Gustavo Rubio

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study

Background:Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA).Methods:This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (β-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded.Results:Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with β-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression.Conclusion:In patients with PCa and bone metastases treated with ZA, β-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Gemcitabine and Carboplatin for Patients With Advanced Non-Small Cell Lung Cancer

The survival of patients with advanced non-small cell lung cancer remains poor. Cisplatin-based chemotherapy produces a modest benefit in survival compared with that observed with best supportive care. Gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN), a novel nucleoside antimetabolite, is active and well tolerated. The combination of gemcitabine/cisplatin has shown a significant improvement in response rate and survival over cisplatin alone. Phase III trials comparing gemcitabine/cisplatin with older combinations such as cisplatin/etoposide or mitomycin/ifosfamide/cisplatin have shown a higher activity for gemcitabine/cisplatin; however, the best way to combine these drugs remains unclear. In addition, the 3-week schedule has obtained a higher dose intensity with less toxicity and similar efficacy as the 4-week schedule. The role of carboplatin in combination with new drugs is still under evaluation. Gemcitabine/carboplatin seems to be a good alternative, with the advantage of ambulatory administration and lower nonhematologic toxicity. The 4-week schedule has produced frequent grade 3/4 neutropenia and thrombocytopenia in some studies. The 3-week schedule, using gemcitabine on days 1 and 8 and carboplatin on day 1, is a convenient and well-tolerated regimen. The toxicity profile is acceptable without serious symptoms. This schedule could be considered a good option as a standard regimen. Semin Oncol 28 (suppl 10):4-9.

A randomized phase II/III study of cabazitaxel versus vinflunine in metastatic or locally advanced transitional cell carcinoma of the urothelium (SECAVIN)

Background Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine. Patients and methods This is a multicenter, randomized, open-label, phase II/III study, following a Simons optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III. Results Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7-32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9-54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9 months for vinflunine (P = 0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5 months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms. Conclusion This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously. Trial number NCT01830231.

849PREAL LIFE EFFICACY AND SAFETY OF AXITINIB (AXI) IN PATIENTS WITH RENAL CELL CARCINOMA (RCC): RESULTS FROM THE SPANISH COMPASSIONATE USE PROGRAM

ABSTRACT Aim: AXI is a vascular endothelial growth factor receptor tyrosin kinase inhibitor recently approved for the treatment of patients (pts) with RCC after failure of sunitinib or a cytokine. In a phase III study, AXI showed an improved progression free survival (PFS) compared to sorafenib after failure to one prior treatment. Methods: A retrospective data collection of pts treated under the Spanish compassionate use program was carried out. The objective of the study was to analyze the efficacy and safety of AXI in the real life setting. The study was approved by the regulatory authorities. Results: From September 2011 to March 2014, a total of 225 pts from 45 centers were included, 73.3% were male and the median age was 55 years (range 29-86). 80% had clear cell RCC and 88.4% had prior nephrectomy. 47.6% received AXI in 2nd line, 29.8% in 3rd line and 24.7% in 4th or subsequent line. The starting dose was 5 mg/12h in 97.3% of pts, 13.1% had at least one dose titration and 16.4% a dose reduction, mainly due to toxicity. At present, 30.8% of the pts continue on treatment with AXI. The response rate (RR) was 24% with 41.5% of disease stabilization (SD). Median PFS for all pts was 4.86 months (95%CI 3.92-5.81). Median PFS for pts that received AXI in 2nd, 3rd, or 4th or further line was 3.45, 5.03 and 5.49 months respectively (p= 0.383). Patients that achieved a response had a longer PFS than those who achieved only SD with a PFS of 12.32 and 7.00 months respectively (p = 0.009). PFS was also analyzed for several patient subgroups: Patient subgroup PFS (months) p value Clear cell vs. non-clear cell 4.93 vs. 3.88 0.098 Prior nephrectomy vs. no nephrectomy 5.03 vs. 2.69 0.106 Age 5.03 vs. 3.45 0.322 PS 0-1 vs. PS ≥2 5.68 vs. 2.56 No or mild renal impairment vs. moderate or severe renal impairment 4.60 vs. 4.90 0.484 Median overall survival (OS) for all pts was 9.63 months. 76.9% of pts developed at least one adverse event (AE). Most common AE were, all grades (grade 3-4): asthenia 52% (9.3%), diarrhea 30.6%(4.8%) and hypertension 30.1% (2.2%). Conclusions: The overall PFS is similar to the one reported in the phase III trial in patients previously treated with sunitinib. These data confirm the efficacy and safety of AXI in an unselected population. Disclosure: All authors have declared no conflicts of interest.

Results of the FLAC European Database of Metastatic Castration-Resistant Prostate Cancer Patients Treated With Docetaxel, Cabazitaxel, and Androgen Receptor-Targeted Agents

Micro‐Abstract Several agents have demonstrated an overall survival (OS) benefit in metastatic castration‐resistant prostate cancer (mCRPC); however, optimal sequencing is unknown. Retrospective analysis of data from 574 mCRPC patients showed increasing OS with the number of therapies provided; a sequence including docetaxel, cabazitaxel (CABA), and an androgen receptor–targeted agent (ART) provided the greatest benefit. Prior administration of ART did not appear to influence CABA activity. These findings will help guide treatment decisions in daily practice. Background: Several agents have demonstrated an overall survival (OS) benefit in patients with metastatic castration‐resistant prostate cancer (mCRPC); however, the optimal sequencing of these therapies is unknown as a result of a lack of prospective randomized controlled trials. This retrospective study aimed to identify clinical factors influencing outcomes and to determine optimal treatment sequencing in patients with mCRPC treated with cabazitaxel (CABA) and/or androgen receptor–targeted agents (ART) after androgen‐deprivation therapy (ADT) and docetaxel (DOC). Patients and Methods: Records of 574 consecutive patients treated (2012−2016) at 44 centers in 6 countries were retrospectively examined. Results: A total of 267 patients received ADT → DOC → CABA (group 1), 183 patients ADT → DOC → ART → CABA (group 2), and 124 patients ADT → DOC → CABA → ART (group 3), with respective median OS from diagnosis of mCRPC of 38.3, 44.45, and 53.9 months (P = .012 for group 3 vs. group 1). Multivariate analysis showed response to first ADT ≤ 12 months, Gleason score of 8 to 10, clinical progression, and high prostate‐specific antigen levels at mCRPC diagnosis were associated with worse OS. Prior receipt of ART did not influence activity of CABA. Conclusion: OS appeared to increase with the number of life‐extending therapies, with a sequence including DOC, CABA, and an ART providing the greatest OS benefit.

Predictors for survival with cabazitaxel (CBZ) in metastatic, castration-resistant prostate cancer (mCRPC): Long term follow-up of the Spanish registry.

e602Background: The clinical experience with CBZ in mCRPC patients (pts) has enriched notably since its approval for clinical use, but there is still a lack of well-defined prognostic/predictive factors to better characterize the profile of pts that could achieve the best therapeutic benefit. Analysis of the final expanded cohort and mature long-term follow-up are presented. Methods: Medical records from mCRPC pts progressing during or after docetaxel and treated with CBZ at 21 centres in Spain were reviewed retrospectively. Baseline characteristics, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Univariate and multivariate analysis of a variety of factors predicting OS were conducted. Results: 187 consecutive pts (median age 69) with intermediate-poor prognostic baseline characteristics (Table 1) received a median of 6 cycles (range 2-59) of CBZ. Median OS from first CBZ cycle was 15.3 [CI: 11.7; 18.0] months (mo) and median clinical and/or rPFS was 7.9...

2638 Effectiveness of 2nd-line and subsequent therapies after pazopanib (Paz) in patients (pt) with metastatic renal cell carcinoma (mRCC): Final results of the SPAZO study (SOGUG)

J.A. Arranz Arija, B. Perez-Valderrama, J.L. Gonzalez-Larriba, A. Rodriguez Sanchez, I. Chirivella, A. Pinto, R.D. Garcia Marrero, G. Rubio, J.M. Jurado Garcia, P. Borrega, M. Lazaro Quintela, D.E. Castellano, C. Suarez Rodriguez, J.A. Meana Garcia, J.J. Lambea-Sorrosal, P. Gajate, M.J. Juan Fita, J.L. Puertas, R. Garcia Dominguez, J.C. Villa Guzman. Hospital General universitario Gregorio Maranon, Medical Oncology Service, Madrid, Spain; Hospitales Universitarios Virgen del Rocio, Medical Oncology Service, Seville, Spain; Hospital Clinico San Carlos, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Leon, Medical Oncology Service, Leon, Spain; Hospital Clinico Universitario, Medical oncology Service, Valencia, Spain; Hospital Universitario La Paz, Medical Oncology Service, Madrid, Spain; Hospital Universitario de Canarias, Medical Oncology Service, Santa Cruz de Tenerife, Spain; Hospital Universitario Fundacion Jimenez Diaz, Medical Oncology Service, Madrid, Spain; Hospital Universitario San Cecilio, Medical Oncology Service, Granada, Spain; Hospital San Pedro de Alcantara, Medical Oncology Service, Caceres, Spain; Complexo Hospitalario Universitario de Vigo, Medical Oncology Service, Vigo, Spain; Hospital Universitario 12 de Octubre, Medical Oncology Service, Madrid, Spain; Hospital Universitari Vall d’Hebron, Medical Oncology Service, Barcelona, Spain; Hospital General Universitario de Alicante, Medical Oncology Service, Alicante, Spain; Hospital Universitario Lozano Blesa, Medical Oncology Service, Zaragoza, Spain; Hospital Universitario Quiron, Medical Oncology Service, Madrid, Spain; 17 Instituto Valenciano de Oncologia IVO, Medical Oncology Service, Valencia, Spain; Hospital Universitario Rio Hortega, Medical Oncology Service, Valladolid, Spain; Hospital Universitario de Salamanca, Medical Oncology Service, Salamanca, Spain; Hospital General Universitario de Ciudad Real, Medical Oncology Service, Ciudad Real, Spain