Safety and clinical outcomes of patients treated with abiraterone acetate after docetaxel: results of the Italian Named Patient Programme.

OBJECTIVE: To assess the safety and efficacy of abiraterone acetate (AA) in patients with metastatic castration-resistant prostate cancer (mCRPC) treated in a compassionate named patient programme (NPP). PATIENTS AND METHODS: We retrospectively reviewed the clinical records of patients with mCRPC treated with AA at the standard daily oral dose of 1000 mg plus prednisone 10 mg/day in 19 Italian hospitals. RESULTS: We assessed 265 patients with mCRPC treated with AA. The most frequent (>1%) grade 3-4 toxicities were anaemia (4.2%), fatigue (4.2%), and bone pain (1.5%). The median progression-free survival was 7 months; median overall survival was 17 months after starting AA, and 35 months after the first docetaxel administration. Our study reproduced the clinical outcomes reported in the AA pivotal trial, including those relating to special populations such as the elderly, patients with a poor performance status, symptomatic patients, and patients with visceral metastases. CONCLUSIONS: Our data show the safety and activity of AA when administered outside clinical trials, and confirm the findings of the post-docetaxel pivotal trial in the patients as a whole population and in special populations of specific interest.

Synchronous Versus Metachronous Metastatic Disease: Impact of Time to Metastasis on Patient Outcome-Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

BACKGROUND: Patients with metastatic renal cell carcinoma (mRCC) may present with primary metastases (synchronous disease) or develop metastases during follow-up (metachronous disease). The impact of time to metastasis on patient outcome is poorly characterised. OBJECTIVE: To characterise overall survival (OS) and time to treatment failure (TTF) based on time to metastasis in mRCC patients treated with targeted therapy (tyrosine kinase inhibitors [TKIs]). DESIGN, SETTING, AND PARTICIPANTS: We used the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) to compare synchronous (metastases within ≤3 mo of initial diagnosis of cancer) versus metachronous disease (evaluated by >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr intervals). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: OS and TFF were assessed using Kaplan-Meier curves. Cox multivariable regressions analyses (MVAs) were adjusted for baseline factors. RESULTS AND LIMITATIONS: Of 7386 patients with mRCC treated with first-line TKIs, 3906 (53%) and 3480 (47%) had synchronous and metachronous metastasis, respectively. More patients with synchronous versus metachronous disease had higher T stage (T1-2: 19% vs 34%), N1 disease (21% vs 6%), presence of sarcomatoid differentiation (15.8% vs 7.9%), Karnofsky performance status <80 (25.9% vs 15.1%), anaemia (62.5% vs 42.3%), elevated neutrophils (18.9% vs 10.9%), elevated platelets (21.6% vs 11.4%), bone metastases (40.4% vs 29.8%), and IMDC poor risk (40.6% vs 11.3%). Synchronous versus metachronous disease by intervals >3-12 mo, >1-2 yr, >2-7 yr, and >7 yr correlated with poor TTF (5.6 mo vs 7.3, 8.0, 10.8, and 13.3 mo, p <  0.0001) and poor OS (median 16.7 mo vs 23.8, 30.2, 34.8, and 41.7 mo, p <  0.0001). In MVAs, the adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.98 (0.90-1.06), 0.81 (0.73-0.91), 0.74 (0.68-0.81), and 0.60 (0.54-0.67), respectively, for OS (p <  0.0001), and 1.00 (reference), 0.99 (0.92-1.06), 0.98 (0.90-1.07), 0.83 (0.77-0.89), and 0.66 (0.60-0.72), respectively, for TTF (p <  0.0001). Data were collected retrospectively. CONCLUSIONS: Timing of metastases after initial RCC diagnosis may impact the outcomes from targeted therapy in mRCC. PATIENT SUMMARY: We looked at the impact of the timing of metastatic outbreak on survival outcomes in kidney cancer patients treated with targeted therapy. We found that the longer time to metastatic development was associated with improved outcome.

Significance of neutrophil-to-lymphocyte ratio in Western advanced EGFR-mutated non-small cell lung cancer receiving a targeted therapy.

PURPOSE: Lung cancer is one of the leading causes of cancer-related death worldwide and, although targeted therapy with tyrosine kinase inhibitors has dramatically improved the rates of response and survival in advanced EGFR-mutated adenocarcinoma, the overall outcome remains unsatisfactory. Therefore, new prognostic factors, preferably simple, inexpensive, and easy to reproduce on a large scale, are needed. We performed a retrospective analysis of our database including 63 western Caucasian patients with advanced EGFR-mutated lung adenocarcinoma and receiving gefitinib, erlotinib, or afatinib as first- or second-line therapy. Several studies demonstrated a strong link between elevated neutrophil-to-lymphocyte ratio (NLR) and poor prognosis both in early and advanced stages of non-small-cell lung cancer (NSCLC). METHODS: From January 2011 to December 2015, 63 consecutive elegible patients with advanced EGFR-mutated NSCLC were included in this analysis from 5 institutions. The NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count and the cutoff value was determined according to the mean NLR level. RESULTS: Despite the small sample analyzed, we found that NLR has a prognostic role for progression-free survival (PFS) and overall survival (OS), reaching a statistically significant difference with a better PFS and OS in the lower NLR group. CONCLUSIONS: Pretreatment NLR seems to represent a reliable, simple, and easy to reproduce laboratory tool to predict outcome and response to cancer therapies in this setting of Western Caucasian patients with EGFR-mutated NSCLC.

Characterizing the outcomes of metastatic papillary renal cell carcinoma.

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer in ccRCC patients and the hazard ratio of death was 0.71 for ccRCC patients. No differences in PFS or ORR were detected between type I and II PRCC in this limited dataset. The median OS for type I pRCC was 20.0 months while the median OS for type II was 12.6 months (P = 0.096). The IMDC prognostic model was able to stratify pRCC patients into favorable risk (OS = 34.1 months), intermediate risk (OS = 17.0 months), and poor-risk groups (OS = 6.0 months). pRCC patient outcomes were inferior to ccRCC, even after controlling for IMDC prognostic factors. The IMDC prognostic model was able to effectively stratify pRCC patients.