19th Society for Neuro-Oncology Annual Meeting
Electric ﬁelds for glioblastoma
Published Online November 21, 2014 http://dx.doi.org/10.1016/ S1470-2045(14)71126-X The 19th annual meeting of the Society for Neuro-Oncology was held in Miami, FL, USA, on Nov 13–16, 2014
The use of the NovoTTF-100A system (NovoTTF) for local delivery of electric ﬁelds to patients with newly diagnosed glioblastoma receiving temozolomide signiﬁcantly improves treatment outcomes compared with temozolomide alone. Presenting data from an international, multicentre randomised phase 3 trial, Roger Stupp (Zurich, Switerland) on behalf of his co-investigators described outcomes from a planned interim analysis of 315 patients randomly assigned to receive either NovoTTF plus temozolomide (n=210) or temozolomide alone (n=105). All patients receive upfront radiotherapy plus temozolomide before 2:1 randomisation to the two treatment groups. Adverse events were similar between the two groups with the exception of skin irritation, which was higher with NovoTTF plus temozolomide. Progressionfree survival, the primary outcome, was 7·1 months in the combination group compared with 4·0 months in the temozolomide alone group (HR 0·63, p=0·001). Overall survival was 19·6 months in the NovoTTF plus temozolomide group versus 16·6 months in the control group (HR 0·75, p=0·034). The data safety monitoring committee have now recommended that the trial is stopped because of the substantial activity in the experimental group.
ALK inhibitors for brain metastases ALK inhibitors for ALK-rearranged non-small-cell lung cancer are now the new standard of care in this disease. However, advanced nonsmall-cell lung cancer often presents with brain metastases. The eﬃcacy of ALK inhibitors in this setting is unknown. Analysing a subset of patients in the ASCEND1 trial, which investigated the secondgeneration ALK inhibitor ceritinib, 18
Ranee Mehra (Philadelphia, PA, USA) and colleagues found 124 patients of the original 246 enrolled had brain metastases at baseline. Median progression-free survival among this group was 6·9 months compared with the 8·2 months reported for the entire cohort in updated data presented at ESMO 2014. Importantly, among 14 patients with measurable brain lesions, seven showed a response in their brain tumour and three had stable disease, thus suggesting that ceritinib can cross the blood–brain barrier and has activity against brain metastases. The trialists also found that previous use of ALK inhibitors did not aﬀect response.
Rindopepimut vaccine for relapsed glioblastoma Results from the randomised ReACT phase 2 trial show bevacizumab plus a vaccine consisting of the EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin, and delivered intradermally with GM-CSF, can elicit signiﬁcant improvements in progression-free survival at 6 months and in overall survival compared with bevacizumab plus placebo. David Reardon (Boston, MA, USA) and colleagues found an objective response rate of 23% among patients treated with bevacizumab plus vaccine versus 12% in patients treated with bevacizumab plus placebo. Of the 115 patients treated, the main adverse event was grade 1–2 reaction at the injection site. Furthermore, Evangelia Razis (Athens, Greece), presenting data from a rindopepimut compassionate use programme for patients not eligible for ongoing trials, showed the vaccine has activity among many types of glioblastoma. A phase 3 trial of rindopepimut will start soon.
phase 2 trial of lapatinib and dosedense temozolomide for adults with recurrent ependymoma. This cancer is rare in adults and there is no standard treatment. 50 patients were enrolled into the study and had a mixture of grades and CNS locations. Median progression-free survival for the entire group was 36 weeks, but this diﬀered by grade and location, with ependymomas of the spinal cord doing best: median progressionfree survival was 96 weeks and 80% of patients were still free from progression at 6 months in this subgroup of patients. Patients with the highest expression of HER2 mRNA seemed to respond best to treatment, and patients only experienced modest myelotoxicity and rash.
Dendritic-cell vaccine active in newly diagnosed glioblastoma
Breast cancer drug active in ependymoma
According to Patrick Wen (Boston, MA, USA) and colleagues, autologous dendritic cells pulsed with six synthetic peptide CTL epitopes targeting the glioblastoma tumour/ stem cell-associated antigens, MAGE-1, HER2, AIM-2, TRP-2, gp100, and IL-13Rα2, followed by maintenance temozolomide, signiﬁcantly improves progression-free survival for patients with newly diagnosed glioblastoma. In this double-blinded, 2:1 randomised, phase 2 trial, 124 patients received either the vaccine or a control formulation for 12 months after standard tumour resection and adjuvant temozolomide and radiation therapy. Median progression-free survival was signiﬁcantly improved in the vaccine group (HR 0·57, p=0·01). There were no major adverse events or eﬀects on quality of life. Patients with HLA-A2 tumours and methylated MGMT seemed to have the best response. A phase 3 trial will soon begin enrolment.
Mark Gilbert (Houston, TX, USA) and fellow researchers have done a
David Collingridge www.thelancet.com/oncology Vol 16 January 2015