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Immune checkpoint inhibitors; Metastatic renal carcinoma; Second-line treatment Inhibidors del punt de control immunitari; Carcinoma renal metastàtic; Tractament de segona línia Inhibidores del punto de control inmunitario; Carcinoma renal metastásico; Tratamiento de segunda línea Background: The INMUNOSUN trial had the objective of prospectively evaluating the efficacy and safety of sunitinib as a pure second-line treatment in patients with metastatic renal cell carcinoma (mRCC) who have progressed to first-line immune checkpoint inhibitor (ICI)-based therapies. Patients and methods: A multicenter, phase II, single-arm, open-label study was carried out in patients with a histologically confirmed diagnosis of mRCC with a clear-cell component who had progressed to a first-line regimen of ICI-based therapies. All patients received sunitinib 50 mg once daily orally for 4 weeks, followed by a 2-week rest period following package insert instructions. The primary outcome was the objective response rate. Results: Twenty-one assessable patients were included in the efficacy and safety analyses. Four patients [19.0%, 95% confidence interval (CI) 2.3% to 35.8%] showed an objective response (OR), and all of them had partial responses. Additionally, 14 (67%) patients showed a stable response, leading to clinical benefit in 18 patients (85.7%, 95% CI 70.7% to 100%). Among the four assessable patients who showed an OR, the median duration of the response was 7.1 months (interquartile range 4.2-12.0 months). The median progression-free survival (PFS) was 5.6 months (95% CI 3.1-8.0 months). The median overall survival (OS) was 23.5 months (95% CI 6.3-40.7 months). Patients who had better antitumor response to first-line ICI-based treatment showed a longer PFS and OS with sunitinib. The most frequent treatment-emergent adverse events were diarrhea (n = 11, 52%), dysgeusia (n = 8, 38%), palmar-plantar erythrodysesthesia (n = 8, 38%), and hypertension (n = 8, 38%). There was 1 patient who exhibited grade 5 pancytopenia, and 11 patients experienced grade 3 adverse events. Eight (38%) patients had serious adverse events, four of which were considered to be related to sunitinib. Conclusion: Although the INMUNOSUN trial did not reach the pre-specified endpoint, it demonstrated that sunitinib is active and can be safely used as a second-line option in patients with mRCC who progress to new standard ICI-based regimens. This work was supported by Pfizer, S.L.U. (Madrid, Spain). Pfizer, S.L.U. provided an unrestricted research grant with drug funding and drug supply to conduct the study (no grant number).

PurposeNearly 40% of the advanced cancer patients will present brain metastases during the course of their disease, with a 2-year life expectancy of less than 10%. Immune system impairment, including the modulation of both STAT3 and PD-L1, is one of the hallmarks of brain metastases. Liquid biopsy could offer several advantages in brain metastases management, such as the possibility of non-invasive dynamic monitoring. Extracellular vesicles (EVs) have been recently proposed as novel biomarkers especially useful in liquid biopsy due to their secretion in biofluids and their role in cell communication during tumor progression.Materials and MethodsThe main aim of this work was to characterize the size and protein cargo of plasma circulating EVs in patients with solid tumors and their correlation with newly diagnosed brain metastases, in addition to their association with other relevant clinical variables.ResultsWe analyzed circulating EVs in the plasma of 123 patients: 42 patients with brain metastases, 50 without brain metastases and 31 healthy controls. Patients with newly diagnosed brain metastases had a lower number of circulating EVs in the plasma and a higher protein concentration in small EVs (sEVs) compared to patients without brain metastases and healthy controls. Interestingly, melanoma patients with brain metastases presented decreased STAT3 activation and increased PD-L1 levels in circulating sEVs compared to patients without central nervous system metastases.ConclusionsDecreased STAT3 activation and increased PD-L1 in plasma circulating sEVs identify melanoma patients with brain metastasis.Statement of translational relevanceBrain metastases are critical for outcomes and quality of life in almost 50% of oncological patients, generally associated with a poor short-term prognosis. Early or preventive diagnosis of this complication represents an unmet need. There is a necessity of discovering new biomarkers that could aid to predict disease outcome.In this study, we analyzed plasma circulating extracellular vesicles (EVs) from a cohort of 92 patients with different solid tumors (lung, breast, kidney cancer and melanoma) and found that newly diagnosed patients with brain metastases presented lower number of circulating particles and a higher protein concentration in small extracellular vesicles (sEVs) compared to patients without brain metastases and healthy controls. Out of all groups analyzed, melanoma patients with brain metastases presented decreased STAT3 activation and increased PD-L1 levels in circulating sEVs compared to patients without central nervous system metastases.The data presented in this work suggest that circulating sEVs may represent the immunosuppressive status of newly diagnosed brain metastases characterized by the reduced phospho-STAT3 (pSTAT3) and increased PD-L1, although the origin of these molecules found in circulating sEVs remains to be uncovered.

The management of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has changed in recent years due to the approval of new drugs. The aim of this study was to evaluate the prevalence, incidence, and treatment patterns in mHSPC in Spain.Multicenter, observational, longitudinal, retrospective study in routine clinical practice of patients diagnosed with mHSPC treated in Spanish hospitals between 2015 and 2019 (ECHOS study). Electronic medical records were extracted from BIG-PAC database, which contains geographically representative Spanish centers.Data from 379 men with mHSPC were included. The prevalence of mHSPC ranged between 12.2-14.6% per year, representing from 671 to 824 annual cases with an increasing trend. The mean incidence along the 4-year period was 2.5%, with annual incidence ranging 2.2-3.0%. New annual cases of de novo and recurrent disease ranged between 7-11 and 77-104, respectively, with no trend being observed. These patients were mostly recurrent (91%) with high-volume disease (68.6%). The most common first-line therapy was ADT combined with docetaxel (53%), followed by ADT alone (23.8%), combination of ADT and abiraterone (11.2%), and radiotherapy (8.6%). In the last 12 months before diagnosis of metastasis, most men had been submitted to radical prostatectomy (84.9%). The remaining patients had received radiotherapy (12%) or no treatment at all (3.8%).The ECHOS study provides epidemiologic data and current patterns of treatment in clinical practice of patients with mHSPC in Spain. These results emphasize the medical need of targeted treatments in these clinical settings.

Long considered an immunogenic tumour, immunotherapy has been the cornerstone of systemic treatment in renal cell carcinoma (RCC) for decades, since the introduction of interleukin 2 and interferon-alfa in the 1980s to the more recently approved immune checkpoint inhibitors. Moreover, on the basis that anti-CTLA-4 and anti-PD-1/PD-L1 intrinsic mechanisms are different, double checkpoint inhibition was proposed to further improve anti-tumor immune response. The first trial to assess double checkpoint inhibition was Checkmate 016 (nivolumab and ipilimumab). It showed acceptable safety and promising antitumor activity that led to the first phase III trial with combination immunotherapy in RCC, Checkmate 214. This trial showed superior overall survival and response rate of the combination immunotherapy (nivolumab and ipilimumab) versus sunitinib in intermediate- and poor-risk advanced RCC, leading to its approval in this setting. Despite these advances, there is still room for improvement. In this context, cytokines and T-cell costimulatory molecules are currently under investigation. This review summarizes the principles of immunotherapy and its role in RCC, provides an update on double checkpoint blockade and discusses the major challenges with double checkpoint blockade.

Some phase 2 trials had reported encouraging progression-free survival with Bevacizumab in monotherapy or combined with chemotherapy in glioblastoma. However, phase 3 trials showed a significant improvement in progression free survival without a benefit in overall survival. To date, there are no predictive biomarker of response for Bevacizumab in glioblastoma. We used Immunochemical analysis on tumor samples and pretreatment and post-treatment perfusion-MRI to try to identify possible predictive angiogenesis-related biomarkers of response and survival in patients with glioblastoma treated with bevacizumab in the first recurrence. We analyzed histological parameters: vascular proliferation, mitotic number and Ki-67 index; molecular factors: MGMT promoter methylation, EGFR amplification and EGFR variant III; immunohistochemical: MET, Midkine, HIF1, VEGFA, VEGF-R2, CD44, Olig2, microvascular area and microvascular density; and radiological: rCBV. In the statistical analysis, no significant correlation of any histological, molecular, microvascular or radiological parameters could be demonstrated with the response rate, PFS or OS with bevacizumab treatment. Unfortunately, in this histopathological, molecular, immunohistochemical and neuroradiological study we did not find any predictive biomarker of response or survival benefit for Bevacizumab in glioblastoma.

The role of neoadjuvant chemotherapy (NC) in resectable pancreatic cancer (RPC) has yet to be defined. This review aims to analyze the benefit of NC in RPC compared with upfront surgery (US) in terms of overall survival (OS) and disease-free survival (DFS).PubMed, CENTRAL (The Cochrane Library), and Embase were systematically reviewed until 3 November 2021. Abstract proceedings and virtual meeting presentations from the American Society of Clinical Oncology and the European Society of Medical Oncology conferences, reference articles of published clinical trials, and review articles were considered. Only randomized clinical trials (RCTs) comparing NC administration with or without radiotherapy previous with surgery (experimental arm) versus US followed by adjuvant chemotherapy with or without radiotherapy (control arm) for RPC were included.A total of 1135 studies were screened. Of these, 1117 studies were primarily excluded. Of the remaining 18 studies, 5 were excluded because of no adequate trial design for this work and 7 others had no available results. Finally, 6 trials with 469 patients with pancreatic cancer randomized to NC (n = 212) or US (n = 257) were selected. Compared with US, NC significantly improved OS [hazard ratio (HR) 0.75; 95% confidence interval (CI) 0.58-0.98; P = 0.033] and DFS (HR 0.73; 95% CI 0.59-0.89; P = 0.002). While the NC approach was not significantly associated with lower resection rate [relative risk (RR) 0.92; 95% CI 0.84-1.01; P = 0.069], the R0 resection rate was significantly higher for NC than for US (RR 1.31; 95% CI 1.13-1.52; P = 0.0004).This is the first meta-analysis of RCTs showing that NC improves OS for RPC compared with US followed by adjuvant therapy. Ongoing RCTs should confirm these findings with FOLFIRINOX to generalize the indication of NC.

Background A major breakthrough with immunotherapy is its potential to achieve complete responses (CR) in a subset of advanced renal cell carcinoma (RCC) patients. We aim at evaluating the incidence and relative risk (RR) of CR in RCC patients treated with immune checkpoint inhibitors (ICIs). Materials and methods Searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts prospective studies were identified. The proportion of patients with CR events and the derived 95% confidence intervals (CIs) were calculated for each study. Combined relative risks (RRs) and 95% CIs were calculated using fixed- or random-effects methods. The analysis was performed in the intention to treat population, in the PD-L1 expressing (≥1%) RCC tumors and in patients treated with the combination of ICIs and anti-VEGFR tyrosine kinase inhibitors. Results Six articles were considered for final analysis (total of 4.531 patients). The incidence of CR was 6.2% with ICIs and 2.6% with SOC. Treatment with ICIs significantly increased the risk of achieving CR compared to SOC (RR = 2.40; P = 0.001). This data was confirmed for patients treated with the combination of ICIs plus anti-VEGFR tyrosine kinase inhibitors (RR = 2.50; P = 0.002). In PD-L1 positive tumors, the incidence of CR was 10.0% with ICIs and 4.0% in the SOC arm (RR = 2.49; P Conclusions ICIs provide higher rates of CR compared to SOC, even higher in patients with PD-L1 positive tumors.

Càncer; Immunoteràpia; Ronyó Cáncer; Inmunoterapia; Riñón Cancer; Immunotherapy; Kidney In this article, we review de state of the art on the management of renal cell carcinoma (RCC) and provide recommendations on diagnosis and treatment. Recent advances in molecular biology have allowed the subclassification of renal tumours into different histologic variants and may help to identify future prognostic and predictive factors. For patients with localized disease, surgery is the treatment of choice with nephron-sparing surgery recommended when feasible. No adjuvant therapy has demonstrated a clear benefit in overall survival. Considering the whole population of patients with advanced disease, the combination of axitinib with either pembrolizumab or avelumab increase response rate and progression-free survival, compared to sunitinib, but a longer overall survival has only been demonstrated so far with the pembrolizumab combo. For patients with IMDC intermediate and poor prognosis, nephrectomy should not be considered mandatory. In this subpopulation, the combination of ipilimumab and nivolumab has also demonstrated a superior response rate and overall survival vs. sunitinib. In patients progressing to one or two antiangiogenic tyrosine-kinase inhibitors, both nivolumab and cabozantinib in monotherapy have shown benefit in overall survival compared to everolimus. Although no clear sequence can be recommended, medical oncologists and patients should be aware of the recent advances and new strategies that improve survival and quality of life in patients with metastatic RCC.

Urothelial bladder cancer (UC) is the most common malignancy involving the urinary system and represents a significant health problem. Immunotherapy has been used for decades for UC with intravesical bacillus Calmette-Guérin (BCG) set as the standard of care for non-muscle-invasive bladder cancer (NMIBC). The advent of immune checkpoint inhibitors (ICIs) has completely transformed the treatment landscape of bladder cancer enabling to expand the treatment strategies. Novel ICIs have successfully shown improved outcomes on metastatic disease to such an extent that the standard of care paradigm has changed leading to the development of different trials with the aim of determining whether ICIs may have a role in early disease. The localized muscle-invasive bladder cancer (MIBC) scenario remains challenging since the recurrence rate continues to be high despite all therapeutic efforts. This article will review the current experience of ICIs in the neoadjuvant setting of UC, the clinical trials landscape and finally, an insight of what to expect in the immediate and mid-term future.

Càncer de bufeta; Cistectomia; Quimioteràpia Cáncer de vejiga; Cistectomía; Quimioterapia Bladder cancer; Cystectomy; Chemotherapy The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific clinical–pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin–gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.

Introduction / Objectives MicroRNAs (miRNAs) constitute a new class of small noncoding RNAs that control post-transcriptionally the expression of gene products, either modulating directly protein translation, or regulating the stability of messenger RNA. There is increasing evidence of the role that miRNAs play in regulating breast cancer gene expression. However, there is little knowledge about the function and targets of miRNAs, and how they regulate complete processes or pathways. The main objective of this study was to unravel biological processes and signaling pathways regulated by miRNAs in breast cancer comparing their expression with the expression of the proteins they regulate. New statistical approaches were conducted in order to associate miRNA and protein quantification results with breast cancer subtype and to evaluate the association of miRNAs and protein expression patterns. Materials and Methods MicroRNA and protein expression were obtained from 79 breast cancer FFPE samples (16 TNBCs and 63 Luminal tumors). RNA was extracted from FFPE samples using RecoverAll (Ambion). MicroRNA expression was analyzed by RT-qPCR using TaqMan Arrays (Applied Biosystems). We selected for subsequent analysis those miRNAs with significant correlation between FF and FFPE samples. Protein extracts from FFPE samples were prepared in 2% SDS buffer using a protocol based on heat-induced antigen retrieval (Gámez-Pozo A et al. Mol Biosyst. 2011; 7: 2368-74). Protein abundance was calculated on the basis of normalized spectral protein intensity (LFQ intensity) using MaxQuant. Probabilistic graphical models are being applied successfully to represent complex biological systems as networks. In this phase of the study, we have chosen an appropriate methodology in the analysis of high dimensional data selecting a forest which minimizes the BIC criterion. This procedure extends the Chow and Liu's approach to the Gaussian case. The software used for implementation is based on the R library gRapHD. Results We measured the expression of 90 miRNAs in 79 breast cancer samples using RT-qPCR. We identified and quantified more than 3000 protein groups. We selected for subsequent analyses more than 1000 quantifiable proteins, defined as those identified at least in 75% of the samples in at least one type of sample with more than two unique peptides. Then, we analyzed the relations between miRNA and protein expressions. We identified miRNAs strongly related with processes considered as hallmarks of cancer, such as cellular adhesion, using probabilistic graphical models. Conclusions The integration of miRNA and protein expression patterns may be useful to describe how miRNAs regulate biological processes and signaling pathways in breast cancer. There is a need of new statistical approaches to evaluate these relations and to obtain meaningful information from such complex and massive data. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-07.

Background: microRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. In the present study, we describe miRNA expression in early node-positive BC and identify a 8-miRNA score that could contribute to prognosis assessment. Methods: First, microarray analysis was performed using RNA samples extracted from primary breast cancer. The expression of miRNAs was analyzed by RT-qPCR using the TaqMan Arrays from Applied Biosystems. After a suitable normalization of the 677 miRNAs analyzed, 123 presented a good correlation between their levels of expression in frozen tissue and paraffin tissue. A supervised analysis was done in order to identify MIR that could predict relapse. Results: 172 patients with node-positive chemotherapy-treated early BC were included in the present study. The median age at diagnosis was (53.7) years, 128 cases (74.4%) had positive estrogen receptor, and 163 patients (94,7%) received adjuvant chemotherapy. After a median follow up of 8,1 years, 71p (41.2%) relapsed. Supervised analyses identified 8 microRNAs (has miR-30e, miR-30a, miR-21, miR-210, miR-93, miR-150, miR-99b, miR-572) associated with higher risk of relapse (5 year PFS 50% vs 90%, HR 3.75, 95% CI 2.27–6.19) and with estimated overall survival (median not reached, HR 4.51, 95% CI 2.36–8.61). Interestingly, miRNAs defined 2 prognostic groups (high and low risk) regardless of type of adjuvant chemotherapy (with or without anthracyclines) and histological subtype (luminal A, B or triple negative). Conclusions: This study suggests that miRNA expression could contribute to assess molecular prognosis of breast cancer and identifies clusters of miRNAs that could improve outcome prediction. A validation study in node-negative and triple negative disease is planned. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-10-11.

Background MicroRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. In the present study, we describe miRNA expression in early node-positive BC and identify a 8-miRNA score that could contribute to prognosis assessment. Methods First, microarray analysis was performed using RNA samples extracted from primary breast cancer. The expression of miRNAs was analyzed by RT-qPCR using the TaqMan Arrays from Applied Biosystems. After a suitable normalization of the 677 miRNAs analyzed, 96 presented a good correlation between their expression in frozen and paraffin-embeded tissue. A supervised analysis was done in order to identify miR that could predict relapse. Results 172 patients with node-positive chemotherapy-treated early BC were included in the present study. The median age at diagnosis was (53.7) years, 128 cases (74.4%) had positive estrogen receptor, and 163 patients (94,7%) received adjuvant chemotherapy. After a median follow up of 8,1 years, 71p (41.2%) relapsed. Supervised analyses identified 8 microRNAs (has miR-30e, miR-30a, miR-21, miR-210, miR-93, miR-150, miR-99b, miR-572) associated with higher risk of relapse (5 year PFS 50% vs 90%, HR 3.75, 95% CI 2.27 – 6.19) and with estimated overall survival (median not reached, HR 4.51, 95% CI 2.36 – 8.61). Interestingly, miRNAs defined 2 prognostic groups (high and low risk) regardless of type of adjuvant chemotherapy (with or without anthracyclines) and histological subtype (luminal A, B or triple negative). Conclusions This study suggests that miRNA expression could contribute to assess molecular prognosis of breast cancer and identifies clusters of miRNAs that could improve outcome prediction. A validation study in node-negative and triple negative disease is planned. Disclosure All authors have declared no conflicts of interest.

Background RADIANT-3 was a phase III study investigating the effect of the mammalian target of rapamycin inhibitor everolimus on progression-free survival (PFS) in patients with advanced pancreatic neuroendocrine tumors (pNET; Yao et al, NEJM, 2011). Everolimus significantly improved PFS compared with placebo (11 vs 4.6 months, P Methods Baseline plasma levels of VEGF-A, PlGF, sVEGFR1, and sVEGFR2 were determined by ELISA using multiplexed MSD platform. The optimal cutoffs for these markers were explored using the “survival tree analysis” method. Interaction of treatment and baseline marker status ( Results PFS was significantly improved to a similar extent in patients receiving everolimus compared with patients who received placebo, regardless of baseline levels of markers (P Conclusions These exploratory analyses demonstrated consistent everolimus efficacy in all patients with advanced pNET irrespective of their baseline VEGF pathway biomarker levels. However, levels of VEGF-A, PlGP, and sVEGFR1 are potential prognostic factors for pNET. Marker Cutoff (pg/mL) Median PFS Prognostic effect HR [95% CI]; P value Treatment effect P value VEGF-A 246.1 8.3 vs 5.5 1.50 [1.17-1.92]; PlGF 32.06 8.0 vs 4.2 1.52 [1.14-2.02]; .004 SVEGFR1 226.2 8.3 vs 5.5 1.62 [1.27-2.07]; SVEGFR2 24503.1 10.8 vs 5.7 1.30 [0.96-1.76]; .090 Disclosure J.C. Yao: Consultant/advisory role for Novartis, Ipsen, Pfizer, Endo; Honoraria from Novartis; Research funding from Novartis, Genentech. M. Shah: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. A. Panneerselvam: Novartis employee. S. Stergiopoulos: Novartis employee. D. Chen: Novartis employee. M. Pavel: Honoraria for presentations and participation in Advisory Board Meetings: Novartis, Ipsen, Pfizer Research grant: Novartis. All other authors have declared no conflicts of interest.

Background Pazopanib is an oral tyrosine kinase inhibitor of the VEGFR, PDGFR and KIT with demonstrated clinical activity in NETs. The aims of our study were to assess efficacy, safety and potential predictive biomarkers of pazopanib in pts with NETs who may have received previous antiangiogenic or mTOR inhibitor treatment. Methods All pts had pancreatic or extra-pancreatic metastatic NET disease documented as progressive. Pazopanib 800 mg was given daily until disease progression (DP) or unacceptable toxicity. Primary endpoint was Clinical Benefit Rate (CBR) at 6 months (m) defined as Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) by RECIST-V-1.0. Optimal two-stage Simon design was utilized with H1 and H0 set at 70 % and 50 % respectively, Kaplan-Meier estimates were used for the analysis of time-to-event variables: 95% CI. Results 41 evaluable pts for response per protocol. 53.7% males, mean age 59.2 ± 10.3 years. At 6 months, 3 pts had PR (7.36%), 32 SD (78.0%), and 6 DP (14.6%), thus the CBR was 85.4%. Global median PFS 48,3 (13.9-82.7) weeks (w). By subgroups, CBR at 6 m and median PFS were 100% and 25.7 w in pts with no previous targeted therapy (9 pts), 88.9% and 48.3 w in pts with previous mTOR inhibitors (9 pts), 83.3% and 50.3 w in pts with previous antiangiogenics (16 pts) and 71.4% and 20.6 w in pts with previous antiangiogenics and mTOR inhibitors (7 pts) respectively. The sum of the longest diameter of target lesions had a decrease > 10% in 32.5 % of pts (37.5% without previous biological treatment, 22.2 % with previous mTOR inhibitor, 31.3% with prior multitarget inhibitor, and 42.9% with previous multitarget and mTOR, p = 0.506). Most frequent toxicities at of any grade were: asthenia (75%), diarrhoea (63%), nausea (42%). Translational studies on angiogenesis and inmunohistochemistry biomarkers and CTCs are ongoing. Conclusions Pazopanib 800 mg daily has promising activity in advanced NET regardless of previous treatment with other targeted therapies. This trial suggests the role that treatment sequencing with novel targeted agents may have in NETs. Disclosure All authors have declared no conflicts of interest.

376 Background: Recently, new targeted therapies have proved the efficacy in patients with mRCC in terms of progression-free survival (PFS) and overall survival (OS). There is also growing evidence that successive targeted treatments has achieved objective responses and sustained time to progression. Here, we report data from our insitution analysing the OS benefit of continuing targeted therapy after disease progression. Methods: We identified 58 metastatic clear cell RCC patients who started targeted therapy between September 2005 and December 2008. The data were collected from our clinical trials registry. The patients were evaluated for differences in baseline characteristics and known prognostic factors (PFs) in metastatic RCC. We assessed overall survival for all patients. Results: We identified 58 pts, 24 are still alive (43%). Median age was 56 (range 31–78). ECOG PS 0/1/2: 33/24/1. 46% (27) had diagnosis to treatment intervals < 1 year. Sites of metastatic disease included: lung 46%(26), bone 32%(19), hepatic 29%(17) and retroperitoneal 24%(14). Nephrectomy was pesented in 90% of all pts. The number of metastases location was: 1/2/3: 32%/11%/7%. The drugs administered are listed in table. Median number of treatments: 3 (range 1–7). The median overall survival (OS) was 44 months and the 3- year OS was 60.4%. Pts by MSKCC risk-group were: favourable prognostic (FP) 19%, intermediate prognostic (IP) 63%, poor prognostic (PP) 18%. The overall survival for FP group was not reached, and 3-year OS was 81%; for IP group the median survival time was 44 months and 3-year OS was 59%; and for PP group the median survival time was 25 months. Conclusions: The survival for patients with mRCC who receive multiple lines of targeted therapy has increased to close to 4 years. These results indicate a clear shift in the evolution of mRCC but lack a great deal about what the best sequence. Final analysis of the best sequence of treatment will be presented at the meeting. [Table: see text]

e11031 Background: The addition of trastuzumab as adjuvant treatment has allowed 50% reduction for relapse in >1cm size tumor, early-stage HER2-positive breast cancer (BC). However, it is not clear if this benefit is present as well in smaller, node-negative (N0) tumors. We retrospectively reviewed our experience in a single institution. Methods: From 1997 to 2007, BC patients (pts) with HER2-positive, T1a-b N0, early BC were included. Epidemiologic, clinical and characteristic tumor data were collected from patients at 12 de Octubre University Hospital (Madrid) Results: 35 pts with a median age of 55 years (range 35-82) were included. Six pts (17%) had T1a (≤ 0,5 cm) tumors and 29 (83%) T1b (0,5-1 cm). All cases had no lymph node involvement, tested by lymphadenectomy (30 pts, 86%) or sentinel-node biopsy (5 pts, 14%). Eighteen pts (51%) underwent mastectomy and 17 pts (49%) conservative surgery. Most frequent histology was infiltrating ductal carcinoma (31pts, 89 %). HER2 testing was performed by IHC in...

e11008 Background: Lapatinib (L) plus capecitabine is an FDA-approved regimen for patients with HER2+ MBC who have previously received trastuzumab. The aim of this study was to evaluate the efficac...

e19639 Background: Palliative chemotherapy (CT) is the mainstay in the management of advanced pancreatic adenocarcinoma (PaC). To assess the efficacy of different gemcitabine regimens in the day to...

In 51 children with tuberculosis of the hip, overall end results were better, and the range of motion was improved when irrigation-suction with Streptomycin was included in the regimen of surgical management.