The Oncologist 2012;17:15-25 www.TheOncologist.com Patients and Methods. Patients were randomly assigned to receive six cycles of bevacizumab, capecitabine, and oxaliplatin every 3 weeks followed by XELOX plus bevacizumab or bevacizumab alone until progression. The primary endpoint was the progression-free survival (PFS) interval; secondary endpoints were the overall survival (OS) time, objective response rate (RR), time to response, duration of response, and safety.Results. The intent-to-treat population comprised 480 patients (XELOX plus bevacizumab, n ؍ 239; bevacizumab, n ؍ 241); there were no significant differences in baseline characteristics. The median follow-up was 29.0 months (range, 0 -53.2 months). There were no statistically significant differences in the median PFS or OS times or in the RR between the two arms. The most common grade 3 or 4 toxicities in the XELOX plus bevacizumab versus bevacizumab arms were diarrhea, hand-foot syndrome, and neuropathy. Conclusion. Although the noninferiority of bevacizumab versus XELOX plus bevacizumab cannot be confirmed, we can reliably exclude a median PFS detriment >3 weeks. This study suggests that maintenance therapy with singleagent bevacizumab may be an appropriate option following induction XELOX plus bevacizumab in mCRC patients. The Oncologist 2012;17:15-25
The data from this exploratory study suggest that the accumulation of molecular events seems to influence the outcome of HL, particularly in the low-IPS group.
PURPOSESomatostatin analogs (SSAs) are recommended for the first-line treatment of most patients with well-differentiated, gastroenteropancreatic (GEP) neuroendocrine tumors; however, benefit from treatment is heterogeneous. The aim of the current study was to develop and validate a progression-free survival (PFS) prediction model in SSA-treated patients.PATIENTS AND METHODSWe extracted data from the Spanish Group of Neuroendocrine and Endocrine Tumors Registry (R-GETNE). Patient eligibility criteria included GEP primary, Ki-67 of 20% or less, and first-line SSA monotherapy for advanced disease. An accelerated failure time model was developed to predict PFS, which was represented as a nomogram and an online calculator. The nomogram was externally validated in an independent series of consecutive eligible patients (The Christie NHS Foundation Trust, Manchester, United Kingdom).RESULTSWe recruited 535 patients (R-GETNE, n = 438; Manchester, n = 97). Median PFS and overall survival in the derivation cohort were 28.7 (95% CI, 23.8 to 31.1) and 85.9 months (95% CI, 71.5 to 96.7 months), respectively. Nine covariates significantly associated with PFS were primary tumor location, Ki-67 percentage, neutrophil-to-lymphocyte ratio, alkaline phosphatase, extent of liver involvement, presence of bone and peritoneal metastases, documented progression status, and the presence of symptoms when initiating SSA. The GETNE-TRASGU (Treated With Analog of Somatostatin in Gastroenteropancreatic and Unknown Primary NETs) model demonstrated suitable calibration, as well as fair discrimination ability with a C-index value of 0.714 (95% CI, 0.680 to 0.747) and 0.732 (95% CI, 0.658 to 0.806) in the derivation and validation series, respectively.CONCLUSIONThe GETNE-TRASGU evidence-based prognostic tool stratifies patients with GEP neuroendocrine tumors receiving SSA treatment according to their estimated PFS. This nomogram may be useful when stratifying patients with neuroendocrine tumors in future trials. Furthermore, it could be a valuable tool for making treatment decisions in daily clinical practice.
We analyzed 104 patients with non-Hodgkin's lymphoma, follicular or diffuse large-B-cell-type lymphoma, in order to evaluate the correlation between clinical characteristics and immunohistochemical parameters. Immunostaining was performed by means of monoclonal antibodies against Ki-67, bcl-2, and p53 expression. Forty-nine of the patients showed follicular lymphoma. A high expression of bcl-2 was found in 93%, high expression of p53 in 57%, and low expression of Ki-67 in 96%. Follicular lymphoma grade III showed a p53 expression (p = 0.07) slightly higher than follicular lymphoma grades I and II, not reaching statistical significance. Follicular lymphoma grades I and II tended to express lower Ki-67 and higher levels of bcl-2 expression than grade III (p = 0.06). Fifty-five cases showed diffuse large-B-cell lymphoma. Among them, bcl-2 was absent in 39%, whereas p53 and Ki-67 expression were high in 38%. In the diffuse large-B-cell lymphomas, a high bcl-2 expression correlated with stages III and IV (p = 0.03) and involvement of more than one extranodal area (p = 0.03). High Ki-67 expression was also associated to extranodal involvement of more than one area (p = 0.03). Overall survival of patients did not show statistically significant differences regarding Ki-67, bcl-2, and p53 tumoral expression. Prognostic factors for overall survival in the multivariate analysis were age (p = 0.02) and LDH (p = 0.003). Time to progression was worse among follicular lymphoma with high p53 expression than with mild/moderate p53 expression (p = 0.009).
Gastroenteropancreatic neuroendocrine neoplasms are tumors of widely variable clinical behavior, roughly stratified by the World Health Organization (WHO) 2010 classification into three subgroups based on proliferation index. Real-world data from 2,813 patients of the Spanish Registry RGETNE demonstrated substantial clinical heterogeneity within grade (G) 2 and G3 neuroendocrine neoplasms. Tumor morphology and further subdivision of grading substantially improves prognostic stratification of these patients and may help individualize therapy. This combined, additive effect shall be considered in future classifications of neuroendocrine tumors and incorporated for stratification purposes in clinical trials.
Background: Surufatinib, a kinase inhibitor targeting vascular endothelial growth factor receptors, fibroblast growth factor receptor 1 and colony stimulating factor-1 receptor, has demonstrated superior efficacy in extra-pancreatic neuroendocrine tumors (NETs) in a prior phase III study (ESMO 2019 Abs. LBA76). Here we report results from a parallel study of surufatinib in pancreatic NETs (pNETs). Methods: The study evaluated the efficacy and safety of S in Pts with well-differentiated (pathological grade 1 or 2), progressive, unresectable or metastatic pNETs. Pts were randomized in a 2:1 ratio to receive S or P, 300 mg, orally, once daily, until disease progression or intolerable adverse events. Crossover at disease progression was allowed. The primary endpoint was investigator-assessed progression-free survival (PFS). Results: By the cutoff date on 11 November 2019 for the pre-planned interim analysis, 172 Pts were randomized, 113 pts to S and 59 to P. Baseline characteristics were well balanced. The study met the primary endpoint; investigator-assessed median PFS was 10.9 vs. 3.7 months in S and P arms, respectively, with hazard ratio (HR)¼0.491; 95% confidence interval [CI]: 0.319e0.755; p¼0.0011. Analysis by a blinded independent radiology committee confirmed PFS improvement (13.9 vs. 4.6 months; HR¼0.339; 95% CI: 0.209e0.549; p<0.0001). The investigator-assessed objective response rate was 19.2% with S and 1.9% with P (p¼0.0021). Most common (5% in either arm) grade 3 treatment-emergent adverse events (TEAEs) were hypertension (38.9% in S arm vs. 8.5% in P arm), proteinuria (9.7% vs. 1.7%), hypertriglyceridaemia (7.1% vs. 0), alanine aminotransferase increased and gamma-glutamyltransferase increased (both 2.7% vs. 5.1%). TEAEs leading to drug discontinuation occurred in 10.6% pts vs. 6.8% pts in S and P arm respectively. Conclusions: Surufatinib significantly improved the PFS in Pts with progressive, welldifferentiated advanced pNETs. The safety profile was manageable and consistent with observations in prior studies. Surufatinib represents a promising treatment option in the armamentarium against pNETs. Clinical trial identification: NCT02589821.
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