In this retrospective analysis, we explored the prognostic and predictive value of the systemic immune-inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, at baseline and ...changes at week 6 during first-line sunitinib in patients with metastatic renal cell cancer (RCC).
Patients were stratified into high SII (≥ 730) and low SII (< 730) groups. SII was associated with objective response, p < 0.0001. The median PFS was 6.3 months (95% CI 5.5-8.9) in patients with SII ≥ 730 and 18.7 months (95% CI 14.7-22.8) in those with SII < 730, p < 0.0001. The median OS was 43.6 months (95% CI 35.3-52.1) in patients with SII < 730, and 13.5 months (95% CI 9.8-18.5) in those with SII ≥ 730, p < 0.0001. In multivariate analysis, performance status, IMDC score and SII were able to predict OS (HR = 3.29, HR = 1.71 and HR = 1.79, respectively).
We included 335 consecutive RCC patients treated with first-line sunitinib. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion at week 6 of treatment on PFS and OS was evaluated by Cox regression analyses.
The SII and its changes during treatment represent a powerful prognostic indicator of clinical outcome in patients with metastatic RCC.
Renal cell carcinoma (RCC) constitutes approximately 3% of all cancers. More than 60% of RCCs are detected incidentally; one-third of patients present with regional or distant metastases, and another ...20-40% of patients develop metastases after radical nephrectomy. RCC can metastasize to any organ. In contrast, metastatic RCC (mRCC) without evidence of a primary tumor is extremely rare, with only a few reported cases.
We present a case of mRCC that initially presented with multiple liver and lymph node metastases but no primary renal lesion. An impressive response to treatment was achieved with a combination of immune checkpoint inhibitors and tyrosine kinase inhibitors. A clinical, radiological, and pathological diagnostic strategy, particularly in the context of a multidisciplinary team, are crucial for reaching a definitive diagnosis. This approach allows to select the appropriate treatment, making a huge difference for a mRCC due to its resistance to standard chemotherapy.
There are currently no guidelines available for mRCC without primary tumor. Nevertheless, a combination of TKI and immunotherapy could be the optimal first-line treatment if systemic therapy is required.
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•Different immune checkpoint inhibitors are approved for urological tumors.•Little is known about the treatment after progression or toxicity on immunotherapy.•Retreatment with an ...immune checkpoint inhibitor could be feasible in some cases.
Immune checkpoint inhibitors (ICIs) have led to a significant change in the treatment of urological tumors where several agents are currently approved. Yet, most patients discontinue treatment due to disease progression or after the onset of severe immune-related adverse events (IRAEs). Following promising results in melanoma patients, retreatment with an ICI is receiving increasing attention as an attractive option for selected patients.
We performed a literature review focusing on the feasibility, safety, timing and activity of ICI rechallenge in genitourinary cancers where very little information is available. We classified the different ICI retreatment strategies into three main clinical scenarios: retreatment after terminating a prior course of ICI while still on response; retreatment after interruption due to IRAEs; retreatment after progression while on ICI therapy.
The pros and cons of these options in the field of urological tumors are then discussed, and critical suggestions proffered for the design of future clinical trials.
Urothelial carcinoma (UC) is a common malignancy with a high mortality rate when metastatic. Traditionally, systemic therapy consisted in platinum-based regimens as first-line, with Taxanes or ...Vinflunine as further lines. Recently, checkpoint inhibitors (CPIs) immunotherapy has emerged as a new therapeutic option.
We searched in Medline, Pubmed and ClinicalTrial.gov databases for the relevant literature, reviewing the results of published trials and the design of ongoing studies involving CPIs in UC.
Strong evidence supports the use of CPIs after failure of Cisplatin-based chemotherapy, although no predictive parameter is available so far. Expression of Programmed-Death-1-Ligand has given conflicting results, and is currently indicated only for the selection of Cisplatin-ineligible patients who should receive CPIs.
The therapeutic landscape of UC is rapidly changing due to the availability of CPIs. Neoadjuvant trials with CPIs and trials combining two CPIs are promising and will further expand the use of immunotherapy.
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66
Background: MPI is an effective tool for geriatric assessment in elderly patients (pts). An oncological version of MPI (Onco-MPI) has been validated by our group in pts with cancer. ...We evaluate here the prognostic role of Onco-MPI in pts affected by urological cancer. Methods: Pts aged ≥70 years with prostate, renal and urothelial cancer (bladder or upper urinary tract) referred to the Medical Oncology 1 Unit from Jan 2005 to Aug 2019 received a basal comprehensive geriatric assessment (CGA). Onco-MPI was calculated by a validated algorithm as a weighted linear combination of the CGA domains as previously described, identifying 3 different prognostic groups: low (scores 0.0-0.46), intermediate (scores 0.47-0.63) and high risk (scores 0.64-1.0). Results: A total of 643 pts were included; 382 with prostate, 121 renal and 140 urothelial cancer. Median age was 77 years (68-95). ECOG PS was 0 in 44%, 1 in 34.2% and >1 in 21.6%; 19.3% had stage I or II disease, 29.7% stage III and 51% stage IV. Median overall survival (OS) was 35.4 months (95% CI 29.5-41.2). Onco-MPI score (low vs medium vs high risk) was significantly associated with OS in the overall population as well as in the subgroups of patients with prostate, renal or urothelial cancer (table). In pts with prostate cancer the majority of pts were low risk (93%) and only few intermediate (7%), no one was high risk. Conclusions: Onco-MPI confirmed its prognostic role in elderly pts with prostate, renal and urothelial carcinoma. It may be therefore valuable both in clinical practice for driving decision-making, and in geriatric clinical trials thanks to its standardization.Table: see text
558
Background: A multicenter CUP provided early access to avelumab 1LM in Italian patients (pts) with Ia/mUC before reimbursement. Real-world pt characteristics and outcomes with avelumab 1LM from ...READY were reported previously. Here, we report updated data and subgroup analyses of effectiveness with avelumab 1LM. Methods: This prospective, noninterventional CUP included pts with la/mUC who were progression free after 1L platinum-based chemotherapy (PBC; 4-6 cycles, starting avelumab 1LM 4-10 wk after last PBC dose). Pts were enrolled from Jan 18, 2021 to Mar 7, 2022. Avelumab was provided per physician request and after approval by local ethics committees, per Italian compassionate-use regulations. Pts who had a relapse within 12 mo of prior adjuvant or neoadjuvant systemic therapy, including immune checkpoint inhibitors, were excluded. Results: 464 pts were included (78.45/21.55% male/female; median age, 70.0 y interquartile range, 63.0-76.0). At data cutoff (July 30, 2023), median follow-up from start of avelumab 1LM in 411 evaluable pts was 20.24 mo (95% CI, 19.78-20.93); median overall survival (OS) and progression-free survival (PFS) from start of avelumab were 26.22 mo (95% CI, 19.97-not estimable NE) and 7.63 mo (95% CI, 5.79-9.24), respectively. In pts aged <60 y (n=53), 60-70 y (n=150), and >70 y (n=208), median OS (95% CI) was not reached (NR; 12.86 mo-NE), NR (24.21 mo-NE), and 24.01 mo (16.94-NE), and median PFS was 5.20 mo (2.83-6.71), 7.70 mo (5.26-10.07), and 8.82 mo (6.05-12.93), respectively. In pts who received 1L cisplatin + gemcitabine (n=183) and 1L carboplatin + gemcitabine (n=219), median OS (95% CI) was NR (16.05 mo-NE) and 25.10 mo (19.97-NE), and median PFS was 6.61 mo (5.30-9.18) and 8.42 mo (6.05-12.73), respectively. The table shows OS and PFS in other subgroups defined by best response to 1L PBC and number of 1L PBC cycles received. Conclusions: Real-world outcomes with avelumab 1LM in this CUP in Italy show clinical benefit across various subgroups. These data are clinically relevant and are consistent with other real-world country-based studies and the phase 3 JAVELIN Bladder 100 trial. Findings further support the use of avelumab 1LM as standard of care in pts with la/mUC who are progression free after PBC. Table: see text
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Background: ECHOS trial is a large real-world study which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, > 1500 pts were included in the ...study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the outcomes of pts ≥75 yrs old who received DOC for mCSPC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. Results: Among 920 mCSPC pts treated with DOC, 132 (14.4%) were ≥ 75 yrs old. Most of them (76%) presented de novo disease with high-volume features. Their baseline characteristics were similar to those of younger pts excepting for baseline hemoglobin levels which were significantly lower in older pts (median 12.6 vs 13.5; p = 0.001). Older pts received either a reduced dose (16.7%) or a modified schedule (8.4%) more frequently than younger one (p < 0.0001). Thirty-six pts experienced a grade 3-4 toxicity, which was mainly hematological (75% of the cases). The median progression-free survival (PFS) was 12.6 mos in older pts compared to 14.9 mos observed in younger ones (p 0.2). The median number of life prolonging agents administered after DOC progression was 1 in pts ≥75 yrs as well as in pts < 75 yrs. The median overall survival (OS) was 27.9 mos and 42.4 mos in older and younger pts, respectively (p < 0.0001). Conclusions: Our data suggest that DOC was efficacious and well-tolerated in mCSPC pts ≥75 yrs although the treatment was administered with either dose or schedule modifications in about 25% of the cases. No differences were observed in terms of PFS between pts ≥75 and ones < 75 yrs. Nevertheless, the median OS of older pts was significantly worse compared to that of younger ones.
Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour, which can arise at any site. There is little published data about the management of these tumours.
A retrospective review of ...patients with histologically-proven EHE presenting to the Royal Marsden Hospital from January 1999 to January 2012.
Thirty-two patients (23 females) were identified with a median age of 44 (range=17-78). Twenty patients presented with diffuse disease. Median overall survival (OS) was 9.8 years in 10 patients with operable disease. Amongst those with inoperable disease (n=22), patients with liver disease had the longest median OS (9.8 years), while those with lung and mediastinal disease had the shortest OS (3.6 years). A variety of treatments were used for inoperable disease with infrequent radiological responses.
The clinical behaviour can vary depending on the site of disease. Surgery, if feasible, has the best outcome. In those with inoperable disease, a period of observation to assess the tumour behaviour is recommended. The role of medical therapy remains unclear.
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Background: Nivolumab, an immune checkpoint inhibitor of PD-1, demonstrated a significant OS benefit in patients with metastatic renal cell carcinoma (mRCC), in progression after a previous line ...of therapy with anti-VEGFR agents. However, the features of effective immune response and predictive biomarkers of clinical benefit to PD-1 blockade have not yet been recognized. Methods: I-RENE is a prospective translational multicenter Italian study of a real-life mRCC patients treated with nivolumab or cabozantinib after failure of therapy with anti-VEGFR agents. 82 patients were enrolled from December 2018 to August 2022 (nivo 60, cabo 22), with blood samples obtained at baseline and at different time points in both treatment groups. An extended concept of "immune liquid biopsy" is being applied to the study, consisting in the phenotypic and transcriptional profile of lymphoid and myeloid subsets, immune-related miRNA quantification, cyto/chemo-kinome and RNAseq of extracellular vesicle. Results: Multiparametric flow cytometry, performed to monitor the blood frequency and different myeloid and lymphoid cells, show that monocyte subsets (classical, intermediate and non-classical CD14
+
cells), monocytic myeloid derived suppressor cells (MDSC, such as CD14
+
HLA-DR
neg
and CD14
+
PD-L1
+
) and polymorphonucleate (PMN)-MDSC, remain either stable or increase during treatment; concomitantly, CD8
+
PD-1
+
T cells (detected by anti-nivolumab IgG4) increment frequency, acquire the effector CD45RA
-
CCR7
+
phenotype and express the proliferating marker Ki67. Patients receiving cabozantinib display instead a remarkable decrease of all myeloid cell subsets, paired by the boost of cytotoxic CD3
-
CD16
+
CD56
dim
NK cells and more marginally of CD8+PD1+ cells, Preliminary correlations indicate that clinical benefit of nivolumab seems to cluster with the lack of CD14+ cells and M-MDSC increase and blood frequency of total, and the boost in CD8
+
CD45RA
-
CCR7
+
Ki67
+
effector T cells. In contrast, the cabozantinib-induced immune modulation occurring in patients treated with does not associate with clinical response Conclusions: This first set of data indicate blood as promising source of dynamic biomarkers for the development of algorithms predicting response to PD-1 blockade. Furthermore, the results so far collected suggest that the potent immunomodulation induced by cabozantinib on the immunosuppressive myeloid compartment may not lead to any tumor control in the absence of specific immune stimulation by checkpoint inhibitors. This study was supported by the Italian Ministry of health (RF-2016_02363001). Clinical trials.gov: NCT04891055 Clinical trial information: NCT04891055 .
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Background: Peritoneal metastases (PM) have been reported in approximately 1% of patients (pts) with metastatic Renal Cell Carcinoma (mRCC). Outcome data are limited due to the rarity of this ...metastatic site. Therefore, the aim of our study is to describe RCC pts with PM treated as per clinical practice. Methods: Baseline characteristics and outcome data of pts with PM from RCC were retrospectively collected from 12 Italian oncological referral centers adhering to the Meet-Uro group, from January 2016 to September 2022. Results: We collect 91 RCC pts with PM. 87/91 pts received systemic treatment, 4/87 only best supportive care. First line treatment included TKI and ImmuneOncology(IO)-TKI with different Objective Response Rate(ORR) (41% vs 53.8%, respectively) and Disease Control Rate (DCR) (57.1% and 80.7%, respectively) as well as median PFS (9.9 mo (95%CI 4.5-15.4) for TKI and not reached (NR) for IO-TKI (69.7% pts were free from progression at a median follow up of 13.8 months). Primary refractory (PR) pts were 35.7% for TKI and 7.7% for IO-TKI. According to IMDC score, mPFS was consistent among risk categories, 36.8 mo (95%CI 9.6-63.9) for good risk pts, 13.8 mo (95%CI 8.8-18.8) for intermediate pts and 2.9 mo (95%CI 2.2-3.7) for poor risk pts. Synchronous PM was associated to shorter mPFS 11.0 (95%CI 3.1-19.0) compared to patients with metacronous involvement as well as ORR (31.3%) and DCR (43.1%) whereas PR was higher (34.7%). Only 43/87 pts (45.7%) received a second line treatment that was TKI ( ORR 30.7%; DCR 61.5%; or IO (ORR 20.6%; DCR 41.3%). mOS was 21.8 mo (12.0-31.5) for TKI and NR for pts treated with IO-TKI (80.8 alive at 1 yrs). According to IMDC score, mOS was NR for good risk pts, 24.6 (95%CI 15.8-33.3) and 3.4 (95%CI 2.4-4.3) for intermediate and poor risk, respectively. Conclusions: We report one of the largest case series regarding PM from RCC. Poor risk patients according to IMDC score, sarcomatoid feature and liver metastasis were more represented in our population, compared to historical control, suggesting a more aggressive behavior of PM mRCC. Outcome data suggest that TKI-IO as first line treatment, compared to TKI monotherapy, and TKI as second line, compared to IO, are more active treatment for these pts with dismal prognosis. Nevertheless, synchronous PM has been reported in 57% of pts with poorer outcome and lower response rate. Table: see text
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