Patients were eligible if locally diagnosed with a newly diagnosed AOD. They were randomized between radiotherapy (RT, 33 x 1.8 Gy) and the same RT followed by 6 cycles PCV (RT/PCV). Primary endpoints were overall survival (OS) and progression free survival (PFS). 1p/19q status (FISH) was determined in 300 patient. Kaplan- Meier technique and Cox modeling were used for long term survival analysis. Primary analyses were adjusted for known prognostic factors. For other analyses no adjustment was performed. RESULTS With 368 patients included, a median follow-up of 18.4 years and 307 (83%) survival events, median and 20-year survival after RT/PCV versus RT alone were 42.3 mo and 16.8% vs 30.6 months and 10.1% (HR 0.78; 95% CI (0.63, 0.98), adjusted p=0.06). Eighty patients were 1p/19q codel of which 26 (33%) were still alive, in this subgroup median and 20-year survival after RT/PCV versus RT alone were 14 years and 37.1% versus 9.3 years and 13.6% (HR 0.60, 95% CI (0.35, 1.03), unadjusted p=0.06). Twenty year PFS in 1p/19q codel was 31.3% in RT/PCV treated patients and 10.8% in RT only treated patients (HR 0.49, 95% CI (0.29, 0.83), unadjusted p=0.007). In the 1p/19q codel subgroup age, WHO PS and necrosis at pathology were identified to be of independent prognostic value for OS. CONCLUSION This long term analysis confirms the earlier conclusions and provides data on long term survival in this patient group. In 1p/19q codel patients treated with RT/PCV, the 20-year PFS and OS rates are 31% and 37% respectively.

Long-term follow-up results of EORTC 26951: A randomized phase III study on adjuvant PCV chemotherapy in anaplastic oligodendroglial tumors (AOD).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2-2
Author(s):  
Martin J. Van Den Bent ◽  
Khê Hoang-Xuan ◽  
Alba Ariela Brandes ◽  
Johan M Kros ◽  
Mathilde C.M. Kouwenhoven ◽  
...  
Keyword(s):  
Annual Meeting ◽  
Phase Iii ◽  
Daily News ◽  
Online Supplement ◽  
Oligodendroglial Tumors ◽  
Long Term Follow Up ◽  
Phase Iii Study ◽  
Final Text

2 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

Adjuvant Procarbazine, Lomustine, and Vincristine Chemotherapy in Newly Diagnosed Anaplastic Oligodendroglioma: Long-Term Follow-Up of EORTC Brain Tumor Group Study 26951

2013 ◽  
Vol 31 (3) ◽  
pp. 344-350 ◽  
Author(s):  
Martin J. van den Bent ◽  
Alba A. Brandes ◽  
Martin J.B. Taphoorn ◽  
Johan M. Kros ◽  
Mathilde C.M. Kouwenhoven ◽  
...  
Keyword(s):  
Methylation Status ◽  
Prognostic Significance ◽  
Phase Iii ◽  
Anaplastic Oligodendroglioma ◽  
Newly Diagnosed ◽  
Oligodendroglial Tumors ◽  
Mutational Status ◽  
Long Term Follow Up

Purpose Anaplastic oligodendroglioma are chemotherapy-sensitive tumors. We now present the long-term follow-up findings of a randomized phase III study on the addition of six cycles of procarbazine, lomustine, and vincristine (PCV) chemotherapy to radiotherapy (RT). Patients and Methods Adult patients with newly diagnosed anaplastic oligodendroglial tumors were randomly assigned to either 59.4 Gy of RT or the same RT followed by six cycles of adjuvant PCV. An exploratory analysis of the correlation between 1p/19q status and survival was part of the study. Retrospectively, the methylation status of the methyl-guanine methyl transferase gene promoter and the mutational status of the isocitrate dehydrogenase (IDH) gene were determined. The primary end points were overall survival (OS) and progression-free survival based on intent-to-treat analysis. Results A total of 368 patients were enrolled. With a median follow-up of 140 months, OS in the RT/PCV arm was significantly longer (42.3 v 30.6 months in the RT arm, hazard ratio [HR], 0.75; 95% CI, 0.60 to 0.95). In the 80 patients with a 1p/19q codeletion, OS was increased, with a trend toward more benefit from adjuvant PCV (OS not reached in the RT/PCV group v 112 months in the RT group; HR, 0.56; 95% CI, 0.31 to 1.03). IDH mutational status was also of prognostic significance. Conclusion The addition of six cycles of PCV after 59.4 Gy of RT increases both OS and PFS in anaplastic oligodendroglial tumors. 1p/19q-codeleted tumors derive more benefit from adjuvant PCV compared with non–1p/19q-deleted tumors.

Chemotherapy plus radiotherapy (CT-RT) versus RT alone for patients with anaplastic oligodendroglioma: Long-term results of the RTOG 9402 phase III study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008b-2008b ◽  
Author(s):  
J. Gregory Cairncross ◽  
Meihua Wang ◽  
Edward G. Shaw ◽  
Robert B. Jenkins ◽  
Bernd W. Scheithauer ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Long Term Results ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Entire Cohort ◽  
Phase Iii Study

2008b Background: Anaplastic oligodendrogliomas, pure (AO) and mixed (AOA), are chemosensitive tumors, especially if co-deleted for chromosomes 1p and 19q, but whether addition of CT to RT prolongs overall survival (OS), is unknown. Methods: In the RTOG 9402 Phase III trial, patients (pts) with AO/AOA were randomly assigned to PCV [procarbazine, CCNU (lomustine) and vincristine] followed by immediate RT vs. immediate RT alone. Early analysis showed no OS benefit for the PCV+RT group but combined therapy was associated with a longer progression-free survival (PFS). It also showed that the finding of 1p/19q co-deletion was associated with a longer OS independent of treatment. The current analysis has a median follow up of 11.3 years (yrs). Results: Two hundred ninety-one patients were randomized, 148 to PCV+RT and 143 to RT. PCV+RT was associated with longer PFS [2.5 vs. 1.7 yrs, hazard ratio (HR) 0.68, 95% confidence interval (CI) (0.53, 0.88), P = 0.003] and the 1p/19q co-deletion with a longer Median Survival Time (MST) [8.7 vs. 2.7 yrs, HR 0.41, 95% CI (0.30, 0.55), P < 0.001]. For the entire cohort, there was no difference in MST by treatment [4.6 yrs for PCV+RT vs. 4.7 yrs for RT, HR 0.79, 95% CI (0.60, 1.04), P = 0.1]. However, patients with 1p/19q co-deleted tumors lived much longer after PCV+RT (n = 59) than after RT (n = 67) [14.7 vs. 7.3 yrs, HR 0.59, 95% CI (0.37, 0.95), P = 0.03]. There was no difference in MST by treatment in pts without the 1p/19q co-deletion [n=137; 2.6 vs. 2.7 yrs, HR 0.85, 95% CI (0.58, 1.23), P = 0.39]. Re-operation rates upon progression were similar between treatment arms in co-deleted pts (43%, PCV+RT vs. 54%, RT) but salvage CT rates were higher in the RT arm [57% vs. 81% (P = 0.04)]. Conclusions: PCV followed by immediate RT was a highly effective therapy for patients with 1p/19q co-deleted AO/AOA. In this setting, 1p/19q co-deletion was both prognostic and predictive, and the early PFS benefit in co-deleted cases was a harbinger of their longer OS. [This work was supported by RTOG grants U10 CA21661 and U10 CA32115, NCCTG grant U10 CA25224, ECOG grants CA17145 and CA21115, SWOG grant CA32102, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI)]

scholarly journals Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032

2021 ◽  
Author(s):  
Alice L. Yu ◽  
Andrew L. Gilman ◽  
M. Fevzi Ozkaynak ◽  
Arlene Naranjo ◽  
Mitchell B. Diccianni ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Iii ◽  
Long Term Follow Up ◽  
Phase Iii Study

Update on overall survival in COLUMBUS: A randomized phase III trial of encorafenib (ENCO) plus binimetinib (BINI) versus vemurafenib (VEM) or ENCO in patients with BRAF V600–mutant melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9512-9512 ◽  
Author(s):  
Gabriella Liszkay ◽  
Helen Gogas ◽  
Mario Mandalà ◽  
ANA Maria Arance Fernandez ◽  
Claus Garbe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Objective Response ◽  
Progression Free Survival ◽  
Mek Inhibitor ◽  
Phase Iii ◽  
Risk Of Death ◽  
Long Term Follow Up ◽  
Landmark Analyses

9512 Background: BRAF/MEK-inhibitor combinations have a central role in the treatment of BRAF V600–mutant melanoma based on demonstrated benefits on progression-free survival (PFS) and overall survival (OS). Because of these meaningful improvements in outcome, mature landmark analyses of PFS and OS, as well as analyses of some prognostic subgroups, require long-term follow-up. Here we report an updated analysis of OS and other endpoints from the COLUMBUS trial. Methods: In Part 1 of COLUMBUS, 577 patients with advanced/metastatic BRAF V600‒mutant melanoma, untreated or progressed after first-line immunotherapy, were randomized 1:1:1 to ENCO 450 mg QD + BINI 45 mg BID (COMBO450) vs VEM 960 mg BID (VEM) or ENCO 300 mg QD (ENCO300). An updated analysis including PFS, OS, objective response rate (ORR), safety and tolerability, and analyses of results by prognostic subgroups including elevated lactate dehydrogenase (LDH) and degree of organ involvement was conducted after an additional 12 months’ follow-up. Results: At data cutoff, there were 116, 113, and 138 deaths in the COMBO450, ENCO300, and VEM treatment arms, respectively. Across arms, median follow-up for OS was 48.6 months (mo), with median OS of 33.6 mo (95% CI, 24.4–39.2) for COMBO450, 23.5 mo (95% CI, 19.6–33.6) for ENCO300, and 16.9 mo (95% CI, 14.0–24.5) for VEM. Compared to VEM, COMBO450 decreased the risk of death by 39% (HR, 0.61 [95% CI, 0.48–0.79). Updated median PFS was COMBO450, 14.9 mo (95% CI, 11.0–20.2), ENCO300, 9.6 mo (95% CI, 7.4–14.8), and VEM, 7.3 mo (95% CI, 5.6–8.2). PFS was longer for COMBO450 vs VEM (HR, 0.52 [95% CI, 0.40–0.67). Landmark OS and PFS results, as well as subgroup analyses and updated safety and tolerability, will be presented. Conclusions: Updated PFS and OS results for COMBO 450 from the COLUMBUS trial continue to represent new benchmarks for combined BRAF/MEK-inhibitor combinations for treatment of BRAF V600‒mutated melanoma. Clinical trial information: NCT01909453.

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