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Background Sunitinib, pazopanib, sorafenib, axitinib and bevacizumab are the five recommended antiangiogenic agents in first-line therapy for metastatic renal cell carcinoma (mRCC). Because these drugs underwent simultaneous clinical development, no direct efficacy and safety comparison was ever conducted, thus preventing optimal therapy choices. Methods We performed a traditional and network meta-analysis to evaluate the efficacy and safety of mRCC-recommended first-line antiangiogenic agents. After a systematic review of Medline and Embase up to July 2014, we identified randomized clinical trials (RCTs) evaluating the outcomes of mRCC patients treated with sunitinib, pazopanib, sorafenib, axitinib and bevacizumab as first-line treatment. Endpoints of interest were response rate, progression-free survival (PFS), overall survival (OS), and safety. Results We screened 769 abstracts and included nine RCTs with a total of 4282 patients. In the weighted pooled analysis, first-line antiangiogenic agents showed significant improvement in PFS (HR = 0.6; 95% IC, 0.51–0.72) and OS (HR = 0.85; 95% IC, 0.78–0.93) compared to control (placebo or interferon-alpha2a (INF)). Network meta-analysis showed no significant differences among antiangiogenic drugs in 6-month PFS, 1-year OS, disease control rate and drug-related safety for all-grade hypertension, diarrhea, weight-loss, nausea or anorexia. However, pazopanib showed a lower incidence of fatigue, anemia and hand foot skin reaction. Conclusions This meta-analysis confirms the benefits of first-line antiangiogenic therapy in mRCC, with an improvement in OS. Sunitinib, pazopanib, axitinib and bevacizumab + INF offer similar efficacy but different safety profiles which can help clinicians to better personalize treatment decisions in patients with mRCC.

Chemotherapy, as all systemic treatments, is generally effective in brain metastases because the brain blood barrier (BBB) does not affect treatment's diffusion. Platinum-based chemotherapy provides response rates ranging from 23 to 50% for brain metastases. Anti-EGFR therapies are effective mostly when a somatic EGFR activating mutation is detected, or in selected population (adenocarcinoma, Asian population, never-smokers and women): response rate ranges from 38 to 69.6%. Bevacizumab is now allowed for non-small cell lung cancer (NSCLC) patients with brain metastases and non-squamous histology. The presence of untreated brain metastases may not influence its efficacy combined with paclitaxel-carboplatin. The best sequence for multimodality management of brain metastases has to be established but upfront systemic treatments in patients with asymptomatic brain metastases is a valid option.

Objectifs La reponse au traitement par acetate d’abiraterone (AA) est heterogene chez les patients atteints d’un cancer de la prostate en phase de resistance a la castration (CPRC). Le but de cette etude retrospective etait d’evaluer les caracteristiques cliniques et biologiques de la maladie initiale et au moment de l’introduction d’AA afin de determiner d’eventuelles facteurs predictifs de reponse. Methodes Nous avons realise une recherche retrospective des patients traites par AA dans notre centre entre fevrier 2005 et janvier 2013. Ont ete exclus les patients sans donnees biologiques, ayant participe a des etudes cliniques ou decedes d’une cause non liee au CPRC. La reponse au traitement par AA a ete evaluee en 3 sous-groupes selon le temps de reponse au traitement : longs repondeurs (LR, > 9 mois), refractaires (RF, ≤ 4 mois) et intermediaires (4–9 mois). Les caracteristiques cliniques et biologiques de la maladie initiale et au moment de debuter l’AA ont ete recueillis et analyses dans chaque un des sous-groupes ( Tableau 1 , Tableau 2 ). Resultats Au total, 31 patients ont ete inclus avec un suivi moyen de 18,8 mois (1,8–64,7) avec un âge moyen de 72,4 ans (45,5–93,7). Soixante-et-un avait eu un traitement par chimiotherapie et 39 % etaient chimionaifs. Pour les patients RF (16 %) et les LR (48 %) la survie globale etait respectivement de 23 versus 98 mois et la survie apres la fin d’AA de 1 versus 9 mois. Tous les patients RF etaient symptomatiques, metastatiques d’emblee, et avaient un Gleason ≥ 8. Les groupes RF et LR presentaient respectivement une velocite de PSA moyen de 182,5 versus 7,61 ng/ml/mois avant le debut du traitement. Aucune autre variable clinique ou biologique n’a permis de montrer une difference parmi les 3 groupes etudies. Conclusion Sous reserve du nombre limite de patients, la cinetique du PSA avant le debut du traitement par AA semble etre le facteur predictif le plus precis pour predire la reponse a ce traitement chez les patients atteints du CPRC. Une evaluation prospective de cette variable est en cours dans notre centre.

Chemotherapy, as all systemic treatments, is generally effective in brain metastases because the brain blood barrier (BBB) does not affect treatment's diffusion. Platinum-based chemotherapy provides response rates ranging from 23 to 50% for brain metastases. Anti-EGFR therapies are effective mostly when a somatic EGFR activating mutation is detected, or in selected population (adenocarcinoma, Asian population, never-smokers and women): response rate ranges from 38 to 69.6%. Bevacizumab is now allowed for non-small cell lung cancer (NSCLC) patients with brain metastases and non-squamous histology. The presence of untreated brain metastases may not influence its efficacy combined with paclitaxel-carboplatin. The best sequence for multimodality management of brain metastases has to be established but upfront systemic treatments in patients with asymptomatic brain metastases is a valid option.

e15528Background: The average age of patients (pts) diagnosed with gastric cancer (GC) is 69 yrs. In resectable GC, multimodal approach is the standard of care but its choice and feasibility in unk...

e15586 Background: Four different antiangiogenic treatment are approved in first line advanced Renal Cell Carcinoma (RCC): sunitinib (Su), pazopanib (Pa), sorafenib (So) and bevacizumab (Be). Due t...

e17664 Background: Because of weak solubility in water, many cytotoxics are dissolved in ethanol. FDA recently raised alert noticing that patients could be intoxicated after their treatments. The m...

37 Background: Adjuvant chemotherapy’s role after radical prostatectomy (RP) remains controversial in localized high-risk prostate cancer (HRPC). This phase II trial assessed the combination of weekly paclitaxel (WP) with androgen deprivation therapy (ADT) in this population. Methods: All eligible patients (pts) had undergone a laparoscopic RP with pelvic lymph node dissection for a localized HRPC defined with ≥1 of the following criteria: T3b-T4 post-operated Gleason score (GS) ≥8, PSA≥ 20 ng/mL, pN+, in Henri Mondor Hospital. Pts were randomly assigned to either triptoreline 11.25mg every 3 months during 3 years and 8 cycles of WP 100 mg/ m2 (WP arm, n=21) or triptoreline alone (ADT arm, n=26). The primary endpoint is disease free survival (DFS); events=PSA relapse, clinical and radiographic relapse, death. The planned number of pts was 152. Toxicity results indicated a good tolerability with neutropenic fever in 4.3% (n=1), and no negative impact on QoL in the WP arm (Ploussard, Prostate Cancer Prostatic Dis. 2010). Here we report 8-year DFS and overall survival (OS) results. Results: Between February 2005 and October 2007, 47 pts were enrolled. This trial was terminated prematurely because of slow accrual. After a mean follow-up of 8.4 y, we identified a PSA relapse in 25 pts (53%) and castrate-resistant prostate cancer occurred in 6 pts. No statistically difference was found in terms of either biochemical or clinical DFS (bDFS, cDFS) and OS: 8-year bDFS rate: 50% [n=11/22] in the WP arm vs 46% [n=12/26] in the ADT arm (p=0.79); 8-year cDFS rate: 95.4% [n=21/22] in the WP arm vs 88.5% [n=23/26] in the ADT arm (p=0.38). The 8-year OS rate is 90.9% (n=20/22) and 84.6% (n=22/26) respectively with no difference between treatment arms (p=0.51). No clinical, histological or biological variable demonstrated a difference in either 8-year bDFS, cDFS or OS rate. Conclusions: Provided that this trial is probably underpowered to detect a DFS benefit, adjuvant weekly paclitaxel after RP was not associated with any significant reduction in the risk of biological relapse or death compared to ADT alone in patients with localized HRPC. Chemotherapy should be only proposed in dedicated clinical trial for localized HRPC.