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Randomized Controlled Trial
. 2014 Mar 10;32(8):783-90.
doi: 10.1200/JCO.2013.49.3726. Epub 2014 Feb 10.

Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH

J Gregory Cairncross  1 , Meihua Wang, Robert B Jenkins, Edward G Shaw, Caterina Giannini, David G Brachman, Jan C Buckner, Karen L Fink, Luis Souhami, Normand J Laperriere, Jason T Huse, Minesh P Mehta, Walter J Curran Jr
Affiliations
Randomized Controlled Trial

Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH

J Gregory Cairncross et al. J Clin Oncol. .

Abstract

Purpose: Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT.

Patients and methods: Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT.

Results: IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT.

Conclusion: IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.
Fig 1.
Kaplan-Meier estimates of overall survival (OS) by treatment (procarbazine, lomustine, and vincristine [PCV] plus radiotherapy [RT] or RT) for patients with (A) IDH-mutated and (B) nonmutated tumors. Hazard ratio (HR) ratio for OS for those with mutated tumors was 0.59 (95% CI, 0.40 to 0.86; P = .006); HR for those with nonmutated tumors was 1.14 (95% CI, 0.63 to 2.04; P = .67).
Fig 2.
Fig 2.
Kaplan-Meier estimates of overall survival for patients whose tumors were IDH mutated and 1p/19q codeleted (co-del; gold), mutated (mut) and noncodeleted (blue), and nonmutated and noncodeleted (gray) after (A) procarbazine, lomustine, and vincristine (PCV) plus radiotherapy (RT) and (B) RT alone. Median survivals after (A) PCV plus RT were 14.7 (95% CI, 6.4 to not reached), 5.5 (95% CI, 2.6 to 11.0), and 1.0 years (95% CI, 0.6 to 1.9; P < .001), respectively. Median survivals after (B) RT alone were 6.8 (95% CI, 5.4 to 8.6), 3.3 (95% CI, 2.5 to 4.9), and 1.3 years (95% CI, 0.8 to 1.9; P < .001), respectively.
Fig 3.
Fig 3.
Kaplan-Meier estimates of overall survival (OS) by treatment (procarbazine, lomustine, and vincristine [PCV] plus radiotherapy [RT] or RT) for those with (A) IDH mutated and 1p/19q codeleted and (B) IDH mutated noncodeleted tumors. Hazard ratio (HR) for OS for those with (A) mutated codeleted tumors was 0.49 (95% CI, 0.28 to 0.85; P = .01); HR for those with (B) mutated noncodeleted tumors was 0.56 (95% CI, 0.32 to 0.99; P = .05).
Fig 4.
Fig 4.
Kaplan-Meier estimates of (A) progression-free survival (PFS) and (B) overall survival (OS) by treatment (procarbazine, lomustine, and vincristine [PCV] plus radiotherapy [RT] or RT) for G allele carriers. Hazard ratio (HR) for (A) PFS was 0.42 (95% CI, 0.24 to 0.71; P = .001); HR for (B) OS was 0.65 (95% CI, 0.36 to 1.16; P = .14).
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