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Aim: We aimed to identify SNPs associated with cabazitaxel toxicity and response within a Phase II clinical trial using this compound in advanced transitional cell carcinoma after progression to a platinum-based regimen. Patients & methods: Eleven SNPs in CYP3A4, CYP3A5, CYP2C8, ABCB1 and TUBB1 were genotyped in 45 patients. Results: CYP3A5 rs776746 A allele was associated with protection against gastrointestinal toxicity (odds ratio: 0.06, 95% CI: 0.007–0.63, p = 0.018) and with reduced progression-free survival (hazard ratio: 5.1, 95% CI: 1.7–15.1, p = 0.0038, multivariable analysis). ABCB1 SNPs were associated with total number of grade 3–4 toxicity events (p-values of 0.009, 0.041 and 0.043, respectively). Conclusion: Polymorphisms in CYP3A5 and ABCB1 may define a subset of patients with different cabazitaxel toxicity and efficacy and therefore could be used as markers for treatment optimization.

High incidence and prognostic relevance of thromboembolic disease in patients with ALK-rearranged NSCLCs

e13608Background: The Spanish Lung Cancer Group (GECP) initiated a Tumor Thoracic Register (RTT) in September 2016 with the aim of evaluating accurate, basic data concerning this oncological pathol...

Background Context Spinal instability is an acknowledged complication of spinal metastases; in spite of recent suggested criteria, it is not clearly defined in the literature. Purpose This study aimed to assess intra and interobserver agreement when using the Spine Instability Neoplastic Score (SINS) by all physicians involved in its management. Study Design Independent multicenter reliability study for the recently created SINS, undertaken with a panel of medical oncologists, neurosurgeons, radiologists, orthopedic surgeons, and radiation oncologists, was carried out. Patient Sample Ninety patients with biopsy-proven spinal metastases and magnetic resonance imaging, reviewed at the multidisciplinary tumor board of our institution, were included. Outcome Measures Intraclass correlation coefficient (ICC) was used for SINS score agreement. Fleiss kappa statistic was used to assess agreement on the location of the most affected vertebral level; agreement on the SINS category ("stable," "potentially stable," or "unstable"); and overall agreement with the classification established by tumor board. Methods Clinical data and imaging were provided to 83 specialists in 44 hospitals across 14 Spanish regions. No assessment criteria were pre-established. Each clinician assessed the SINS score twice, with a minimum 6-week interval. Clinicians were blinded to assessments made by other specialists and to their own previous assessment. Subgroup analyses were performed by clinicians' specialty, experience (≤7, 8–13, ≥14 years), and hospital category (four levels according to size and complexity). This study was supported by Kovacs Foundation. Results Intra and interobserver agreement on the location of the most affected levels was "almost perfect" (κ>0.94). Intra-observer agreement on the SINS score was "excellent" (ICC=0.77), whereas interobserver agreement was "moderate" (ICC=0.55). Intra-observer agreement in SINS category was "substantial" (k=0.61), whereas interobserver agreement was "moderate" (k=0.42). Overall agreement with the tumor board classification was "substantial" (κ=0.61). Results were similar across specialties, years of experience, and hospital category. Conclusions Agreement on the assessment of metastatic spine instability is moderate. The SINS can help improve communication among clinicians in oncology care.

PURPOSE: To assess variability in the use of Tomita and modified Bauer scores in spine metastases. MATERIALS AND METHODS: Clinical data and imaging from 90 patients with biopsy-proven spinal metastases, were provided to 83 specialists from 44 hospitals. Spinal levels involved and the Tomita and modified Bauer scores for each case were determined twice by each clinician, with a minimum of 6-week interval. Clinicians were blinded to every evaluation. Kappa statistic was used to assess intra and inter-observer agreement. Subgroup analyses were performed according to clinicians' specialty (medical oncology, neurosurgery, radiology, orthopedic surgery and radiation oncology), years of experience (⩽7, 8-13, ⩾14), and type of hospital (four levels). RESULTS: For metastases identification, intra-observer agreement was "substantial" (0.600.80) at the other levels. Inter-observer agreement was "almost perfect" at lumbar spine, and "substantial" at the other levels. Intra-observer agreement for the Tomita and Bauer scores was almost perfect. Inter-observer agreement was almost perfect for the Tomita score and substantial for the Bauer one. Results were similar across specialties, years of experience and type of hospital. CONCLUSION: Agreement in the assessment of metastatic spine disease is high. These scoring systems can improve communication among clinicians involved in oncology care., This study was funded by the Kovacs Foundation, a not-for-profit Spanish institution specializing in neck and back pain research, and with no links to the health industry.

e15537 Background: No standard regimen exists for second line treatment of mTCC patients. Taxanes have shown some activity in this setting. Cbz, is a novel semi-synthetic taxane never tested before...

4525 Background: Treatment of mTCC progressing to cisplatin is an unmet need. Prognostic factors (PF) for worse overall survival (OS) are ECOG >0, Hb

Aim: Cabazitaxel (Cab) is a novel tubulin-binding taxane active in preclinical models against docetaxel-sensitive and resistant tumors. Cab is approved for the treatment of metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure; however, its activity against other cancers remains unexplored. SOGUG 2011-04 is a phase II clinical trial designed to explore the efficacy of Cab in advanced genitourinary TCC after progression to a platinum-based regime. As part of this trial, a pharmacogenetic study to identify single-nucleotide polymorphisms (SNPs) predictive of Cab toxicity and response was conducted. Methods: DNA was extracted from blood samples from 45 patients in this trial. Nine key SNPs in genes involved in the pharmacokinetic and pharmacodynamic pathways of Cab (CYP3A4 rs35599367; CYP3A5 rs776746; CYP2C8 rs11572080 and rs1113129 ABCB1 rs1045642, rs1128503 and rs2032582; TUBB1 rs6070697 and rs463312) were genotyped using standard techniques. Logistic regression was used to study toxicity and response, and Cox regression to analyze progression free survival (PFS) and overall survival (OS), using an additive genetic model. Preliminary results are presented. Results: CYP3A5 rs776746 (splicing defect) protected against gastrointestinal (GI) toxicity (OR = 0.06, 95%CI = 0.007-0.63, P = 0.018) and was associated with reduced PFS (HR = 4.4, 95%CI = 1.6-11.7, P = 0.0032). Adjusting for patient prognosis, according to Bellmunt's classification, did not change the results. Furthermore ABCB1 rs1128503, rs1045642 and rs2032582 were associated with the total number of Grade 3-4 toxicity events (P values of 0.009, 0.041, and 0.043, respectively, multivariable analysis). TUBB1 Q43P missense polymorphism was associated with reduced OS (P = 0.0023) although only three patients carried this variant. Conclusions: Polymorphisms in CYP3A5 may define a subset of patients with decreased Cab activity resulting in less GI adverse events and shorter PFS. Additionally, variation in ABCB1 may be associated with the severity of Cab toxicity. These results need to be validated in larger and independent series but suggest potential markers for Cab treatment optimization. * This study has been supported by an unrestricted educational grant of Sanofi-Aventis to the Spanish GU Oncology Group (SOGUG) Disclosure: I. Duran: has participated in compensated Advisory Boards for Sanofi-Aventis; M. Climent: has participated in compensated Advisory Boards for Sanofi-Aventis. All other authors have declared no conflicts of interest.

5581 Background: Cisplatin alone or in combination remains the standard for recurrent/metastatic head and neck carcinoma, however it is associated with significant toxicity. Better toxicity profile...

Purpose The present article reports the results of a multicentre phase II study analysing both activity and tolerance of the cisplatin vinorelbine combination in patients with inoperable NSCLC.