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Purpose The phase III VELOUR trial demonstrated efficacy with combined FOLFIRI‐aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without bevacizumab versus placebo. The effect of FOLFIRI‐aflibercept in routine clinical practice was evaluated. Methods/Patients Overall survival (OS), progression‐free survival (PFS), response and safety were analysed for 78 patients treated with FOLFIRI‐aflibercept at six GITuD institutions. Exploratory analyses of prognostic and predictive markers of efficacy were performed. Results Patients had good general status (PS 0‐1 96.2%), tumours were mostly RAS‐mutant (75.6%), synchronous (71.8%), and left‐sided (71.8%). Prior therapy included bevacizumab (47.4%) and anti‐EGFR agents (12.8%). PFS was longer for metachronous than synchronous tumours (11.0 vs 5.0 months, P = 0.028), and for left‐colon tumours (7.0 vs 3.0 months, P = 0.044). RAS‐mutant status, first‐line treatment and primary tumour surgery did not impact PFS. The disease control rate was 70.5%. The most common grade 3/4 toxicities were neutropenia (15.3%), asthenia (10.3%), diarrhea and mucositis (6.4% each). Dysphonia was reported in 39.7% of patients, and grade 3 hypertension in 3.8%. Development of hypertension (any grade) was significantly associated with a reduced risk of progression by multivariate analysis (HR = 2.7; 95%CI 1.3‐5.4; P = 0.001). Conclusions Efficacy with FOLFIRI‐aflibercept in a real‐life population was in line with results from the pivotal trial and toxicity was manageable with treatment adaptation. Survival outcomes were not impacted by primary tumour location, RAS‐mutant status, first‐line treatment or primary tumour surgery. Hypertension may be a surrogate marker of efficacy in this patient population.

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The Hedgehog (Hh) family of intercellular signalling proteins have come to be recognised as key mediators in many fundamental processes in embryonic development. Their activities are central to the growth, patterning and morphogenesis of many different regions within the bodies of vertebrates. In some contexts, Hh signals act as morphogens in the dose-dependent induction of distinct cell fates within a target field, in others as mitogens in the regulation of cell proliferation or as inducing factors controlling the form of a developing organ. These diverse functions of Hh proteins raise many intriguing questions about their mode of action. Various studies have now demonstrated the function of Hh signalling in the control of cell proliferation, especially for stem cells and stem-like progenitors. Abnormal activation of the Hh pathway has been demonstrated in a variety of human tumours. Hh pathway activity in these tumours is required for cancer cell proliferation and tumour growth. Recent studies have uncovered the role for Hh signalling in advanced prostate cancer and demonstrated that autocrine signalling by tumour cells is required for proliferation, viability and invasive behaviour. Thus, Hh signalling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring.

A 75-year-old-man, with a 2-month history of abdominal pain, underwent a standard diagnostic workup that included a CT scan that showed a large right renal mass and subcentimeter nodes in the right and left lung lobes. In December 2003, the patient underwent right nephrectomy with adrenalectomy and a diagnosis of renal cell carcinoma (pT3N0M0 stage) was made. No further treatment was proposed and patient was followed up regularly. In October 2006, the annual gastrointestinal endoscopy showed asymptomatic multilobulated and polypoid masses in the gastric fundus and gastric body that corresponded to metastasis of the renal carcinoma that had been resected three years ago. Surgical treatment was refused and oral treatment with sunitinib (50 mg/day consecutively for 4 weeks followed by 2 weeks off) was initiated. Patient completed one cycle and development of acute toxicity (grade 3 asthenia, anorexia and mucositis) led to treatment interruption. After recovering from acute toxicity, the patient was proposed to reinitiate treatment with dose reduction, but he refused any medical treatment. At the follow-up visit, three months later, the gastrointestinal endoscopy showed four unspecific 2 mm nodules without malignant evidence. The whole-body CT did not reveal any other abnormality except for the known lung nodes. PET scan six months after treatment confirmed complete gastric response.