Background The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7–6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3–4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab.

Aim of this study was to investigate for the presence of existing prognostic factors in patients with bone metastases (BMs) from RCC since bone represents an unfavorable site of metastasis for renal cell carcinoma (mRCC). Data of patients with BMs from RCC were retrospectively collected. Age, sex, ECOG-Performance Status (PS), MSKCC group, tumor histology, presence of concomitant metastases to other sites, time from nephrectomy to bone metastases (TTBM, classified into three groups: 5 years) and time from BMs to skeletal-related event (SRE) were included in the Cox analysis to investigate their prognostic relevance. 470 patients were enrolled in this analysis. In 19 patients (4%),bone was the only metastatic site; 277 patients had concomitant metastases in other sites. Median time to BMs was 16 months (range 0 − 44y) with Median OS of 17 months. Number of metastatic sites (including bone, p = 0.01), concomitant metastases, high Fuhrman grade (p < 0.001) and non-clear cell histology (p = 0.013) were significantly associated with poor prognosis. Patients with TTBM >5 years had longer OS (22 months) compared to patients with TTBM <1 year (13 months) or between 1 and 5 years (19 months) from nephrectomy (p < 0.001), no difference was found between these two last groups (p = 0.18). At multivariate analysis, ECOG-PS, MSKCC group and concomitant lung or lymph node metastases were independent predictors of OS in patients with BMs. Our study suggest that age, ECOG-PS, histology, MSKCC score, TTBM and the presence of concomitant metastases should be considered in order to optimize the management of RCC patients with BMs.

Clinically relevant bone metastases are a major cause of morbidity and mortality for prostate cancer patients. Distinct phenotypes are described: osteoblastic, the more common osteolytic and mixed. A molecular classification has been also proposed. Bone metastases start with the tropism of cancer cells to the bone through different multi-step tumor–host interactions, as described by the “metastatic cascade” model. Understanding these mechanisms, although far from being fully elucidated, could offer several potential targets for prevention and therapy. Moreover, the prognosis of patients is markedly influenced by skeletal-related events. They can be correlated not only with bone metastases, but also with “bad” bone health. There is a close correlation between osteoporosis—a skeletal disorder with decreased bone mass and qualitative alterations—and prostate cancer, in particular when treated with androgen deprivation therapy, a milestone in its treatment. Systemic treatments for prostate cancer, especially with the newest options, have improved the survival and quality of life of patients with respect to skeletal-related events; however, all patients should be evaluated for “bone health” and osteoporotic risk, both in the presence and in the absence of bone metastases. Treatment with bone-targeted therapies should be evaluated even in the absence of bone metastases, as described in special guidelines and according to a multidisciplinary evaluation.

De novo metastatic hormone-sensitive PC (mHSPC) accounts for 5–10% of all prostate cancer (PC) diagnoses but it is responsible for nearly 50% of PC-related deaths. Since 2015, the prognosis of mHSPC has slightly improved thanks to the introduction of new hormonal agents and chemotherapy combined with androgen deprivation therapy from the first-line setting. This review describes the current therapeutic opportunities for de novo mHSPC, focusing on potential molecular biomarkers identified in the main clinical trials that have modified the standard of care, the genomic features of de novo mHSPC, and the principal ongoing trials that are investigating new therapeutic approaches and the efficacy of a biomarker-guided treatment in this setting. The road toward personalized treatment for de novo mHSPC is still long, considering that the randomized clinical trials, which have furnished the basis of the current therapeutic options, stratified patients according to clinical criteria that did not necessarily reflect the biological rationale of the chosen therapy. The role of transcriptomic profiling of mHSPC as a predictive biomarker requires further validation, and it remains to be ascertained how the genomic variants detected in mHSPC, which are regarded as predictive in the castration-resistant disease, can be exploited in the mHSPC setting.

The pattern and prognostic factors of delayed nausea and vomiting induced by moderately emetogenic chemotherapy have not yet been adequately studied. Data are derived from a large and well defined population of patients studied to evaluate the efficacy and tolerability of granisetron, dexamethasone and their combination in the control of acute emesis over repeated cycles of moderately emetogenic chemotherapy. Patients were monitored on days 2–5 without receiving any prophylactic treatment for delayed emesis. There were 395 evaluable patients at the first, 352 at the second and 319 at the third cycle of chemotherapy. Overall, 32.7% patients suffered symptoms of delayed vomiting and/or moderate-severe nausea at the first, 32.1% at the second and 35.1% at the third cycle of chemotherapy. More precisely, the incidence of delayed vomiting was 21.3% at the first, 18.5% at the second and 21.0% at the third cycle of chemotherapy, while the incidence of delayed moderate-severe nausea was 25.1%, 25.0% and 26.0%, respectively. The incidence of delayed vomiting and moderate-severe nausea was very low in patients who obtained good control of acute vomiting and moderate-severe nausea, but it remained substantial in patients who experienced them during the first 24 hours after chemotherapy. In fact, at first/second/third cycle of chemotherapy delayed vomiting occurred in 12.3%/11.8%/ 13.1% of patients who did not suffer from acute vomiting and in 54.1%/48.4%/55.9% of those who had acute vomiting, respectively. Similar data were obtained for delayed moderate-severe nausea. Patients without acute vomiting or moderate-severe acute nausea may not need any antiemetic prophylaxis for delayed vomiting or nausea, while those with a history of acute vomiting or moderate-severe acute nausea should always be treated for delayed emesis. Selection bias and dependence effect of delayed emesis on acute emesis can cause misinterpretation of data derived from clinical trials in patients submitted to multiple cycles of chemotherapy.