Search

Background The taxanes docetaxel and cabazitaxel prolong overall survival for men with metastatic castration-resistant prostate cancer (mCRPC), with cabazitaxel approved in the postdocetaxel setting only. Recent data suggest they have similar efficacy but a different safety profile in the first-line mCRPC setting. Objective To assess patient preference between docetaxel and cabazitaxel among men who received one or more doses of each taxane and did not experience progression after the first taxane. Design, setting, and participants Chemotherapy-naive patients with mCRPC were randomized 1:1 to receive docetaxel (75 mg/m2 every 3 wk × 4 cycles) followed by cabazitaxel (25 mg/m2 every 3 wk × 4 cycles) or the reverse sequence. Randomization was stratified by prior abiraterone or enzalutamide use. Outcome measurements and statistical analysis The primary endpoint was patient preference, assessed via a dedicated questionnaire after the second taxane. Secondary endpoints included reasons for patient preference, prostate-specific antigen response, radiological progression-free survival, and overall survival. This clinical trial is registered at ClinicalTrials.gov as NCT02044354. Results and limitations Of 195 men randomized, 152 met the prespecified modified intent-to-treat criteria for analysis. Overall, 66 patients (43%) preferred cabazitaxel, 40 (27%) preferred docetaxel, and 46 (30%) had no preference (p = 0.004, adjusted for treatment period effect). More patients preferred treatment period 1 (43%, 95% confidence interval [CI] 36–52%) versus period 2 (27%, 95% CI 20–34%). Patient preference for cabazitaxel was mainly related to less fatigue (72%), better quality of life (64%), and other adverse events (hair loss, pain, nail disorders, edema). Adverse events were consistent with the known safety profile of each drug. Conclusions A significantly higher proportion of chemotherapy-naive men with mCRPC who received both taxanes preferred cabazitaxel over docetaxel. Less fatigue and better quality of life were the two main reasons driving patient choice. Patient summary Men with metastatic castration-resistant prostate cancer preferred cabazitaxel over docetaxel for chemotherapy, mainly because of less fatigue and better quality of life.

Few prognostic factors have been identified in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). The Lung Immune Prognostic Index (LIPI) was associated with clinical outcomes for ICIs in several tumor types. We aim to assess the value of the LIPI in patients with mUC treated with ICIs. A retrospective ICI cohort and a validation cohort (SAUL cohort) included, respectively, patients with mUC treated with ICI in 8 European centers (any line) and patients treated with atezolizumab in a second or further line. A chemotherapy-only cohort was also analyzed. The LIPI score was based on 2 factors, derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR) > 3 and lactate dehydrogenase > upper limit of normal, and defined 3 prognostic groups. The association of LIPI with progression-free survival (PFS) and overall survival (OS) was assessed. In the ICI and SAUL cohorts, 137 and 541 patients were respectively analyzed. In the ICI cohort, mPFS and mOS were 3.6 mo (95% CI; 2.6–6.0) and 13.8 mo (95% CI; 11.5–23.2) whereas in the SAUL cohort the mPFS and mOS were 2.2 mo (95% CI; 2.1–2.3) and 8.7 mo (95% CI; 7.8–9.9) respectively. The LIPI classified the population of these cohorts in good (56%; 52%), intermediate (35%; 36%) and poor (9%; 12%) prognostic groups (values for the ICI and SAUL cohorts respectively). Poor LIPI was associated with a poorer OS in both cohorts: hazard ratio (HR) for the ICI cohort = 2.69 (95% CI; 1.24–5.84, p = 0.035); HR = 2. 89 for the SAUL cohort (CI 95%: 1.93–4.32, p < 0.0001). Similar results were found in the chemo cohort. The LIPI score allows to identify different subgroups in patients with good prognostis according to the Bellmunt score criteria, with a subset of patients with poorer outcomes having an mOS of 3.7 mo compared to the good and intermediate LIPI subgroups with mOS of 17.9 and 7.4 mo, respectively. The LIPI score was associated with survival in mUC patients treated by ICIs. Future prospective studies will be required to test the combination of Bellmunt score and the LIPI score as a more accurate prognosis tool.

Background Cabazitaxel was shown to improve overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) after abiraterone/enzalutamine and docetaxel failure, though benefit by the presence of DNA damage repair (DDR) defects is unknown. With the advent of poly(adenosine diphosphate–ribose) polymerase inhibitors (PARPi) in partially overlapping indications with cabazitaxel, we aimed to determine cabazitaxel activity in men with mCRPC according to their DDR status. Methods This is a retrospective multicenter study that enrolled patients with mCRPC treated with cabazitaxel who had undergone DDR tumour tissue profiling. Patients with at least one deleterious germline or somatic alterations were considered DDR positive (DDR+). Each DDR + patient has been matched with a DDR negative (DDR-) from the same institution who underwent the same test. An exploratory cohort of patients found to be DDR + by liquid biopsy was also included. Prostate specific antigen (PSA) decline≥50% (PSA50), PSA progression-free survival (PFS, PSA-PFS), radiographic PFS (rPFS), clinical PFS or radiographic PFS (c/rPFS) and OS were evaluated. Results Among 190 men (95 DDR+, 95 DDR-) with tissue sequencing, PSA50 was achieved with cabazitaxel in 29/92 (32%) and 33/92 (36%) in patients with DDR+ and DDR- (P = 0.64). The median rPFS was 5.33 months [95%CI 4.34–7.04] versus 5.75 months [95%CI 4.67–7.27] (P = 0.55). The median OS was 15.4 months [95%CI 12.16–26.6] and 11.5 months [95%CI 9.76–14.4] (P = 0.036), respectively. No PSA50 responses on cabazitaxel were observed in BRCA1/2 patients previously treated with PARPi (n = 10). Similar outcomes with cabazitaxel were observed in the liquid biopsy cohort (n = 63 DDR+). Conclusions Our study suggests that cabazitaxel is active in patients with mCRPC regardless of their DDR status, although its activity in men pretreated with a PARPi may be lower.

Background Immune checkpoint inhibitor-based combination therapy (ICI-based combination) is a new standard of care for metastatic clear cell renal cell carcinoma (mRCC) in the frontline setting. Patients with poor performance status (PS) (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-based combination therapy in this group of patients is still unknown. Methods We performed a multicentre retrospective study of PS ≥2 mRCC patients who received frontline ICI-based combination, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (AP). Patients' characteristics, clinical outcomes, and toxicity were collected. We analysed overall response rate (ORR), median progression-free survival (mPFS), median overall survival (mOS) and grade ≥3 adverse events (G ≥ 3AEs). The association between the predictive biomarker IPI (immune prognostic index) and ORR/PFS/OS was also evaluated. Results We identified 70 mRCC patients with PS ≥2 treated with ICI-based combination across 14 institutions between October 2017 and December 2021, including 45 and 25 patients were treated with NI and AP, respectively. Median age at diagnosis was 63 years, 51 (73%) were male, only 17 (24%) had prior nephrectomy, 50 (71%) had synchronous metastatic disease at diagnosis, and 16 (23%) had brain metastases. Sixty-one (87%) and 9 (13%) patients had ECOG (Eastern Cooperative Oncology Group) PS 2 and 3, respectively, and 25 (36%) and 45 (64%) patients were intermediate and poor International Metastatic RCC Database Consortium (IMDC) risk, respectively. Among all, 91% were clear cell RCC, 7 patients had sarcomatoid features. At the time of the analysis (median follow-up 11.1 months), 41% patients were dead. Median PFS and mOS in the entire cohort were 5.4 months and 16.0 months, respectively; ORR was 31%. No significant differences in ORR, PFS, OS, or G ≥3AEs were seen between NI and AP. The intermediate and poor IPI groups were significantly associated with reduced ORR and shorter PFS. Conclusion We report the first cohort of PS ≥2 mRCC patients treated with frontline ICI-based combination therapy. The survival outcomes in our cohort were inferior to that reported in pivotal trials. No significant differences in ORR, PFS, OS or toxicity were seen between NI and AP. Prospective real-world studies are needed to confirm these results. pre-print 728 KB

International audience; Nivolumab and cabozantinib are approved agents in mRCC patients after sunitinib/pazopanib (TKI) failure. However, the optimal sequence, cabozantinib then nivolumab (CN) or nivolumab then cabozantinib (NC), is still unknown. The CABIR study aimed to identify the optimal sequence between CN and NC after frontline VEGFR-TKI. In this multicenter retrospective study, we collected data from mRCC pts receiving CN or NC, after frontline VEGFR-TKI. A propensity score (PrS) was calculated to manage bias selection, and sequence comparisons were carried out with a cox model on a matched sample 1:1. The primary endpoint was progression-free survival (PFS) from the start of second line to progression in third line (PFS2-3 ). Key secondary endpoints included overall survival from second line (OS2 ). Out of 139 included mRCC patients, 38 (27%) and 101 (73%) received CN and NC, respectively. Overlap in PrS allowed 1:1 matching for each CN pts, with characteristics well balanced. For both PFS2-3 and OS2 , NC sequence was superior to CN (PFS2-3 : HR = 0.58 [0.34-0.98], P = .043; OS2 : 0.66 [0.42-1.05], P = .080). Superior PFS2-3 was in patients treated between 6 and 18 months with prior VEGFR-TKI (P = .019) and was driven by a higher PFSL3 with cabozantinib when given after nivolumab (P

129 Background: The double-blind, phase 3, randomized KEYNOTE-921 trial (NCT03834506) showed that pembro + docetaxel did not significantly improve rPFS or OS for pts with mCRPC treated with prior next-generation hormonal agent (NHA) therapy. We present PROs for pembro + docetaxel vs placebo + docetaxel in KEYNOTE-921. Methods: Pts were randomly assigned 1:1 to receive pembro 200 mg or placebo IV Q3W (≤35 cycles) + docetaxel 75 mg/m2 IV Q3W (≤10 cycles) and prednisone 5 mg orally BID. PROs were evaluated in pts who received ≥1 dose of study treatment and had ≥1 PRO assessment. FACT-P and BPI-SF were administered at baseline, Q3W until wk 24, Q6W until wk 72, then Q12W for ≤2 y. A prespecified secondary end point was time to pain progression (TTPP) based on BPI-SF. Prespecified exploratory end points included least squares mean (LSM) change from baseline to wk 27 for FACT-P total and subscale scores (FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS) and wk 24 for BPI-SF scores (pain interference, pain severity, and worst pain), and time to deterioration (TTD) and overall improvement rate in FACT-P total and subscale scores. Differences were evaluated using 2-sided nominal P values not controlled for multiplicity. Results: Of 1030 pts enrolled, the PRO analysis population included 1028 (n = 514 in each arm). At the prespecified final analysis, median time from randomization to data cutoff of June 20, 2022, was 22.7 mo (range, 12.1-36.7). Completion rates for FACT-P and BPI-SF were >78% at baseline, >65% for FACT-P at wk 27, and >63% for BPI-SF at wk 24. Median TTPP was 21.1 mo (95% CI, 13.7-NR) for pembro + docetaxel vs NR (95% CI, 13.8-NR) for placebo + docetaxel (HR, 1.05 [95% CI, 0.77-1.43]). No LSM differences were observed in FACT-P total scores with pembro + docetaxel (–5.31 [95% CI, –7.02 to –3.61]) vs placebo + docetaxel (–3.89 [95% CI, –5.59 to –2.19]) or BPI-SF scores. Median TTD in FACT-P total scores was 21.8 mo (95% CI, 20.0-NR) for pembro + docetaxel and NR (95% CI, 11.1-NR) for placebo + docetaxel (HR, 1.09 [95% CI, 0.88-1.35]). No differences were observed for TTD in FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS scores between groups. A numerically lower proportion of pts receiving pembro + docetaxel (39.9%) had improved + stable FACT-P total scores compared with placebo + docetaxel (45.3%). FACT-P and BPI-SF scores were generally maintained across all evaluated time points up to wk 81. Conclusions: HRQoL and disease-related symptom scores at all analyzed time points, as well as TTD and TTPP, were similar between the 2 trial arms. These data suggest that pembro + docetaxel did not negatively impact QoL in pts with mCRPC treated with prior NHA. Clinical trial information: NCT03834506 . [Table: see text]

19 Background: Docetaxel is a treatment option following disease progression on a next-generation hormonal agent (NHA) for patients with mCRPC, but there is an urgent need for more efficacious treatments. The randomized, double-blind, phase 3 KEYNOTE-921 study (NCT03834506) evaluated the efficacy and safety of pembrolizumab + docetaxel vs placebo + docetaxel for participants (pts) with mCRPC who had received prior NHA therapy. Methods: Eligible pts were ≥18 years old, had mCRPC that progressed on androgen deprivation therapy, had received 1 prior NHA, and had an ECOG performance status of 0 or 1. Pts were randomized 1:1 to receive 200 mg pembrolizumab Q3W or placebo for ≤35 cycles (~2 years) in combination with 75 mg/m2 docetaxel Q3W for ≤10 cycles and 5 mg prednisone BID. The dual primary endpoints were radiographic progression-free survival (rPFS; tested at first interim analysis) per PCWG-modified RECIST 1.1 by blinded independent central review and overall survival (OS; tested at final analysis). The key secondary endpoint was time to initiation of the first subsequent anticancer therapy (TFST; at first interim analysis). Safety was one of the secondary endpoints. Results: Between May 30, 2019 and June 17, 2021, 1030 pts were randomized to receive pembrolizumab + docetaxel (n=515) or placebo + docetaxel (n=515). The median (range) time from randomization to data cutoff date of June 20, 2022 at final analysis was 22.7 mo (12.1−36.7). Baseline characteristics were generally balanced between arms; approximately half of pts in each arm had received prior abiraterone. Pts in the pembrolizumab + docetaxel arm received a median (range) of 12 (1–35) cycles of pembrolizumab and 9 (1–12) cycles of docetaxel; pts in the placebo + docetaxel arm received a median (range) of 12 (1–35) cycles of placebo and 9 (1–10) cycles of docetaxel. The dual primary endpoints of rPFS (median 8.6 mo with pembrolizumab + docetaxel vs 8.3 mo with placebo + docetaxel; HR 0.85, 95% CI 0.71−1.01; P=0.0335) and OS (median 19.6 mo vs 19.0 mo; HR 0.92, 95% CI 0.78−1.09; P=0.1677) were not met. Median TFST was 10.7 mo vs 10.4 mo, respectively (HR 0.86, 95% CI 0.74−1.01). Treatment-related AEs occurred in 94.6% (grade ≥3 in 43.2%) and 94.9% (grade ≥3 in 36.6%) of pts with pembrolizumab + docetaxel vs placebo + docetaxel. 2 treatment-related deaths with pembrolizumab + docetaxel and 7 with placebo + docetaxel were reported. Immune-mediated AEs and infusion reactions occurred in 23.3% (grade ≥3 in 6.2%) and 12.3% (grade ≥3 in 1.2%) of pts with pembrolizumab + docetaxel vs placebo + docetaxel, most commonly pneumonitis (7.0% vs 3.1%) and hypothyroidism (6.4% vs 3.3%). Conclusions: The addition of pembrolizumab to docetaxel did not significantly improve rPFS or OS for pts with mCRPC and did not result in a notable increase in treatment-related AEs. Clinical trial information: NCT03834506 .

Introduction. Immune checkpoint inhibitors (ICI) have been approved for front-line therapy in metastatic renal cell carcinoma (mRCC). However, progressive disease often occurs and subsequent therapies are needed. ICI rechallenge may be an option, but there is a lack of data regarding efficacy and prognostic factors. We assessed efficacy of ICI rechallenge and factors associated with better outcomes. Patients and Methods. This ambispective multicenter study included 45 mRCC patients rechallenged with nivolumab ± ipilimumab between 2014 and 2020. Primary endpoint was investigator-assessed best objective response rate (ORR) for ICI rechallenge (ICI-2). Factors associated with ICI-2 progression-free survival (PFS) were evaluated with multivariate Cox models. Results. ORR was 51% (n = 23) at first ICI therapy (ICI-1) and 16% (n = 7) for ICI-2. Median PFS was 11.4 months (95% CI, 9.8–23.5) and 3.5 months (95% CI, 2.8–9.7), and median overall survival was not reached (NR) (95% CI, 37.8–NR) and 24 months (95% CI, 9.9–NR) for ICI-1 and ICI-2, respectively. Factors associated with poorer ICI-2 PFS were a high number of metastatic sites, presence of liver metastases, use of an intervening treatment between ICI regimens, Eastern Cooperative Oncology Group performance status ≥2, and poor International Metastatic RCC Database Consortium score at ICI-2 start. Conversely, ICI-1 PFS >6 months was associated with better ICI-2 PFS. In multivariate analysis, there were only statistical trends toward better ICI-2 PFS in patients with ICI-1 PFS >6 months ( p = 0.07 ) and toward poorer ICI-2 PFS in patients who received a treatment between ICI regimens ( p = 0.07 ). Conclusion. Rechallenge with nivolumab-based ICI has some efficacy in mRCC. We identified various prognostic factors in univariate analysis but only statistical trends in multivariate analysis. Our findings bring new evidence on ICI rechallenge and preliminary but unique data that may help clinicians to select patients who will benefit from this strategy.

Despite recent advances, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) progressing after next-generation hormonal agents (NHAs) are limited and provide only modest survival benefit. Thus, an unmet need remains for mCRPC patients after treatment with targeted endocrine therapy or NHA therapy. Pembrolizumab, a humanized monoclonal antibody for PD-1, has been found to have activity as monotherapy in patients with mCRPC and as combination therapy in a Phase Ib/II study with docetaxel and prednisone/prednisolone for patients previously treated with enzalutamide or abiraterone acetate. The aim of the randomized, double-blind, Phase III KEYNOTE-921 study is to evaluate the efficacy and safety of pembrolizumab plus docetaxel in patients with mCRPC who were previously treated with an NHA. Clinical trial registration: NCT03834506 ( ClinicalTrials.gov )

Background Cabozantinib showed efficacy and manageable toxicity in patients with metastatic renal cell carcinoma (mRCC). In this study we aimed to describe the safety and to collect evidence on the potential efficacy of cabozantinib in mRCC patients with brain metastases (BM) in a real-world experience. Materials and Methods We retrospectively collected data of patients treated with cabozantinib within the Italian Managed Access Program. Patients were selected for the presence of BM before the start of treatment and for at least 1 previous tyrosine kinase inhibitor (TKI) treatment regimen for metastatic disease. Safety data were reported, and overall response rate (ORR), brain-specific response, progression-free survival (PFS), and median overall survival (OS) were analyzed. Results Overall, 12 patients treated with cabozantinib were evaluated. Any grade adverse events (AEs) accounted for 92%, Grade 3/4 AEs rated at 36% with no major neurological side effects. The most common AEs included hypertension (33%), fatigue (24%), aminotransferase elevation (25%), hypothyroidism (16%), and gastrointestinal toxicity (16%). The ORR was 50% with a disease control rate of 75%. All 5 patients treated with a combined systemic and brain-directed approach obtained intracranial disease control, without increased toxicity. Median PFS and median OS were 5.8 and 8.8 months, respectively. Comparable safety and tolerability results for other TKI regimens were reported from the literature. Conclusion Cabozantinib showed safety, acceptable tolerability, and promising antitumor activity in a population of mRCC patients with BM from a real-world experience. A combined modality approach for renal cell carcinoma with BM, whenever feasible, could be recommended to improve oncological outcomes.

Immunotherapeutic strategies have become the new paradigm of cancer care, through their new targeting and safety profile approach, and, de facto, their new monitoring and safety management challenges.Generalities and specificities of the toxicity management related to immune checkpoint inhibitors (ICIs) are highlighted. Predictive factors of safety are issue of research and the challenge of prevention as well as monitoring are huge to alleviate toxicities and enhance safety and efficacy. Particular situations like steroids association and cost-effectiveness approach are summarized.Patients as well as general practitioners, including health-caregivers, should be informed before ICI initiation of the different alert symptoms which should precede immune-related adverse events.

The activity of cabozantinib in nonclear cell histologies has not been evaluated.Data were collected across 24 Italian hospitals. Patients were aged 18 years and older with advanced nonclear cell renal cell carcinoma (RCC), with an Eastern Cooperative Oncology Group Performance Status 0 to 2, who had relapsed after previous systemic treatments for metastatic disease. Cabozantinib was administered orally at 60 mg once a day in 28 days cycles. Dose reductions to 40 or 20 mg were made due to toxicity. Adverse events (AEs) were monitored using CTCAE version 4.0.Seventeen patients were enrolled. Three (18%) patients were diagnosed type I papillary RCC, 9 (53%) type II papillary, 3 (18%) chromophobe, and 2 (11%) with Bellini duct carcinoma. In total, 11 patients started with 60 mg. Six patients started a lower dose of 40 mg. Median progression-free survival was 7.83 months (0.4 to 13.4 mo), while median overall survival was not reached but 1-year overall survival was about 60%. Six patients (35%) experienced a partial response to treatment and 6 patients (35%) showed a stable disease. In the remaining 5 (30%), we observed a progressive disease. Grade 3 and 4 AEs were observed in 41% of patients. Among 20 patients, only 1 (6%) discontinued treatment due to AEs. Asthenia (41%), diarrhea (35%), aminotransferase increasing (35%), mucosal inflammation (35%), hand and foot syndrome (24%), and hypothyroidism (24%) were the most frequently AEs.Our data showed that, cabozantinib is a active and feasible treatment in patient with nonclear cell RCC.

Metastatic prostate cancer is a poor prognosis condition that includes several different biological and clinical disease patterns. The cornerstone of treatment is androgen deprivation therapy (ADT), given the strict dependence of this tumor on androgens. The natural history of metastatic prostate cancer is characterized by two stages, according to tumor sensibility to hormonal therapy: hormone-sensitive disease (metastatic hormone-sensitive prostate cancer (mHSPC)) and castration-resistant disease (metastatic castration-resistant prostate cancer (mCRPC)). Chemotherapy with taxanes (docetaxel and cabazitaxel), second-generation hormonal therapies (abiraterone and enzalutamide), and particle-emitting radionuclides (radium-223) represent different therapeutic options for metastatic disease.

Background: Cabozantinib strongly inhibits osteoclast differentiation and bone resorption in vitro. We aimed to evaluate its effect on bone turnover markers (BTMs) in metastatic renal cell carcinoma. Methods: This is a monocentric prospective study on patients with mRCC treated with cabozantinib between October 2016 and July 2018. We collected blood samples at baseline and after 3 and 6 months of treatment. We compared sets of data obtained from plasma samples in the whole population with unpaired 2-tailed Student t tests and data for a subset of patients for which all timepoints were available with paired 2-tailed Student t tests. We used the Kaplan-Meier method for survival analyses and the log-rank test to compare the curves. Results: Our analysis included 39 patients. At month 3, the mean C-terminal cross-linked telopeptides of type I collagen (CTx) and the mean N-terminal propeptide of type 1 collagen (PINP) levels were significantly decreased in the whole population ( p = 0.013 and p < 0.0001, respectively), as well as at paired analysis ( p = 0.015 and p = 0.045, respectively). No differences were observed between baseline and 6 months ( p = 0.053 and p = 0.087, respectively). After 3 months, the mean parathyroid hormone (PTH) levels significantly increased in the whole population ( p = 0.004), as well as at paired analysis; the mean PTH levels increased significantly at 3 and 6 months, respectively ( p = 0.019 and p = 0.041, respectively). Changes in BTM levels were not associated with outcome. Conclusions: Cabozantinib significantly reduced bone resorption as demonstrated by the decrease of CTx and showed a transient secondary increase of PTH.

Background: Cancer is considered as a crucial risk factor for adverse outcomes from coronavirus disease 2019 (COVID-19) There is currently few data available about the impact of the virus on patients (pts) treated for cancer, mainly coming from Comprehensive Cancer Centres In April 2020, the Italian Medical Council reported an analysis on 909 pts who died from COVID-19, of whom 16 5% had cancer Recently, Gustave Roussy Institute in Paris published a series of 137 cancer patients presenting COVID-19 Here, we report our experience in Foch Hospital in Paris, an academic general hospital located in one of the two main epicentres of the epidemic in France Methods: We analysed the totality of pts diagnosed with COVID-19 in our hospital including the emergency unit, as well as the pts currently treated for cancer in our two Medical Oncology and Pulmonology departments Results: We identified 49 pts presenting COVID-19 from March 2nd until May 11th 2020 All of them were receiving standard medical treatment and care for cancer, in curative and palliative settings Median age was 68 years Eastern Cooperative Oncology Group (ECOG) Performance Status was respectively: 0-1 (67%), 2-3 (31%), 4(2%) Twenty-two percent of pts were in curative situation and 78% in palliative situation Twenty-one (43%), 12 (25%), 8 (16%) and 3 (6%) pts had a lung, genitourinary, gastro-intestinal and head and neck cancer respectively Moreover, 2 (4%), 2 (4%) and 1 (2%) pts had a breast, gynaecological and mesothelioma cancer respectively Six percent of pts presented severe disease needing treatment in intensive care unit Global mortality rate was 22% Eight percent of our pts were receiving immunotherapy, and none of these presented a serious clinical presentation At the hospital level, cancer patients represented 7 8% of the subjects with a diagnosis of COVID-19, 5% of patients hospitalized, and 3% of patients in intensive care unit Thirteen percent of patients who died had a cancer Conclusions: COVID-19 greatly impacted old and fragile patients The results of our cohort are comparable to the data reported in a Comprehensive Cancer Centre of Paris area It is also remarkable that pts treated with immunotherapy seem to present a less severe disease, without any patient needing intensive care Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest

Circulating tumor cells (CTCs) are promising biomarkers for prognosis, therapeutic response prediction, and treatment monitoring in cancer patients. Despite its epithelial origin, renal cell carcinoma (RCC) shows low expression of epithelial markers hindering CTC-enrichment approaches exploiting epithelial cell surface proteins. In 21 blood samples serially collected from 10 patients with metastatic RCC entering the TARIBO trial, we overcame this limitation using the marker-independent Parsortix&trade, approach for CTC-enrichment coupled with positive and negative selection with the DEPArray&trade, with single cell recovery and analysis for copy number alterations (CNA) by next generation sequencing NGS. Two CTC subpopulations were identified: epithelial CTC (eCTC) and non-conventional CTC (ncCTC) lacking epithelial and leukocyte markers. With a threshold &ge, 1CTC/10 mL of blood, the positivity rates were 28% for eCTC, 62% for ncCTCs, and 71% considering both CTC types. In two patients with detectable eCTCs at baseline, progression free survival was less than 5 months. In an index case, hierarchical structure by translational oncology (TRONCO) identified three clones among 14 CTCs collected at progression and at baseline, each containing cells with a 9p21.3loss, a well-known metastasis driving subclonal alteration. CTCs detection in RCC can be increased by marker-independent approaches, and CTC molecular characterization can allow detection of subclonal events possibly related to tumor progression.

320 Background: Immune checkpoint combination therapy (ICI-combo) is the new standard of care for mRCC in first-line setting. However, pts with poor PS (≥2) were excluded from pivotal trials. Hence, the activity and safety of ICI-combo in this group of pts is still unknown. Methods: We performed a multicentre retrospective study of PS≥2 mRCC pts who received ICI-combo, either nivolumab-ipilimumab (NI) or pembrolizumab-axitinib (PA) as first-line treatment between 2017-2021. Patient’s characteristics, clinical outcomes and toxicity were retrospectively reviewed. We analysed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and grade ≥3 treatment-related adverse events (G≥3 AEs) in pts treated with NI or PA. The association between LIPI (Lung Immune Prognostic Index) and ORR, PFS and OS was also evaluated. Results: We identified 56 mRCC pts with PS≥2 treated with ICI-combo across 13 institutions. Thirty-six and 20 pts were treated with NI and PA respectively. Median age at diagnosis was 64 (31-83) years, 38 (68%) were male, 16 (29%) had prior nephrectomy and 40 (71%) had synchronous metastatic disease at diagnosis. Respectively, 19 (34%) and 37 (66%) pts were intermediate and poor risk according to IMDC. Fifty pts (89%) were clear cell RCC, and only 4 pts had sarcomatoid features reported. At the time of analysis (median follow-up 11.1 months(mo)) 45% pts were dead. The ORR for the entire cohort was 27%; ORR was numerically higher with PA (42%) than with NI (20%) but did not reach statistical significancy (p=0.157). Median PFS (mPFS) and mOS in the entire cohort were 4.4 mo and 15.9 mo respectively. No significant differences in PFS, OS or the rate of G≥3AEs were seen between the NI and PA groups. Efficacy and toxicity outcomes are described in the table below. No significant differences in OS or PFS according to the IMDC risk score were observed (p=0.818). However, LIPI was significantly associated with OS (poor LIPI: HR=8.18; p=0.004) and PFS (Intermediate LIPI: HR=2.4; p=0.048 and poor LIPI: HR=8.59; p

Purpose: Two randomized trials in the cytokine era showed that cytoreductive nephrectomy (CN) had a role in metastatic renal cell carcinoma (mRCC), increasing life expectancy. The survival benefit of tyrosine kinase inhibitors (TKIs), including first-line sunitinib and pazopanib, in mRCC has been demonstrated, but the majority of patients enrolled in the pivotal phase III studies had undergone nephrectomy. Therefore it is unknown if similar survival benefit with targeted agents could be achieved without CN. We hypothesize that in these patients CN could increase overall survival (OS) in comparison to targeted therapy without CN. We also will investigate mechanisms of primary and secondary resistance to TKIs in patients with mRCC and identify prognostic or predictive biomarkers. Methods: This is a randomized, open-label, controlled, multicenter phase 3 study comparing sunitinib or pazopanib vs CN followed by sunitinib or pazopanib as first-line therapy for patients with mRCC who have not received surgery and prior systemic treatment for metastatic disease. We will identify 270 patients eligible for randomization. The planned treatment duration per patient will be until progressive disease is observed. Secondary endpoints are the evaluation of progression-free survival (PFS) and response rate and the assessment of the safety profile. Exploratory objectives include the evaluation of circulating tumor cells and circulating tumor DNA and correlation with response/resistance to treatment. Results: The study is enrolling patients. Conclusions: The use of CN in addition to targeted therapy in patients with renal cell carcinoma with synchronous metastases could lead to a significant improvement in OS and PFS.

Background: Abiraterone acetate became a referral treatment for metastatic castration-resistant prostate cancer (mCRPC) in a post-docetaxel setting despite a remarkable percentage of cardiovascular adverse events (AEs). As a consequence, the evaluation of cardiovascular safety in patients at risk should be mandatory. We aimed to assess the cardiovascular safety of abiraterone acetate in a real-world series of mCRPC patients treated at our institution. Materials and Methods: We retrospectively included mCRPC patients with at least 1 active cardiovascular comorbidity or risk factor according to the European Society of Cardiology (ESC) guidelines and who started treatment with abiraterone acetate from April 2011 to July 2012. Cardiac assessment with electrocardiogram and echocardiogram was performed at baseline and at treatment discontinuation. AEs were defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Statistical analyses were performed by descriptive statistics as appropriate. Results: We included 51 patients of whom 18% had an ESC score risk for a major cardiovascular event ≥4%. At a median follow-up of 36 months, no cardiac AEs (rhythm abnormalities or left ventricular function decrease) were observed. The most frequent grade 1-2 AE reported was fluid retention (18%) followed by hypertension and asthenia (16%). The most frequent grade 3-4 AEs were asthenia and pruritus/rash. No patients discontinued abiraterone because of toxicity. Conclusions: Abiraterone acetate showed a favorable safety profile in mCRPC patients with cardiovascular comorbidities or risk factors in a post-docetaxel setting, but further studies are needed to confirm our findings and to explore other settings of disease.

Renal cell carcinoma (RCC) is considered an immunogenic tumor with a prominent dysfunctional immune cell infiltrate, unable to control tumor growth. Cytokine-based immunotherapies, including interferon-α and interleukin-2, have been used for the treatment of metastatic RCC (mRCC). Long-term responses and complete remissions were observed, but durable clinical benefit efficacy in the overall population was limited and associated with significant toxicity. As a consequence, new generation agents targeting the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways replaced interferon alpha (IFN-α). Strategies of tumor immune evasion include T-cell suppression by negative signals deriving from the interaction between programmed death-1 (PD-1) on the T cell and its ligand (PDL-1) on the tumor cells. Nivolumab, a programmed death 1 checkpoint inhibitor, blocks this pathway, thus reversing T-cell suppression and activating antitumor responses. The aim of this review is to summarize the safety and efficacy data of nivolumab in mRCC. Objective responses and safety profile of single-agent nivolumab are favorable in both previously treated and treatment-naïve mRCC patients. Despite toxic effects, combination therapies with nivolumab have shown promising results, indicating a potential role in the treatment of mRCC. Tailoring immunotherapy on a patient-to-patient basis represents a major challenge for the future.

The treatment of metastatic renal cell carcinoma (mRCC) has markedly improved over the last few years with the introduction of several targeted agents in clinical practice. Nevertheless, either primary or secondary resistance to inhibition of VEGF and mTOR pathways has limited the clinical benefit of these systemic treatments. Recently, a better understanding of the involvement of MET and its ligand HGF in many biological processes made this signaling pathway an attractive therapeutic target in oncology, particularly in mRCC. Herein, we review the development of cabozantinib, a recently approved inhibitor of multiple tyrosine kinase receptors, including MET, VEGFRs, and AXL, which has proven to increase progression-free survival and overall survival when compared to everolimus in mRCC patients who had progressed after VEGFR-targeted therapy. Finally, we discuss the potential role of cabozantinib within the current treatment landscape for mRCC.

// Daniele Santini 1 , Raffaele Ratta 2 , Francesco Pantano 1 , Delia De Lisi 1 , Marco Maruzzo 3 , Luca Galli 4,6 , Elisa Biasco 4 , Azzurra Farnesi 4 , Sebastiano Buti 5 , Cora Nanette Sternberg 6 , Linda Cerbone 6 , Giuseppe Di Lorenzo 7 , Silvia Spoto 8 , Michelle Sterpi 1 , Ugo De Giorgi 9 , Rossana Berardi 10 , Mariangela Torniai 10 , Andrea Camerini 11 , Francesco Massari 12 , Giuseppe Procopio 2 and Giuseppe Tonini 1 1 Campus Bio-Medico University of Rome, Department of Medical Oncology, Rome, Italy 2 Fondazione IRCCS, Istituto Nazionale dei Tumori, Oncology Unit 1, Milan, Italy 3 Istituto Oncologico Veneto, IOV-IRCCS, Medical Oncology 1 Unit, Padova, Italy 4 University Hospital of Pisa, Oncology Unit 2, Pisa, Italy 5 University Hospital of Parma, Medical Oncology, Parma, Italy 6 San Camillo and Forlanini Hospitals, Department of Medical Oncology, Rome, Italy 7 Department of Clinical Medicine & Surgery, Oncology Division, University Federico II, Naples, Italy 8 Campus Bio-Medico University of Rome, Department of Internal Medicine, Rome, Italy 9 IRCCS Istituto Scientifico Romagnolo per lo studio e la Cura dei Tumori, Department of Medical Oncology, Meldola, Italy 10 Universita Politecnica delle Marche, Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, Medical Oncology Unit, Ancona, Italy 11 Versilia Hospital and Istituto Toscano Tumori, Medical Oncology, Lido di Camaiore, Italy 12 S.Orsola-Malpighi Hospital, Division of Oncology, Bologna, Italy Correspondence to: Delia De Lisi, email: // Keywords : metastatic renal cell carcinoma (mRCC), oligoprogression, pazopanib, sunitinib, targeted therapy Received : April 25, 2016 Accepted : June 19, 2017 Published : August 07, 2017 Abstract Locoregional treatment with radical intent should be considered during therapy with targeted agents in patients with metastatic renal cell carcinoma (mRCC) in order to achieve a complete response, especially in the setting of an oligo-progression in one or more metastatic sites. We retrospectively enrolled 55 patients who experienced a disease oligo-progression after at least 6 months from the beginning of first-line therapy in one or more metastatic sites radically treated with locoregional treatments. Post-first-oligo-progression overall survival (PFOPOS) and post-first-oligo-progression free survival (PFOPFS) were evaluated. The global median PFOPOS and PFOPFS were 37 months and 14 months respectively. Patients who continued the same therapy after a locoregional treatment on a site of progression had a significantly longer mPFOPOS compared to patients who changed therapy (39 vs 11 months, p =0.014). An advantage in mPFOPOS was also observed in patients with a Memorial Sloan-Kettering Cancer Center (MSKCC) good risk score compared to patients of the intermediate risk group (39 vs 29 months, p =0.036); patients with bone metastases had a longer mPFOPOS compared to those with visceral metastases (not reached vs 31 months, p =0.045). The only independent predictor of poor prognosis, in terms of PFOPOS at multivariate analysis ( p =0.007), proved out to be change of treatment after first progression. In this paper we aim to illustrate that continuing the same systemic therapy, after a radical locoregional treatment on a site of progression, seems to be associated with a prolongation of mPFOPOS.

Background Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear. Objectives Our objective was to conduct a retrospective analysis to investigate the clinical effect of different therapeutic doses of first-line pazopanib in patients with mRCC. Methods Consecutive patients with mRCC treated with first-line pazopanib between 2011 and 2016 at the Istituto Nazionale Tumori of Milan were retrospectively analysed for demographics, response, outcomes, and toxicity. Three patient groups were compared: group 1 received the standard dose of 800 mg/day; group 2 started with 800 mg/day and then reduced the dose to 400 or 600 mg/day because of toxicity; and group 3 received a reduced starting dose of 400 or 600 mg/day because they had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and/or comorbidities. Results In total, 69 patients were evaluated: 34 in group 1, 19 in group 2, and 16 in group 3. After a median follow-up of 13.9 months (range 0.3–43.8), 27 (39.1%) patients had progressive disease (PD) and three (4.3%) patients had died. The incidence rate of PD or death per 100 person-months was 2.5 [95% confidence interval (CI) 0.6–4.4; hazard ratio (HR) 1] in group 1 and 3.9 (95% CI 0–14.3; HR 1.43) in the combined group (2 + 3). The discontinuation rate due to PD was 28% in group 1, 42% in group 2, and 44% in group 3. The objective response rate was 44, 11, and 19% in groups 1, 2, and 3, respectively. Conclusions Our results may suggest that patients with mRCC receiving a lower dose of first-line pazopanib might not have a meaningful progression-free survival advantage compared with those receiving a standard dose. These data highlight that proper management of treatment-related side effects may lead to optimal drug exposure.

Renal cell carcinoma (RCC) is the ninth most common cancer in humans. In the last decade, a better understanding of the molecular mechanisms underlying tumorigenesis, angiogenesis, cell growth and proliferation, and the discovery of molecular alterations involved in RCC pathogenesis, have led to the identification of molecular targets of great clinical interest that have revolutionized the treatment of metastatic RCC (mRCC). Sunitinib, pazopanib and bevacizumab plus interferon-alpha remain the standard first-line treatments: these agents have significantly improved prognosis in mRCC. Everolimus, axitinib and sorafenib have demonstrated significant efficacy as second-line therapies. Nivolumab and cabozantinib are the most promising new-generation agents in the treatment of RCC. All of these agents, given in sequence, have extended life expectancy of RCC patients from 13 months in the cytokine era to over 20 months. Despite this improvement, it is not easy to establish the right sequence in which to administered different agents because there aren’t yet ways to identify or select patients likely to benefit or those who could be resistant to specific drugs. In this review we present clinical data on the sequential treatment in RCC and discuss key factors that need to be considered when physicians make treatment decisions for individual patients.

A great number of DNA-damage repair (DDR) pathways have been recognized to be frequently dysregulated in advanced stages of prostate cancer. DNA-repair defects in prostate cancer represents a clinically relevant disease subset. Tumors whose ability to repair double-strand DNA breaks by homologous recombination is compromised, are highly sensitive to blockade of the repair of DNA single-strand breaks via the inhibition of the enzyme poly(ADP) ribose polymerase (PARP). A systematic review of the literature has been conducted in January 2020 using PubMed Medline database in line with the recommendations from the PRISMA guidelines. The following string terms were used for searching clinical trial articles: castration resistant OR castrate resistance OR castration refractory AND prostate cancer AND PARP OR poly(ADP-ribose) polymerase inhibitor OR DNA-repair OR homologous recombination repair. On-going clinical trials with olaparib, niraparib, talazoparib, veliparib, and rucaparib in mCRPC were searched on the clinicalTrials.gov website. From this research 176 articles were identified. After title screening and abstract reading, five papers and four abstract were considered for the systematic review. Thirty-two clinical trials were also identified: from these 16 trials which did not include mCRPC patients or only prostate cancer patients, trials not yet recruiting and trials including radio-metabolic treatments were excluded. Sixteen trials were included and discussed in the paper. Olaparib has been the first agent showing a benefit in terms of rPFS and ORR alone or in combination with abiraterone plus prednisone in patients with DDR deficiency prostate cancer. Also rucaparib showed a benefit in terms of PSA response rate and ORR in patients with BRCA2 and BRCA1 mutation in a phase-II study. Other phase-III clinical trials are evaluating niraparib and talazoparib, alone or in combination with AR signaling inhibitors.

Background In selected metastatic renal cell carcinoma (mRCC) patients, radical metastasectomy followed by observation is a potential strategy. It is still to be defined whether systemic therapy should be administered following metastasectomy. Objective To assess the potential benefit of postoperative treatment with sorafenib compared with observation alone after radical metastasectomy in mRCC patients. Design, setting, and participants The RESORT trial was a multicenter, randomized, open-label, phase 2 study conducted between November 2012 and November 2017 in Italy. Patients with clear-cell mRCC pretreated with nephrectomy and undergoing radical metastasectomy (three or fewer lesions) were eligible for the study. Patients were randomized (1:1) within 12 wk from metastasectomy to sorafenib (standard dose 400 mg twice daily) or observation for a maximum of 52 wk. Stratification factors were interval from nephrectomy, site, and number of lesions. Overall, 76 patients were screened and 69 were randomized: 33 were assigned to sorafenib and 36 to observation. The primary endpoint was recurrence-free survival (RFS). Secondary endpoints were overall survival and the safety profile. Outcome measurements and statistical analysis RFS curves were estimated with the Kaplan-Meier method, and the log-rank test was used to statistically compare the curves. Results and limitations At a median follow-up of 38 mo, median RFS was 37 mo (95% confidence interval [CI] 20–not available [NA]) in the observation arm versus 21 mo (95% CI 11–NA) in the sorafenib arm (log-rank test p = 0.404), with 12-, 24-, and 36-mo RFS probability of 74% versus 63%, 59% versus 49%, and 50% versus 41%, respectively, in the observation versus the sorafenib arm. Any-grade adverse event (AE) rates were 84% in the sorafenib arm and 31% in the observation arm; grade ≥3 AE rates were 22% and 3% in the sorafenib and the observation arm, respectively, with a rate of treatment discontinuation for AEs of 19% in the sorafenib arm. Conclusions This prospective study showed that systemic treatment with sorafenib did not increase RFS as compared with observation in mRCC patients following radical metastasectomy. Patient summary This article reports the clinical outcome of patients with metastatic renal cell carcinoma treated with sorafenib or managed with an observation-alone strategy after the radical surgery of metastases. We found that sorafenib did not improve the patient outcome in terms of relapse-free survival in this selected population.

Predictive biomarkers of response to immune-checkpoint inhibitors (ICIs) are an urgent clinical need. The aim of this study is to identify manageable parameters to use in clinical practice to select patients with higher probability of response to ICIs. Two-hundred-and-seventy-one consecutive metastatic solid tumor patients, treated from 2013 until 2017 with anti- Programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) ICIs, were evaluated for baseline lactate dehydrogenase (LDH) serum level, performance status (PS), age, neutrophil-lymphocyte ratio, type of immunotherapy, number of metastatic sites, histology, and sex. A training and validation set were used to build and test models, respectively. The variables&rsquo, effects were assessed through odds ratio estimates (OR) and area under the receive operating characteristic curves (AUC), from univariate and multivariate logistic regression models. A final multivariate model with LDH, age and PS showed significant ORs and an AUC of 0.771. Results were statistically validated and used to devise an Excel algorithm to calculate the patient&rsquo, s response probabilities. We implemented an interactive Excel algorithm based on three variables (baseline LDH serum level, age and PS) which is able to provide a higher performance in response prediction to ICIs compared with LDH alone. This tool could be used in a real-life setting to identify ICIs in responding patients.

Introduction: So far, clinical experiences have proved metastasectomy as the only approach in the setting of metastatic renal cell carcinoma that may achieve the 'no evidence of disease' status, with an associated improvement in survival. Areas covered: This review aims to summarize the body of knowledge on therapeutic approaches to mRCC, with a specific insight on the role of metastasectomy and on which underlying factors could be good predictors to select patients who may benefit from surgery. In detail, we managed to identify as potential selection criteria: the number of lesions and their site, the DFI, patients' performance status and, most of all, the completeness of resection. Expert opinion: The definition of the optimal treatment strategy of mRCC patients is still an unmet clinical need. The decision-making process about treatment strategy should consider specific tumor's and patient's characteristics, as well as the integration of the available therapeutic approaches with the aim to reach the best clinical outcome. We consider multidisciplinary management mandatory in order to tailor the treatment approach according to the patient and disease features. The experience of clinicians may be considered crucial in order to select the best candidates for a multimodal approach.

In recent years, several agents targeting the vascular endothelial growth factor, such as sunitinib, sorafenib, pazopanib, axitinib, and bevacizumab, and mammalian target of rapamycin pathways, including temsirolimus and everolimus, have been approved for the treatment of metastatic renal cell carcinoma (RCC). The lack of significant response to chemotherapy and the identification of immunologic dysfunctions have led to the development of different immunotherapeutic approaches in the past years. In recent years, a deep interest in immunotherapies in RCC has been observed, probably due to many improvements in the understanding of immune-escape strategies of cancer. Several phase I–III trials have demonstrated the immunologic involvement of RCC.

Metastatic renal cell carcinoma (mRCC) is a fatal urological cancer which represents the seventh most common site for tumors, causing more than 140,000 deaths per year worldwide [1].The past decade...

The frontline treatment options for patients with metastatic renal cell carcinoma (mRCC) are evolving rapidly since the approval of combination immunotherapies by the U.S. Food and Drug Administration (USFDA) and the European Medicines Agency (EMA). In particular, in combination with vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs) have significantly improved the outcome of patients with mRCC compared to TKI monotherapy. Here, we review the preclinical data supporting the combination of ICIs with VEGFR TKIs. The VEGF-signaling inhibition could ideally sustain immunotherapy through a positive modulation of the tumor microenvironment (TME). Antiangiogenetics, in fact, with their inhibitory activity on myelopoiesis that indirectly reduces myeloid-derived suppressor cells (MDSCs) and regulatory T cells’ (Tregs) frequency and function, could have a role in determining an effective anti-tumor immune response. These findings are relevant for the challenges posed to clinicians concerning the clinical impact on treatment strategies for mRCC.

TPS262 Background: Docetaxel is an established treatment for pts with mCRPC. Pembro, a PD-1 inhibitor, showed single-agent antitumor activity in mCRPC. In the phase 1b/2 KEYNOTE-365 study (NCT02861573), docetaxel + pembro and prednisone showed activity in pts treated with abi or enza for mCRPC, warranting further evaluation. Methods: KEYNOTE-921 (NCT03834506) is a phase 3 trial to evaluate efficacy and safety of pembro + docetaxel and prednisone in chemotherapy-naive pts who progressed with enza or abi therapy for mCRPC. An estimated 1000 pts will be randomly assigned 1:1 to receive docetaxel 75 mg/m2 IV every 3 weeks (Q3W) + prednisone/prednisolone orally 5 mg twice daily (BID) and pembrolizumab 200 mg IV Q3W or docetaxel 75 mg/m2 IV Q3W + prednisone/prednisolone 5 mg orally BID + placebo IV Q3W. Treatment will be stratified by previous next-generation hormone agent (abi or enza) and metastases location (bone only, liver, other). Adults (≥18 years) with histologically or cytologically confirmed mCRPC who progressed with androgen deprivation therapy (or postbilateral orchiectomy) ≤6 months of screening, have ECOG PS 0 or 1, and have adequate organ function are eligible. Pts must have experienced either progression after ≥8 weeks (≥14 weeks for bone progression) or intolerance after ≥4 weeks of abi or enza (but not both) in a chemotherapy-naive mCRPC state. Pts will be required to provide tissue for biomarker analysis. Responses will be assessed by CT or MRI and radionuclide bone imaging per Prostate Cancer Working Group 3 (PCWG3)–modified RECIST v1.1 by blinded independent central review (BICR) Q9W during the first year and Q12W thereafter. Treatment will continue with docetaxel and prednisone for up to 10 cycles and with pembro for up to 35 cycles or until disease progression, unacceptable toxicity, or consent withdrawal. Primary end points are rPFS by BICR and OS. Secondary end points are time to initiation of subsequent anticancer therapy or death, PSA response rate, time to PSA progression, ORR and DOR per PCWG3-modified RECIST v1.1 assessed by BICR, and safety. Accrual began May 2, 2019. Clinical trial information: NCT03834506.

545 Background: Prognostic factors for survival in metastatic urothelial carcinoma (mUC) have been reported in patients (pts) treated with chemotherapy (Bellmunt and al, JCO 2010). However, no biomarkers have been clearly identified in the setting of immune-checkpoint inhibitors (ICI). The Lung immune prognostic index (LIPI) was associated with clinical outcomes for ICI in lung cancer (Mezquita et al, Jama Oncol 2018) and other tumor types (Varga et al, TAT 2019). In this multicenter retrospective study, we correlated LIPI with outcomes in pts with mUC treated with ICI. Methods: Pts with mUC enrolled from May 2013 to July 2018 in 7 high volume centers were analysed. LIPI score includes: LDH > upper limit of normal and neutrophil/[leukocytes minus neutrophils] ratio (dNLR) > 3. The following LIPI subgroups were defined: good prognosis (0), intermediate prognosis (1) and poor prognosis (2 factors). Median (m) progression-free survival (PFS) and median overall survival (OS) were calculated using Kaplan-Meier method, log rank test was used for statistical comparison. Cox model was used for multivariate analysis. Results: To date, 152 mUC pts have been enrolled and preliminary analysis have been performed in 135 pts. Median age was 67 years, 111 (82%) pts were male, 106 pts (79%) had ECOG PS 0-1, 31 pts (23%) had liver metastasis. Median follow-up was 21.1 months (mo) (95% CI; 16.3-24.5), mPFS was 3.6 mo (95% CI; 2.6-6.0) and mOS was 13.8 mo (95% CI; 11.5-23.2). LIPI classified the population in good (56%), intermediate (35%) and poor (9%) prognosis group. In multivariate analysis, estimated mPFS in good, intermediate and poor prognosis were 5.8 mo (95% CI; 2.6-6.0), 3.6 mo (95% CI; 3.3-16.2) and 1.2 mo (95% CI;0.1-NR), respectively (p = 0.001). Estimated mOS in good, intermediate and poor prognosis were 17.3 mo (95% CI; 13.0-36.8), 16.9 mo (95% CI; 6.9-NR) and 5.4 mo (95% CI;2.5-NR), respectively (p = 0.19). OS data will be validated on larger cohort. Conclusions: The LIPI score is associated with clinical outcome to ICI and may be a useful tool for identifying patients who may not benefit from ICI. Validation in independent prospective cohort is ongoing.

Objectives: stereotactic body radiation therapy (SBRT) use has increased overtime for the management of metastatic renal cell carcinoma (mRCC) patients, with a likely good control of irradiated lesions. We planned a retrospective multicenter Italian study, with the aim of investigating the outcome of treatment with SBRT for non-brain secondary lesions in mRCC patients. Methods: all consecutive metastatic non-brain lesions from mRCC that underwent SBRT at nine Italian institutions from January 2015 to June 2017 were considered. The primary endpoint of the study was the lesion-PFS, calculated from SBRT initiation to the local progression of the irradiated lesion. Results: 57 extracranial metastatic lesions from 48 patients with primary mRCC were treated with SBRT. At the median follow-up of 26.4 months, the median lesion-PFS was not reached (43 censored); 72.4% of lesions were progression-free at 40 months, with significantly better lesion-PFS for small metastatic lesions (

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016–2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23–4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77–31.14; p

Background The purpose of the present retrospective analysis was to describe the trends in exposure to multiple lines of treatment and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) who started therapy in 2 different periods (period 1, 2004-2010; and period 2, 2011-2017). Patients and Methods The proportion of patients who received subsequent lines of treatment after disease progression was compared between the 2 groups. OS was measured from the start of first-line treatment for metastatic disease to death or the last follow-up examination. Both univariate and multivariate analyses were performed. Results A total of 500 patients were included in the study; 274 started treatment in period 1 and 226 in period 2. Of those patients who stopped first-line treatment because of disease progression, the patients in period 2 had a greater conditional probability to receive second- and third-line treatment compared with patients in period 1 (77.2% vs. 63.7%; odds ratio [OR], 1.93; 95% confidence interval [CI], 1.20-3.11; P = .0065; and 69.6% vs. 48.1%; OR, 2.48; 95% CI, 1.40-4.40; P = .002, respectively). The median OS improved from 22.8 months for patients in period 1 to 38.2 months for patients in period 2 (univariate analysis: hazard ratio, 0.65; 95% CI, 0.50-0.83; P = .001). Conclusion Patients who started treatment during the past 5 years were exposed to a greater number of treatment lines compared with patients treated before 2011. Our data suggest that the increase of treatment options available and clinician expertise could be associated with better outcomes.