Chemoradiation improves OS, PFS in older patients with glioblastoma
CHICAGO — The addition of concomitant and adjuvant temozolomide to hyperfractionated radiation therapy significantly improved PFS and OS among older patients with newly diagnosed glioblastoma, according to phase 3 study results presented during the plenary session of the ASCO Annual Meeting.
Patients with MGMT–methylated tumors derived the greatest benefit from temozolomide (Temodar, Merck), results showed.
Although glioblastoma occurs primarily in older adults, no clear guidelines for treatment have been defined.
“The peak age of incidence of glioblastoma is 64 years, and the incidence appears to be increasing with our aging population,” James R. Perry, MD, FRCPC, Crolla Family endowed chair in brain tumor research at the Odette Cancer and Sunnybrook Health Sciences Centres in Toronto, said during a press conference. “The current best practice is surgical resection, followed by radiotherapy combined with chemotherapy.”
A recent trial conducted by the EORTC suggested a survival benefit could be gained through the addition of temozolomide to radiation therapy in newly diagnosed patients; however, the researchers observed a trend of decreasing benefit with increasing age, and the potential OS benefit of the combination in older patients remained unknown.
“The studies that we have in older patients over 65 years have only compared radiation schedules head-to-head, or radiation alone vs. temozolomide alone,” Perry said. “There has never been a trial of combined chemotherapy with radiation in elderly patients.”
Perry and colleagues conducted a global randomized clinical trial of 562 older patients (median age, 73 years; range, 65-90; 61% men), whom they randomly assigned to 40 Gy radiation therapy in 15 fractions, with or without 3 weeks of concomitant temozolomide and monthly adjuvant temozolomide (n = 281 for both).
Patients assigned adjuvant temozolomide received treatment for up to 12 cycles or until progression.
Patients assigned temozolomide achieved a median OS of 9.3 months, compared with 7.6 months for patients assigned radiation alone (HR = 0.67; 95% CI, 0.56-0.8). Similarly, the combination arm had a median PFS of 5.3 months, compared with 3.9 months for radiation alone (HR = 0.5; 95% CI, 0.41-0.6).
A total of 462 patients provided an adequate tissue sample for MGMT analysis, which has been conducted in 354 patients to date. Patients with MGMT–methylated tumors (n = 165) assigned temozolomide had a median OS of 13.5 months, compared with 7.7 months for those assigned radiation alone (HR = 0.53; 95% CI, 0.38-0.73).
Unmethylated patients assigned the combination had a median OS of 10 months, compared with 7.9 months in patients assigned radiation (HR = 0.75; 95% CI, 0.56-1.01).
A quality-of-life analysis showed no differences in physical, cognitive, emotional or social functioning between arms. Patients assigned temozolomide reported more nausea, vomiting and constipation than those assigned to radiation alone.
The researcher reported high patient adherence to therapy, with more than 97% of patients able to complete 3 weeks of chemoradiation.
“This is quite important, because the elderly often have difficulties with mobility, or with distance from treatment centers,” Perry said. “They sometimes don’t have a caregiver who is able to bring them back and forth to treatment, so the shorter radiation schedule is an advantage.”
Thirty-nine percent of patients assigned temozolomide and 41% of patients assigned radiation alone received systemic therapy after progression.
“Oncologists now have evidence to consider radiotherapy with temozolomide in all newly diagnosed elderly patients with glioblastoma,” Perry said. – by Cameron Kelsall
Perry JR, et al. Abstract LBA2. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: This study received funding from the Canadian Cancer Society Research Institute and through an unrestricted grant from Schering-Plough/Merck. Perry reports stock and ownership interests in DelMar Pharmaceuticals and VBL Therapeutics. Please see the abstract for a list of all other researchers’ relevant financial disclosures.