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2038 Background: The pRB-dependent cell cycle checkpoint is altered in the vast majority of anaplastic oligodendrogliomas (AO), either by homozygous deletion or by hypermethylation of CDKN2A and/or CDKN2B, or by amplification and/or overexpression of CDK4. Palbociclib is an oral inhibitor of CDK4 and 6 that has already been shown to be highly active in breast cancer. Methods: We conducted a multicenter, open-label, phase II trial evaluating efficacy and safety of Palbociclib in patients with AO that progressed to radiotherapy and more than one chemotherapy regimen containing Temozolomide and/or Lomustine. Inclusion criteria included: histologically and molecularly confirmed grade III oligodendroglioma (WHO 2016 classification, IDH1/2 mutation and 1p/19 codeletion were mandatory), recurrence after radiotherapy and 1 or 2 chemotherapy regimens and conserved RB protein expression by immunohistochemistry (IHC). Patients were treated with Palbociclib 125 mg/daily 3 weeks on/1off. The primary objective of the study was progression-free survival at 6 months (6M-PFS). Results: Between October 2015 and September 2018, 34 patients were enrolled across ten hospitals. The study was stopped early secondary to lack of efficacy, with 74% of evaluable patients progressing within 6 months. Number of patients alive and free from progression at 6 months after the enrollment was 9 (26%) out of the first 34 patients, below the minimum number required (18 out of 40) to consider Palbociclib as an active drug in this population. With a median follow-up of 11.2 months, the median PFS was 3 months (95% CI: 2.5-3.5 months). Median overall survival (OS) was 23.1 months (95% CI: 17.2-25 months). There were no partial or complete responses and only 11 patients (32%) achieved stable disease as best response. Palbociclib was well tolerated with neutropenia (Grade 3 or 4: 40%) and thrombocytopenia (Grade 3 or 4: 15%) as the most common adverse effects (AEs). Both AEs had no significant impact since there were no episodes of febrile neutropenia or bleeding. Conclusions: Despite the good tolerance and drug exposure, Palbociclib monotherapy did not show favorable activity in recurrent AO. Clinical trial information: NCT02530320.

3082 Background: Identification of “agnostic” genetic drivers in cancer is foreseen as a major step forward in precision medicine.Unfortunately, “off label” use of targeted therapies is not widely available and many oncogenic alteration do not present the same behaviour accross all tumor types.We aimed to analyze the real impact on patients management of the implementation of a systematic screening of genetic alterations in centers of the Spanish Group for Rare Cancer (GETHI). Methods: We designed an observational, prospective and multicenter study to molecularly characterize any adult patient with advanced cancer.Formalin fixed paraffin-embedded samples were studied by TrkA-C,ROS1 and ALK immunohistochemistry followed by RT-PCR when positive to confirm gene fusions. Additonally, the Next Generation Sequencing paltform ArcherFusion Plex (able to detect point mutations and rearrangements in 53 cancer related genes) was implemented.Clinical data regarding treatment administered and outcome, were collected from patients identified as harboring drugable alterations. Results: Up to 26 hospitals all over the country got involved in the study. 341 tumoral tissues, representing 41 different histologies were collected. Molecular studies could be performed in 292 samples that led to the identification of 33 patients as harboring somatic oncogenic mutations. 21 were considered druggable and 5 got targeted therapy directed against the alteration identified (three glioblastoma patients with EGFR mutations received erlotinib, one prostate cancer with a BRAF fusion received trametinib and one lung cancer with ALK translocation, previously deemed as negative by standard screening, received crizotinib). One of the glioblastoma patients achieved a long lasting stabilitation and both the prostate and lung tumors presented dramatic partial responses. Conclusions: Though only few cases harboring drugable alteratons got specif treatment, 50% achieved a meanignful benefit. A wide access to molecular screening and targeted drugs could improve the outcome of cancer patients.

2001 Background: The GEINO-14-01 trial (NCT02209948) investigated the role of extending temozolomide (TMZ) for 6 cycles after the standard 6 cycles to improve 6m-PFS, SLP and OS in newly diagnosed glioblastoma (GBM) patients (p). Methods: Between 08/2014 and 11/2018, 166 p were screened and 159 randomized to extend (80p) or not (79p) TMZ treatment for 6 cycles after proving stable disease in the MRI performed before inclusion. Centralized review of histology and determination of MGMT status, if not previously available, were performed before randomizing patients. Two criteria of stratification were used: MGMT status and presence/absence of residual disease on the basal MRI (defined as a residual enhancement larger than 1cm in one). The primary endpoint was differences in 6mPFS, secondary endpoints were differences in PFS, OS, toxicity, between arms and per stratification factors. Results: Median age was 60.3 (range 29-83), 97p (61%) were methylated, basal MRI showed residual disease in 57p (35.8%). After a median follow up of 14.0 months, with 121 p(76.1%) already progressed and 81p (50.9%) already dead, median PFS is presented. Median (m) PFS is 8.0 months (95%CI: 5.7-10.2). There is no difference in mPFS between arms (adjusted HR = 0.98, 95% CI: 0.82-1.18, P = 0.907). Methylated tumors had longer mPFS (HR=0.57, 95% CI: 0.39-0.83, P=0.004) irrespectively to the study treatment. Conclusions: There is not apparent benefit of continuing TMZ treatment for more than 6 cycles. Data will be actualized for the congress.Supported by a Grant of the ISCIII: PI13/01751. Clinical trial information: NCT02209948.

195 Background: Temozolomide (TMZ) is an alkylating agent that has shown good results in the treatment of neuroendocrine and central nervous system (CNS) tumors. The loss of O-6-methylguanine-DNA methyltransferase (MGMT) expression by pyrosequencing (PSQ) is a predictive factor of response to treatment with TMZ in high-grade gliomas. However, its predictive value in pancreatic neuroendocrine tumors (pNET) is controversial, and there is no consensus on how to best assess MGMT. The aim was to evaluate the objective response rate in pNET according to the state of MGMT, assessed by PSQ for evaluation of promoter methylation and immunohistochemistry (IHC). Methods: Patients with pNET who were treated with TMZ at the center between 2008 and 2017 were studied retrospectively. Ten patients were included in the study. A deficiency of MGMT was determined by IHC and MGMT promoter methylation by PSQ. For IHC, the cut-off was 10%, defined as negative < 10% of tumor cells positive in the tumor tissue. For the PSQ, the cut-off was 8%, defined as methylated who presented > 8%. Results: A deficiency of MGMT was detected in five patients (50%) by IHC. An MGMT promoter methylation by PSQ was observed in three patients (30%). The IHC results were consistent with PSQ results in only six patients (60%); one patient with methylated MGMT had positive IHC, and three patients had unmethylated MGMT by PSQ unmethylated, IHC negative. PSQ had a high positive predictive value of response because the three patients with MGMT promoter methylation by PSQ presented objective responses (OR). Nevertheless, a low negative predictive power (57%) was observed because three of seven patients with unmethylated MGMT presented OR. Of the five patients with MGMT deficiency by IHC, four (80%) presented OR, suggesting positive predictive value of 80%; however, it also presented a low negative predictive power of 60%. Conclusions: Despite having 100% of the patients with MGMT promoter methylation showing OR in this series, the low negative predictive power suggests that the absence of MGMT deficiency by IHC or MGMT unmethylated by PSQ does not contraindicate the use of TMZ in pNET treatment.