Annalisa Guida

Prognostic role of gender in diffuse large B-cell lymphoma treated with rituximab containing regimens: a Fondazione Italiana Linfomi/Grupo de Estudos em Moléstias Onco-Hematológicas retrospective study.

Male gender was recently reported as an adverse prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). We conducted a retrospective study of adult patients with DLBCL initially treated with rituximab containing regimens between 2001 and 2007. Patients were identified from the clinical archives of 43 Italian and Brazilian institutions. The principal endpoint was overall survival (OS). One thousand seven hundred and ninety-three patients were fully eligible for the study. Thirty-eight percent, 27%, 22% and 12% of patients had an International Prognostic Index (IPI) score of 0–1, 2, 3 and 4–5, respectively; 53% were males. After a median follow-up of 36 months (1–106), the 5-year OS was 76% (95% confidence interval 74–78%). In univariate analysis, male gender was an adverse prognostic factor with a hazard ratio of 1.52. In multivariate analysis, when adjusted by IPI, again gender maintained its prognostic relevance, showing an independent additive effect. In conclusion, in patients with DLBCL treated with rituximab containing regimens, gender may increase the predictive power of the IPI. Based on these results, given possible differences in blood clearance of rituximab between males and females, the benefit of higher doses of rituximab in males should be explored.

Clinical outcome of patients who reduced sunitinib or pazopanib during first-line treatment for advanced kidney cancer

OBJECTIVES To investigate the different outcomes in patients with metastatic renal cell carcinoma (mRCC) who receive a reduced first-line dose of sunitinib or pazopanib compared to those who continue at the standard dose. PATIENTS AND METHODS All the patients treated in 11 oncological centers in Italy for mRCC who started first-line treatment with sunitinib or pazopanib at the standard dose. Descriptive statistical tests were used to highlight differences among groups. Survival was estimated by the Kaplan-Meier method and compared across the groups using log-rank tests, the Cox proportional hazards model adjusted for statistically significant variables was also done. RESULTS A total of 591 patients were included in the study. Of these, 45.7% received a reduced dose of sunitinib or pazopanib after a median treatment time of 3.6 months at the standard dose. The median overall survival in the patients who continued to receive the standard dose was 24.0 months compared to 49.4 months for those who received a reduced dose (hazard ratio = 1.80; 95% CI: 1.42-2.29; P<0.001). Only 45% of the patients received second-line therapy: 42.5% had an mTOR and 54.1% a tyrosine kinase inhibitor. Second-line overall survival was 19.8 and 11.8 months, respectively, in the patients who received, or did not, a reduced dose during first-line therapy (P = 0.007). CONCLUSIONS Toxicity-related dose reduction is a common event in mRCC patients who have started first-line therapy with either sunitinib or pazopanib. This is positively related to the outcomes of both first- and second-line therapy.

Retrospective analysis on safety and efficacy of everolimus in treatment of metastatic renal cancer patients receiving dialysis

AIMS This retrospective study aimed to investigate safety and efficacy of everolimus in patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease requiring dialysis. PATIENTS & METHODS From November 2009 to December 2012, 11 mRCC patients undergoing dialysis were treated with everolimus after failure of anti-VEGF therapy at six Italian institutions. Patient characteristics, safety and outcomes were collected. RESULTS Progression-free survival and overall survival were determined using the Kaplan-Meier method. Median progression-free survival and overall survival were 9.01 and 15.7 months, respectively. No unexpected adverse events were reported. CONCLUSION Everolimus appears to be safe in mRCC patients with renal impairment or end-stage renal disease requiring dialysis. Larger prospective studies are required to confirm these findings.

Use of 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography in patients with Hodgkin lymphoma in daily practice: a population-based study from Northern Italy.

We conducted a population-based study to assess how positron emission tomography (PET) is currently used in patients with Hodgkin lymphoma (HL). Four cancer registries from northern Italy were used to identify patients with HL diagnosed from 2006 to 2008. Computed tomography (CT) and PET scans were collected before treatment start (B), at the end (F), and during treatment (I). One hundred and thirty-six patients were identified as the study population. B-PET, I-PET, and F-PET were performed in 82%, 65%, and 85% of patients, respectively. Overall, I-PET was coded as positive in 16% of cases. F-PET was positive in 13% of cases. The I-PET result was a prognostic factor for failure-free survival (FFS) (hazard ratio [HR] 5.33); the F-PET result was the only prognostic factor for overall survival (OS) (HR 14.2). This population-based study confirms the prognostic role of I-PET for FFS also in daily practice; the results of F-PET can be used to predict OS.

Treating patients with renal cell carcinoma and bone metastases

ABSTRACT Introduction: Bone metastases (BMs) are common and cause morbidity in cancer patients. This review focuses on evidence in BMs from metastatic renal cell carcinoma (mRCC) management and discusses current evidence on the role of systemic treatments in BMs management, bone-targeting agents’ benefits in skeletal-related events prevention and local therapeutic approaches to BM in mRCC. Areas covered: A comprehensive review of literature concerning incidence, prognosis, and therapeutic approaches of BMs was performed, focusing on the latest emerging evidence in management of BMs from mRCC. Expert commentary: One-third of mRCC patients present metastatic disease to the bone. BMs impact negatively the prognosis and decrease quality of life. Adequate management of BMs from RCC requires a multimodal evaluation to optimize care and quality of life. Both tyrosine-kinase inhibitors and immunotherapy may be effective in BMs treatment. BMs cause severe complications such as fracture, spinal cord compression, and pain requiring surgery or radiotherapy and several local approaches are available to achieve a local control of the disease. Defining prognosis of systemic disease and identifying the main goal of treatment is crucial for the selection of the best strategy.

“To Cut or Not to Cut”, a Biomolecular Approach to Metastasectomy in Metastatic Clear Cell Renal Cell Carcinoma

In recent years, guidelines for the optimal management of metastatic clear cell renal cell carcinoma (mccRCC) have been changed continuously [1]. In 2005, we moved from the old immunotherapy approaches to the antiangiogenic era, with a major increase in terms of disease control rate and progression-free survival (PFS). More recently, immunotherapy came back into clinical practice with the new checkpoint inhibitors, which provide marked advantages in overall survival (OS) [2,3]. Moreover, the ongoing revolution in the treatment paradigm for patients with mccRCC comprises some other important aspects. Indeed, our understanding of renal carcinoma has evolved over the past few years. ccRCC is no longer considered a single disease entity, but rather a heterogeneous disease, consisting of many different subtypes, each one with distinctive genetic and molecular alterations, a different clinical course, and potentially, different responses to therapy. For instance, poor-risk patients or cases with sarcomatoid features usually present poor outcome and derive limited benefits from antiangiogenic agents, but may have important benefits from checkpoint inhibitors. On the other hand, antiangiogenic agents have been also recently confirmed as the best option for good-risk patients [2,4]. New evidence from recent trials comparing different and innovative drug combinations (ipilimumab plus nivolumab or bevacizumab plus atezolizumab) with sunitinib, and also evaluating the prognostic and possibly predictive role of the PD-L1 status and prognostic risk classification (mainly good-risk versus intermediate/poor-risk cases) will likely

Safety and efficacy of pazopanib in first-line metastatic renal cell carcinoma with or without renal failure: the CORE-URO-01 study

Background Pazopanib has been approved for first‐line treatment of patients with metastatic renal‐cell carcinoma on the basis of clinical trials that enrolled only patients with adequate renal function. Few data are available on the safety and efficacy of pazopanib in patients with renal insufficiency. This study investigated the effect of kidney function on treatment outcomes in such patients. Patients and Methods We retrospectively analyzed data of metastatic renal‐cell carcinoma patients treated with pazopanib from January 2010 to June 2016 with respect to renal function. Patients with Modification of Diet in Renal Disease ≤ 60 mL/min/1.73 m2 (group A) were compared to patients with Modification of Diet in Renal Disease > 60 mL/min/1.73 m2 (group B) in terms of progression‐free survival, toxicities, response rates, and overall survival. Results A total of 229 patients were included: 128 in group A and 101 in group B. Median progression‐free survival was 14 months (95% confidence interval [CI], 9.4‐18.5) and 17 months (95% CI, 11.4‐22.8), and overall survival was 30.5 months (95% CI, 8‐53) and 41.4 months (95% CI, 21‐62) for group A and group B, respectively, with no significant difference (P = .6). No significant difference between the 2 groups was reported in the incidence of adverse events. Dose reductions were more frequent in group A patients (66% vs. 36%; P = .04). Conclusion Although the dose of pazopanib was reduced more frequently in patients with renal impairment, kidney function at therapy initiation does not adversely affect the safety and efficacy of pazopanib. Micro‐Abstract Few data are available on pazopanib in patients with renal insufficiency. We investigated the effect of kidney function on treatment outcomes. Kidney function at time of pazopanib initiation does not affect the drug’s safety and efficacy.

Everolimus Versus Axitinib as Second-line Therapy in Metastatic Renal Cell Carcinoma: Experience From Institut Gustave Roussy

Microabstract: We analyzed 126 patients with metastatic renal cancer treated with everolimus (n = 81) and axitinib (n = 45) after failure of first‐line vascular endothelial growth factor‐targeted therapy. Even if new therapies did in fact emerge, they are not widely available, and our results increase the knowledge of renal cancer. Background: Everolimus (E) and axitinib (A) have been standard treatments for patients with metastatic renal cell carcinoma after failure of first‐line therapy (1L) with vascular endothelial growth factor‐targeted therapy. This study aims to compare both drugs in a large comprehensive cancer center. Methods: Patient characteristics and outcome data from all patients with metastatic renal cell carcinoma who received E or A as second‐line therapy at Gustave Roussy from April 2007 to May 2015 have been recorded. Results: A total of 81 patients were treated with E and 45 patients with A. There were no major differences between the 2 groups. The most common 1L was sunitinib (79% in the E group and 82.2% in the A group). The median follow‐up was 29 months; 26 months for A and 33 months for E (P = .046). The median overall survival (OS) was 21.5 months for E and 14.9 months for A (P = .23). The median progression‐free survival (PFS) was 5.3 and 7.7 months for E and A, respectively (P = .39). Partial response was achieved in 4% and in 24% of patients (P = .002) in the E and A cohort, respectively. In the A group, the median PFS and OS were statistically different according to response, tumor burden, and 1L duration. No differences were found in the E arm. Conclusion: In this series, there are no significant differences for PFS and OS with E and A. A appears to provide more objective response. A appears to be more effective in patients with small tumor burden, responders to 1L, and 1L therapy > 12 months.

Real-life clinical practice results with vinflunine in patients with relapsed platinum-treated metastatic urothelial carcinoma: an Italian multicenter study (MOVIE-GOIRC 01–2014)

BackgroundVinflunine is the only chemotherapeutic agent shown to improve survival in platinum-refractory patients with metastatic transitional cell carcinoma of the urothelium (TCCU) in a phase III clinical trial, which led to product registration for this indication in Europe. The aim of this study was to assess the efficacy of vinflunine and to evaluate the prognostic significance of risk factors in a large, unselected cohort of patients with metastatic TCCU treated according to routine clinical practice.MethodsThis was a retrospective multicenter study. Italian cancer centers were selected if, according to the Registry of the Italian Medicines Agency (AIFA), at least four patients had been treated with vinflunine between February 2011 and June 2014, after first- or second-line platinum-based chemotherapy. The primary objective was to test whether the efficacy measured by overall survival (OS) in the registration study could be confirmed in routine clinical practice. Multivariate analysis was carried out using Cox proportional hazard model.ResultsA total of 217 patients were treated in 28 Italian centers. Median age was 69 years (IQR 62–76) and 84% were male; Eastern Cooperative Oncology Group performance status (ECOG PS) was ≥ 1 in 53% of patients. The median number of cycles was 4 (IQR 2–6); 29%, 35%, and 36% received an initial dose of 320 mg/m2, 280 mg/m2 or a lower dose, respectively. Median progression-free survival (PFS) and OS for the entire population was 3.2 months (2.6–3.7) and 8.1 months (6.3–8.9). A complete response was observed in six patients, partial response in 21, stable disease in 60, progressive disease in 108, with a disease control rate of 40%. Multivariate analysis showed that ECOG PS, number of metastatic sites and liver involvement were unfavorable prognostic factors for OS. Toxicity was mild, and grade 3–4 adverse effects were mainly: neutropenia (9%), anemia (6%), asthenia/fatigue (7%) and constipation (5%).ConclusionsIn routine clinical practice the results obtained with VFL seem to be better than the results of the registration trial and reinforce evidence supporting its use after failure of a platinum-based chemotherapy.