American Society of Clinical Oncology 2016 Annual Meeting, organized by American Society Of Clinical Oncology (ASCO) was be held on Jun 3 -7, 2016 at McCormick Place, Chicago, Illinois, USA. The Annual Meeting is designed for U.S. and international physicians, researchers and healthcare professionals involved in multidisciplinary clinical cancer care including medical, surgical, and radiation oncologists; pathologists; radiologists; translational-oriented laboratory scientists, nurses, pharmacists, physician assistants, patient advocates and other health care professionals involved in clinical cancer care and cancer research. The theme this year was “Collective wisdom: The future of patient-centered care and research” emphasizing the need to combine knowledge from various disciplines, cancer types, treatment approaches, and big data technologies in order to make progress. There were more than 5000 meeting abstracts with more than 30,000 attendees from all over the world. Below is a brief selection of highlights from some of the neuro-oncology oral and poster presentations at the meeting.
Please note: Information contained in this summary is not intended as medical advice nor does it imply NBTS’ endorsement of any clinical trial, product or company.
Oral Presentations Spotlight
Interim results from a phase III trial on concurrent and adjuvant TMZ chemotherapy in newly diagnosed non-1p19q codeleted anaplastic glioma. CATNON intergroup trial (EORTC 26053-22054) – presented by Martin Van Den Bent MD (Erasmus MC–Daniel den Hoed Cancer Center, Rotterdam, The Netherlands)
This trial was designed to determine if temozolomide (TMZ) provides clinical benefit to non-codeleted 1p19q grade III glioma patients stratified by MGMT status
Two questions are being asked in this trial:
- Would TMZ when given concurrently with radiotherapy (RT) provide better outcome than for RT alone?
- Would adjuvant treatment with TMZ (after chemoRT or RT) be better than non-adjuvant treatment ?
Between December 2007 and September 2015, the trial accrued 751 patients who were randomized into four groups:
- RT alone
- RT/TMZ (concurrent)
- RT then TMZ (adjuvant)
- RT/TMZ then TMZ (adjuvant)
The primary endpoint is overall survival (OS) with secondary endpoints of progression free survival (PFS) and safety.
An interim analysis of the trial data with 745 patients was conducted in the summer of 2015 with recommendations from the Data Safety Monitoring Board (DSMB) to publish results on all endpoints for the adjuvant TMZ comparison part of the trial – without delay – but to continue to follow up for the concurrent TMZ question.
Toxicity was as anticipated based on prior experience with TMZ in patients. The OS results for the adjuvant arms showed that in the no adjuvant RT only group, median OS was 41.1 months whereas in the TMZ adjuvant treated group the median OS was not yet reached, hazard ratio (HR) of 0.67 [95% confidence interval CI: 0.51-0.88; P value = 0.003). For PFS, a median value of 19.0 months was determined in the RT only group versus 42.8 months in the RT plus adjuvant TMZ group (HR 0.62; 95% CI: 0.5-0.76; P value <0.001). At five years, 44% of patients were alive in the RT group compared to 56% in the RT plus adjuvant TMZ group (HR=0.645; 99% CI: 0.45-0.926).
Taken together the results indicate that this is the first trial to show that adjuvant TMZ improves outcome in 1p/19q non-codeleted grade III anaplastic glioma and there is a reasonable assumption that the benefit of adjuvant TMZ will also apply to grade II non 1p19q codeleted glioma patients.
The trial is scheduled to reach a conclusion in 2024 and during the remaining part of the trial, results will be generated to determine whether concurrent RT and TMZ provide superior clinical outcomes over non-concurrent TMZ treatment. Analyses of the effect of MGMT promoter methylation and IDH mutation status on clinical outcomes for patients are also planned. A second interim analysis has been proposed in 2017 or 2018.
A phase III randomized controlled trial of short-course radiotherapy (RT) with or without concomitant and adjuvant temozolomide (TMZ) in elderly patients with glioblastoma (CCTG CE.6, EORTC 26062-22061, TROG 08.02, NCT00482677) – presented by James R Perry MD, FRCPC (Sunnybrook Health Sciences Centre, Toronto, ON, Canada)
At the plenary session on Sunday June 5th, Dr James Perry presented the results of a trial on TMZ treatment in elderly patients. The benefit of RT and TMZ is not clear in patients over 65 with unresolved questions around whether the addition of concurrent and adjuvant TMZ confer a survival advantage in patients receiving standard hypofractionated short course RT. The trial involved 562 patients with a median age of 73 years who were treated with either RT or RT and TMZ (concurrently) and then 12 cycles of adjuvant TMZ.
The results were impressive. The RT and TMZ arm demonstrated significantly improved survival, with a median OS of 9.3 months compared with 7.6 months in the RT-alone arm, and a HR of 0.67 (95% CI 0.56, 0.80; P < 0.0001). The addition of TMZ also yielded prolonged PFS rates, at 5.3 months compared with 3.9 months in the RT-alone arm with a HR of 0.50 (95% CI 0.41, 0.60; p < 0.0001). The 1-year survival rate was 37.8% with TMZ and 22.2% without TMZ; at 2 years, these rates were 10.4% and 2.8%, respectively.
In patients whose tumor had MGMT promoter methylation, the improvement with TMZ was even greater, with a median OS of 13.5 months compared with 7.7 months in patients treated with RT alone, yielding an HR of 0.53 (95% CI: 0.38, 0.73; P = 0.0001). There was also some indication of clinical benefit seen in patients whose tumor did not have MGMT promoter methylation. In those patients, the OS for those who received TMZ was 10.0 months compared with 7.9 months with RT alone, with a HR of 0.75 (95% CI: 0.56, 1.01; P = 0.055).
The conclusions of the study are that in newly diagnosed GBM patients hypofractionated radiation (40Gy in 3 weeks) with both concurrent and adjuvant TMZ is superior to RT without TMZ and is particularly beneficial for MGMT promoter methylated patients. Moreover, the treatments can be undertaken without impact on quality of life and have acceptable toxicity.
It was pointed out that although it is 11 years since the Stupp protocol showing the benefit of RT and TMZ for treating newly diagnosed GBM patients was published and accepted as standard of care, we still haven’t confirmed and optimized the critical components of the treatment paradigm to guide minimum requirements of therapy. If the concurrent RT/TMZ- treatment could be reduced from 6 to 3 weeks (as was undertaken in this study in elderly patients), undesirable effects such as lymphopenia could be much reduced and would help in allowing immunotherapy approaches to work better.
Safety and activity of nivolumab monotherapy and nivo in combination with ipilimumab in recurrent glioblastoma (GBM): Updated results from checkmate-143 presented by David A Reardon, MD, (Dana Farber Cancer Center, Boston, MA)
In this phase I study, groups of GBM patients were dosed with immune checkpoint inhibitor antibodies nivolomab (nivo) and ipilimumab (ipi). Three dose groups were included: a) nivo (3mg/kg) alone; b) nivo (1mg/kg) plus ipi (3mg/kg) and c) nivo (3mg/kg) plus ipi (1mg/kg) followed by nivo (3mg/kg) alone with treatment until confirmed progression or study discontinuation for any reason.
The results indicate that the treatment-related adverse events (AE’s) and treatment-related serious AE’s observed were as expected based on previous studies with these checkpoint inhibitors in trials for other tumor types. Nivo alone was the best tolerated as more toxicities were apparent in the patients administered the combination of nivo and ipi antibodies.
Based on imaging, stable disease or better was achieved in 6/10, 4/10 and 9/20 patients receiving nivo (3mk/kg) alone, nivo (1mg/kg) plus ipi (3mg/kg), and nivo (3mg/kg) plus ipi (1mg/kg) followed by nivo (3mg/kg) respectively. The 12 month OS was 40% (95% CI: 12-67) for Nivo, 30% (CI: 7-58) for nivo (1mg/kg) plus ipi (3mg/kg) and 25% (95% CI: 8-48) nivo (3mg/kg) plus ipi (1mg/kg). These initial findings are encouraging and studies are ongoing with nivo (3mg/kg) to investigate efficacy as well as explore the relationship between potential biomarkers and response .
Other Trials Presented (with links to abstract)
- Encouraging survival with Toca 511 and Toca FC compared to external lomustine control. http://meetinglibrary.asco.org/content/164648-176
- Phase 2 study of aldoxorubicin in relapsed glioblastoma. http://meetinglibrary.asco.org/content/164307-176
- Efficacy of a novel antibody-drug conjugate (ADC), ABT-414, as monotherapy in epidermal growth factor receptor (EGFR) amplified, recurrent glioblastoma (GBM). http://meetinglibrary.asco.org/content/164268-176
- Phase I/II study of S49076, a multi-target inhibitor of c-MET, AXL, FGFR in combination with bevacizumab in patients with recurrent glioblastoma. http://meetinglibrary.asco.org/content/165475-176
- A phase 2 trial of TRC105 with bevacizumab for bevacizumab refractory glioblastoma. http://meetinglibrary.asco.org/content/165607-176
- Phase 1, multicenter, open-label, dose-escalation, study of marizomib (MRZ) and bevacizumab (BEV) in WHO grade IV malignant glioma (G4 MG). http://meetinglibrary.asco.org/content/165643-176
- Randomized phase II study of axitinib alone or combined with lomustine in patients with recurrent glioblastoma. http://meetinglibrary.asco.org/content/166833-176
- Safety and antitumor activity of hypofractionated stereotactic irradiation (HFSRT) with pembrolizumab (Pembro) and bevacizumab (Bev) in patients (pts) with recurrent high grade gliomas: Preliminary results from phase study. http://meetinglibrary.asco.org/content/170205-176
- Safety, efficacy and survival of patients (pts) with primary CNS tumors in phase 1 (Ph1) trials: A 12-year single institution experience. http://meetinglibrary.asco.org/content/167321-176
- Phase I study of single agent ibrutinib in recurrent/refractory primary (PCNSL) and secondary CNS lymphoma (SCNSL) http://meetinglibrary.asco.org/content/167957-176
- Phase 1/2 trial of bevacizumab plus TPI 287, a brain penetrable anti-microtubule agent, in patients with recurrent glioblastoma. http://meetinglibrary.asco.org/content/169232-176
- Phase IB trial of carboxyamidotriazole orotate (CTO) and radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in newly diagnosed glioblastoma (GBM). http://meetinglibrary.asco.org/content/170853-176
- Multicenter Phase IB trial of carboxyamidotriazole orotate (CTO) combined with temozolomide (TMZ) for recurrent glioblastoma (GBM) and other malignant gliomas (MG). http://meetinglibrary.asco.org/content/170853-176
- Patient survival on the dose escalation phase of the Oncolytic Polio/Rhinovirus Recombinant (PVSRIPO) against WHO grade IV malignant glioma (MG) clinical trial compared to historical controls. http://meetinglibrary.asco.org/content/170205-176
- Phase I/II study of VAL-083 in patients with recurrent glioblastoma. http://meetinglibrary.asco.org/content/170752-176
- A phase I study of chemo-radiotherapy with plerixafor for newly diagnosed glioblastoma (GB). http://meetinglibrary.asco.org/content/171457-176
- Ofranogene obadenovec (VB-111), an anti-cancer gene therapy in combination with bevacizumab to improve overall survival compared to bevacizumab monotherapy in patients with rGBM: A phase 2 historically controlled trial. http://meetinglibrary.asco.org/content/167566-176
- Single fraction stereotactic radiosurgery (SRS) alone versus surgical resection and SRS boost for large brain metastases: A multi-institutional analysis. http://meetinglibrary.asco.org/content/169718-176
- Dose-finding study of vinblastine in combination with nilotinib in children, adolescents and young adults with refractory or recurrent low-grade glioma: Results of the ITCC/SIOPE-Brain VINILO phase I trial (NCT01887522). http://meetinglibrary.asco.org/content/167010-176
- Residual tumor volume and change in tumor volume during adjuvant therapy to predict long-term survival in AVAglio: Phase 3 newly diagnosed glioblastoma patients treated with radiation, temozolomide, and bevacizumab or placebo http://meetinglibrary.asco.org/content/170244-176
On Monday June 6th, Vice President Joe Biden addressed a packed ASCO convention center hall to talk about the White House’s Cancer Moonshot Initiative to accelerate cancer research efforts and break down barriers to progress by promoting data sharing and facilitating collaborations to advance cancer prevention, treatment, and care. To watch a recording of the presentation click on this link: http://am.asco.org/virtual-meeting-on-demand/presentation/biden-info