681 Background: The therapeutic landscape of metastatic Urothelial Carcinoma (mUC) is rapidly evolving, alongside increasing opportunities to analyze molecular alteration and molecular classification. FGFR alteration (FGFRa) occur in about 15-20% of mUC patients. Data from randomized-controlled THOR trial demonstrated the clinical efficacy of erdafitinib, an FGFR 1-4inhibitor, in pretreated FGFR3/2a mUC. So, real-world data (RWD) on FGFRa patients remain an unmet need. Methods: SATURNO (NCT06235268) is an Italian, multicenter, prospective, non-interventional study enrolling all mUC patients managed at the participant institutions from Nov 2023 to Sept 2025. The Web National Registry includes patients with metastatic disease or with nodal involvement not suitable to surgery. Participating institutions were selected to adequately represent different geographical area. Results: A total of 237 patients were tested for FGFRa. Among them, 171 (72%) were FGFR3/2a and 66 (28%) were FGFR wild-type (WT). In the FGFR3/2a group, 134/171 (78%) were male and 37/171 (22%) were female; 165/171 (96%) had pure urothelial carcinoma histology. The most common metastatic sites were lung (61/171, 35%), liver (21/171, 12%), bone (41/171, 24%), and retroperitoneal lymph nodes (50/171, 29%). Compared with FGFR WT patients, older age was significantly associated with FGFR3/2a (OR 1.05, 95% CI 1.02–1.09, p = 0.003). Retroperitoneal lymph node involvement was less frequent among FGFR3/2a patients (29% vs 44%, OR 0.53, 95% CI 0.29–0.95, p = 0.033). FGFR3/2a tended to be more common in upper tract urothelial carcinomas (UTUC) compared with bladder tumors (23.4% vs 12.1%, OR 2.12, 95% CI 0.98–5.15, p = 0.073). FGFR3/2a patients were less likely to receive maintenance therapy (OR 0.36, 95% CI 0.19–0.65, p < 0.001). Among patients treated with platinum-based combinations (91/171, 53%), 41/91 (45%) FGFR3a patients received avelumab maintenance compared to 31/58 (53%) in the FGFR WT subgroup. Additionally, 26/91 (29%) FGFR3a patients had primary refractory disease to platinum-based therapy, compared with 14/58 (24%) among FGFR WT patients. Conclusions: RWD from this prospective registry show that FGFR3/2a is more common in older patients and, consistent with previous reports, tends to occur more frequently in UTUC. Retroperitoneal nodal involvement, usually associated with better prognosis, is less common in FGFR3/2a. FGFR3/2a are less likely to receive avelumab maintenance therapy due to primary progression to platinum-based combination. Acknowledgments: The IT infrastructure on which the urothelial tumor registry is based was developed thanks to the unconditional support of Gilead Sciences. Clinical trial information: NCT06235268 .

586 Background: Immune checkpoint blockade is a standard-of-care treatment for mRCC patients, but the immune mechanisms driving clinical benefit remain underexplored. In the I-RENE trial (NCT04891055), we conducted a comprehensive evaluation of myeloid-derived suppressor cell (MDSC) and lymphoid dynamics and their impact on the efficacy of nivolumab. Methods: The I-RENE study is a prospective, translational, real-world multicenter trial involving mRCC patients treated with nivolumab after failure of previous VEGFR-targeted therapies. Sixty patients were enrolled between December 2018 and August 2022. Peripheral blood (PB) samples were collected at baseline and at 2, 4, and 12 weeks, as well as at disease progression. PBMCs were analyzed by high-resolution flow cytometry (profiling 144 lymphoid and myeloid cell subsets), and plasma was assessed using multiplex analysis (69 soluble factors). CD14+ monocytes from PB and tumor tissue were subjected to RNA sequencing. Results: Significant immune modulations in PB were detectable as early as 2 weeks into treatment across all patients, regardless of clinical response, and persisted throughout the 3-month observation period. These changes included substantial alterations in the profiles of immune cells and plasma soluble factors. Responders to nivolumab exhibited a marked reduction in monocyte subsets associated with immune suppression, such as CD14+HLA-DR- cells, CD14+PD-L1+ cells, and intermediate monocytes. In contrast, non-responders showed a progressive increase in suppressive monocytes and a concomitant decrease in CD14+ cells involved in anti-tumor immunity, including non-classical monocytes and CD14+ cells expressing HLA-DR and CX3CR1. Lymphoid compartment analysis revealed that responders experienced an increase in CD8+ T cells and CD4+ effector memory T cells, along with a reduction in CD38+ T cells. Conversely, non-responders showed significant upregulation of senescent CD8+ T cells (KLRG1+CD28-CD57+) and CD38+ T cells. All progressing patients showed a notable resurgence of suppressive myeloid cells (HLA-DR-, PD-L1+), confirmed by an enriched MDSC gene signature, as well as an increase in PB CD38+ and senescent T cells. Notably, the detrimental role of myeloid-driven immune suppression in non-responders was further confirmed by an enriched MDSC gene signature in matched tumor samples. Conclusions: The pervasive and detrimental impact of myeloid cells committed to immune suppression is evident even before radiological progression in mRCC patients and persists despite immunotherapy. These findings highlight the need for early identification of immune-suppressive infiltrates and the development of strategies to overcome or reprogram these cells, both at the systemic and tumor level, following diagnosis.

Background: Up to 30% of patients with metastatic castration-resistant prostate cancer (mCRPC) develop visceral metastases, which are associated with a poor prognosis. Objectives: Efficacy of enzalutamide in mCRPC patients with measurable metastases, including visceral and/or extra-regional lymph nodes. Methods: In this phase II multicenter study, patients with mCRPC and measurable metastases received enzalutamide as the first line. Primary endpoint: 3-month (mo) disease control rate (DCR) defined as the proportion of patients with complete (CR) or partial response (PR) or stable disease (SD) as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoint: safety. Exploratory endpoint: the association between ARv7 splicing variants in basal circulating tumor cell (CTC)-enriched blood samples and treatment response/resistance using the AdnaTest ProstateCancerSelect kit and the AdnaTest ProstateCancer Panel AR-V7. Results: From March 2017 to January 2021, 68 patients were enrolled. One patient never started treatment. Median age: 72 years. A total of 52 patients (78%) received enzalutamide as a first line for mCRPC. The median follow-up was 32 months. At the 3-month assessment, 24 patients presented an SD, 1 patient achieved a CR, and 23 patients had a PR (3-mo-DCR of 72%). Discontinuations due to adverse events (AEs), disease-related death, or disease progression occurred in 9%, 6%, and 48% of patients. All patients reported at least one grade (G) 1–2 AE: the most common were fatigue (49%) and hypertension (33%). Six G3 AEs were reported: two hypertension, one seizure, one fatigue, one diarrhea, and one headache. Basal detection of ARv7 was significantly associated with poor treatment response (p = 0.034) and a nonsignificant association (p = 0.15) was observed between ARv7 detection and response assessments. At month 3, ARv7 was detected in 57%, 25%, and 15% of patients undergoing progressive disease, SD, and PR, respectively. Conclusion: The study met its primary endpoint, showing the efficacy of enzalutamide in men with mCRPC and measurable metastatic lesions in visceral and/or lymph node sites. Trial registration: ClinicalTrials.gov Identifier: NCT03103724. First Posted: 6 April 2017. First patient enrollment: 19 April 2017.

Background: The preferred 1L Rx for pts with mccRCC is either ipi+nivo or PDi + TKI (NCCN Guidelines V4.2023).Cabo was approved based on Ph3 METEOR trial results from pts after prior mccRCC progression on 1-2 TKIs but not PDi Rx.In real world, cabo is the most used 2L therapy but its effectiveness after prior PDi based combination is unknown.Methods: De-identified nationwide (US based) Flatiron Health EHR-derived database was used.Inclusion: diagnosis of mccRCC, 1L Rx with ipi+nivo or PDi+TKI (from 10/ 2017 to 7/2022) followed by 2L Rx with single-agent cabo.Exclusion: 1L Rx with cabo, pts with no documentation of 1L Rx or pts with no evidence of contact for 90 days from diagnosis of mccRCC at treating institution to ensure pts were actively engaged in care at the data providing institution.TTNT (time to next therapy; measured from 2L to 3L) and overall survival (OS; measured from 2L) were summarized via Kaplan-Meier survival estimates with 95% confidence interval (CI) and compared in the context of propensity score (PS) matching weighted analysis and Cox proportional hazard model (PSM-CoxHzM).PS model included baseline covariates: age, race, smoking status, practice type, insurance, year of 1L, IMDC risk factors (all six), and missingness of covariates.Missing data were multiply imputed using predictive mean matching on 50 chained equations.All analysis done using R version 4.2.3.Results: Of 12,285 mccRCC pts in the dataset, 237 pts met eligibility, and all received ipi+nivo or PDi+TKI followed by cabo.Results summarized in table.Table: 1899P Median TTNT (95% CI) mos Median OS (95% CI) mos Ipi+nivo (n¼145) 8.0 (6.9 -11) 26 (21 -32) PDi+TKI (n¼92) 7.5 (6.3 -16) 34 (27-NR) PSM-CoxHzM Hazard ratio (95% CI, p-value) 1.43 (0.98 -2.11, 0.07) 1.16 (0.73 -1.83, 0.88) Conclusions: Cabo retained similar effectiveness in 2L regardless of prior ipi+nivo or PDi+TKI.These results may aid with counseling of pts, prognostication, treatment decision in clinic and design of future clinical trials.

712 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 .

We aimed to overcome intratumoral heterogeneity in clear cell renal cell carcinoma (clearRCC). One hundred cases of clearRCC were sampled. First, usual standard sampling was applied (1 block/cm of tumor); second, the whole tumor was sampled, and 0.6 mm cores were taken from each block to construct a tissue microarray; third, the residual tissue, mapped by taking pieces 0.5 × 0.5 cm, reconstructed the entire tumor mass. Precisely, six randomly derived pieces of tissues were placed in each cassette, with the number of cassettes being based on the diameter of the tumor (called multisite 3D fusion). Angiogenic and immune markers were tested. Routine 5231 tissue blocks were obtained. Multisite 3D fusion sections showed pattern A, homogeneous high vascular density (10%), pattern B, homogeneous low vascular density (8%) and pattern C, heterogeneous angiogenic signatures (82%). PD-L1 expression was seen as diffuse (7%), low (33%) and absent (60%). Tumor-infiltrating CD8 scored high in 25% (pattern hot), low in 65% (pattern weak) and zero in 10% of cases (pattern desert). Grading was upgraded in 26% of cases (G3–G4), necrosis and sarcomatoid/rhabdoid characters were observed in, respectively, 11 and 7% of cases after 3D fusion (p = 0.03). CD8 and PD-L1 immune expressions were higher in the undifferentiated G4/rhabdoid/sarcomatoid clearRCC subtypes (p = 0.03). Again, 22% of cases were set to intermediate to high risk of clinical recurrence due to new morphological findings of all aggressive G4, sarcomatoid/rhabdoid features by using 3D fusion compared to standard methods (p = 0.04). In conclusion, we propose an easy-to-apply multisite 3D fusion sampling that negates bias due to tumor heterogeneity.

During COVID pandemic, many cancer patients (pts) refused to come to hospital, suspending therapies, with ominous consequences. Based on positive (+) results of DOMONCOVID, our homecare project for COVID+ cancer pts, we created a new model of assistance, ONCOHOME, delivering cancer care at home to immune-compromised pts. We aim to provide data on feasibility, efficacy and costs of this innovative model.

Background: Cancer represents a major risk factor for COVID-19 poor outcomes. During the crucial phase of the pandemic, we launched a home care project, called DomOnCOVID, aiming to provide care to patients in their own homes, enabling to keep immunocompromised individuals away from health care facilities, decrease hospital use, and strengthen hospital capacity for subjects with COVID-19 and other conditions. This paper describes this intervention in terms of feasibility and clinical outcomes. Methods: This is a descriptive study of cancer patients with confirmed or suspected COVID-19 infection assisted at home in the Italian Province of Cremona during the pandemic’s first peak. We devised an organizational home care system which included a medical and nursing team equipped with a car for home visits, and a nurse manager who screened patient calls requesting inclusion in the project. The team administered oral drugs at home (chemotherapy, TKis, etc.) and was equipped with all necessary tools to conduct examinations, check vital signs, take blood samples, and nasopharyngeal swabs for COVID-19 testing. Results: From March 23rd to May 15th 2020, 71 cancer patients were assisted at home (181 visits, mean 2.5, SD 1.6 range 1-7). All had symptoms that could be traced back to COVID infection, but only 26/71 (37%) were found to be COVID+; 19/26 (73%) had mild symptoms, while 7 with severe symptoms were hospitalized and 2 died for COVID-19. The remaining patients recovered. 43/71 (60%) received at home oral or subcutaneous drugs and no particular problems or toxicity were observed. 16/28 (57%) of individuals living with COVID+ patients were found to be COVID+, while none of the non-cohabiting were COVID+. Conclusion: Delivery of cancer care at home is feasible and may be particularly useful not only during health crises but also after the epidemic in order to reduce hospital access, patient and care-giver travel and improve their quality of life. Further implementation studies on home-based care in oncology are warranted.

5052 Background: Enzalutamide is a second-generation androgen receptor inhibitor that showed to prolong survival in different setting of prostate cancer. Visceral metastases, occurring in 10–30% of mCRPC pts, have been associated with poor outcomes. Given the poor prognosis, trial investigating hormone therapies often excluded men with visceral disease, especially in the pre-docetaxel setting. To date, there are no prospective studies designed ad hoc to test hormone therapies in this subgroup of pts. Methods: In this open label phase II multicentre study mCRPC pts with visceral metastases were treated with enzalutamide 160 mg orally once daily as first or second line after docetaxel until progressive disease or unacceptable toxicity. Pts were eligible if they had documented measurable metastatic visceral disease (according to RECIST 1.1 criteria), including lesions in lung or liver or extraregional lymphnodes. Pts must have PSA progression or radiographic progression (according to PCWG2). Primary endpoint was to determine the clinical benefit, as measured by 3-months (mo) disease control rate (DCR) defined as the proportion of pts with best overall response of confirmed complete (CR) or partial responses (PR) or stable disease as per RECIST 1.1 at mo 3. Secondary endpoints were safety, quality of life (assessed by EQ-5D-5L e FACT-P questionnaire), pain assessment (by BPI-SF questionnaire). Exploratory objectives were to assess the association between ARv7 splicing variants (in CTCs samples) and treatment response/resistance. For CTC and ARv7 detection, we used the Adna test Prostate Cancer Panel. Results: From March 2017 through January 2021, 68 pts were enrolled at 6 Italian centres. One pt never started treatment because of withdrawal of consent. Median age was 70 years (IQR 65- 78). All pts presented with visceral disease at baseline: 27, 6, 55 pts presented with lung, liver and lymphnodes lesions, respectively. 26 pts presented with only one metastatic site, 22 pts with two, while the remaining part with multiple sites. 15 pts received a previous treatment with docetaxel in the mCRPC phase. The median follow-up was 10 mo. The median time on treatment was 8 mo. At mo 3, 24 pts presented a stable disease, 1 pt achieved a confirmed CR and 20 pts a PR for a 3 mo-DCR of 67% (45/67). Discontinuations due to adverse-events, disease-related death, or disease progression occurred in 6%, 7%, and 40% of pts, respectively. So far, only 26 patients were evaluated for baseline CTC and ARv7. Interestingly, 75% of patients experiencing a progression at month 3 were classified as ARv7 positive at baseline. Conclusions: The study met its primary endpoint showing enzalutamide is an active treatment option for men with mCRPC and visceral disease in both pre or post-docetaxel setting. CTCs status combined with ARv7 detection could be useful to personalize treatments. Clinical trial information: NCT03103724.

Abstract Background: HER2 mutations are oncogenic in hormone receptor positive (HR+) metastatic breast cancer (MBC), and may confer resistance to prior endocrine therapy but retain sensitivity to neratinib. Neratinib is an oral, irreversible, pan-HER tyrosine kinase inhibitor with clinical activity either as a single agent or in combination with fulvestrant in HER2-mutated, HER2-non-amplified MBC. Genomic analyses suggest that acquired resistance to neratinib can occur via additional HER2 alterations, which may alter HER2-pathway signaling. We investigated whether dual HER2-targeted therapy could improve clinical benefit in a cohort of patients with HER2-mutant, HR+ MBC treated with neratinib + trastuzumab + fulvestrant (N+T+F) from SUMMIT - a phase 2 basket trial (NCT01953926). Methods: Patients with HR+ MBC with known or suspected pathogenic HER2 mutation(s) identified by genomic sequencing were eligible to receive N+T+F (oral neratinib 240 mg/day, i.v. trastuzumab 8 mg/kg initially followed by 6 mg/kg every 3 weeks, and i.m. fulvestrant 500 mg on days 1&15 of month 1, then on day 1 every 4 weeks). Loperamide prophylaxis was mandatory during the first 2 treatment cycles. There was no restriction on the number of prior lines of systemic treatment for MBC. Efficacy endpoints: confirmed objective response rate and clinical benefit rate (RECIST v1.1); duration of response; progression-free survival. Results: As of 22-May-2020, 46 patients were enrolled in the N+T+F cohort and received at least 1 dose of study medication (safety population). 14 unique HER2 allelic variants were identified: 8 kinase domain missense; 1 extracellular domain missense; 2 transmembrane domain missense; 2 exon-20 insertion; 1 exon-19 deletion. The most common HER2 mutant variant was L755S (n=15, 33%) Median number of prior systemic regimens for metastatic disease was 4 (range 0-10); 34 (74%) patients had received prior fulvestrant, and 31 (67%) patients had received prior cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy. 16 (35%) patients had ductal histology, 29 (63%) had lobular carcinoma, and 1 (2%) had mixed ductal and lobular carcinoma. At this time, 30/46 patients had RECIST measurable disease and are efficacy evaluable (ongoing patients who did not have the opportunity for their first post-baseline tumor assessment were excluded); clinical activity - see Table. Diarrhea was the most commonly reported adverse event (80% any grade) with 15 (33%) patients reporting grade 3 diarrhea (no grade 4 diarrhea). 10 patients (22%) had a neratinib dose reduction due to diarrhea but no patients discontinued treatment due to diarrhea. Conclusions: The combination of N+T+F demonstrated encouraging clinical activity in heavily pre-treated HER2-mutant, HR+, HER2-non-amplified MBC, including patients who had previously received either fulvestrant and/or CDK4/6 inhibitor-based therapies. While the rate of grade 3 diarrhea was higher than that observed with single-agent neratinib in SUMMIT, this was manageable through loperamide prophylaxis, and no patients discontinued study treatment due to diarrhea. SUMMIT has recently been amended to evaluate N+T+F, T+F and F (1:1:1 randomization) and continues to enroll patients. RECIST measurable and efficacy evaluable patients (n=30)Confirmed objective response,a n (%)12 (40)CR0PR12ORR, % (95% CI)40 (23-59)Best overall response, n (%)18 (60)CR0PR18Best overall response rate, % (95% CI)60 (41-77)Medianb DOR, months (95% CI)8.4 (4.1-NE)Clinical benefit,c n (%)14 (47)CR or PR12SD ≥24 weeks2CBR, % (95% CI)47 (28-66)Medianb PFS, months (95% CI)8.3 (4.2-12.5)aORR is defined as either a CR or a PR that is confirmed no less than 4 weeks after the criteria for response are initially met; bKaplan-Meier analysis; cCBR is defined as confirmed CR or PR or SD for ≥24 weeks; CR, complete response; CBR, clinical benefit rate; DOR, duration of response; NE, not estimable; ORR, objective response rate; PFS, progression-free survival; PR, partial response; SD, stable disease. Citation Format: Komal Jhaveri, Cristina Saura, Angel Guerrero-Zotano, Iben Spanggaard, François-Clement Bidard, Jonathan W Goldman, José A García-Sáenz, Andrés Cervantes, Valentina Boni, John Crown, Adam Brufsky, Sherene Loi, Barbara Haley, Ingrid A Mayer, Stephen Chia, Janice Lu, James Waisman, Noa Efrat Ben-Baruch, Mark E Burkard, Jennifer M Suga, Lucía González-Cortijo, Bruno Perrucci, Feng Xu, Sofia Wong, Jie Zhang, Lisa D Eli, Alshad S Lalani, Hans Wildiers. Latest findings from the breast cancer cohort in SUMMIT - a phase 2 ‘basket’ trial of neratinib + trastuzumab + fulvestrant for HER2-mutant, hormone receptor-positive, metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD1-05.

Background: The province of Cremona had one of the highest incidence of COVID-19 (COV-19) infection in Italy The pandemic determined a significant shrinkage of our healthcare resources with difficulty for many patients (pts) to be assisted in the hospital, especially for the risk of being infected Therefore, we created a homecare project for cancer pts with the aim of reducing hospitalizations, accesses to the oncology ward and emergency room Methods: The team was composed by oncologists and nurses from the Oncology Unit of Cremona Community Hospital, supported by a secretary with a dedicated telephone number The assistance was provided from Monday to Saturday, 9 AM-5 PM Cancer pts were eligible if presenting confirmed diagnosis or suggestive symptoms for COV-19 A telephonic triage was performed Cancer pts and their cohabitants were tested with at least 2 nasopharyngeal swabs (NPS) Blood test, medical examinations and vital parameters were performed We advised screened individuals to follow the quarantine procedures, providing them with an information leaflet We administered oral/infusional treatments, including antiviral drugs Results: From March 23rd to April 30th 2020, 71 cancer pts were assisted at home, with a total of 191 visits Of the 71 pts tested with NPS, 26 resulted COV-19 positive (COV-19+) 19 of COV-19+ pts had mild symptoms;7 pts with stable vital parameters and initial pneumonia were successfully treated at home with hydroxychloroquine, antivirals and NSAIDs 7 pts with severe symptoms were promptly hospitalized 4 of them died, 2 due to the infection, 2 to progression disease 52 cohabitants were screened with NPS, 28 lived with a COV-19+ cancer patient;in this subgroup, 16 resulted COV-19+ 15 of them were completely asymptomatic Conclusions: This project demonstrated the feasibility of an innovative model based on homecare assistance for COV-19+ cancer pts with mild symptoms This strategy, limiting the number of hospital accesses for COV-19+ pts, might be useful to contain the spread of the infection Further studies are needed to test this strategy in COV-19 negative cancer pts Moreover, our experience indicates a high probability of identifying asymptomatic positive individuals cohabiting with COVID+ pts NPS screening for asymptomatic subjects is not routinely performed in Italy There is a urgent need to extend the screening to this population

The province of Cremona had one of the highest incidence of COVID-19 (COV-19). The pandemic determined a significant shrinkage of healthcare resources with difficulty for many patients (pts) to be assisted in the hospital, especially for the risk of being infected. We created a homecare project for cancer pts with the aim of reducing hospitalizations, accesses to the oncology ward and emergency room. The team was composed by oncologists and nurses from the Oncology Unit of Cremona Hospital, supported by a secretary with a dedicated phone number. The assistance was provided from Mon to Sat, 9 AM-5 PM. Cancer pts were eligible if presenting confirmed diagnosis or suggestive symptoms for COV-19. A telephonic triage was performed. Cancer pts and their cohabitants were tested with at least 2 nasopharyngeal swabs (NPS). Blood test, medical examinations and vital parameters were performed. We advised screened individuals to follow the quarantine procedures, providing them with an information leaflet. We administered oral/infusional treatments, including antiviral drugs. From March 23rd to April 30th 2020, 71 cancer pts were assisted at home, with a total of 191 visits. Of the 71 pts tested with NPS, 26 resulted COV-19 positive (COV-19+). 19 of COV-19+ pts had mild symptoms; 7 pts with stable vital parameters and initial pneumonia were successfully treated at home with hydroxychloroquine, antivirals and NSAIDs. 7 pts with severe symptoms were promptly hospitalized. 4 of them died, 2 due to the infection, 2 to progression disease. 52 cohabitants were screened, 28 lived with a COV-19+ cancer patient; in this subgroup, 16 resulted COV-19+.15 of them were asymptomatic. This project demonstrated the feasibility of an innovative model based on homecare assistance for COV-19+ cancer pts with mild symptoms. This strategy, limiting the number of hospital accesses for COV-19+ pts, might be useful to contain the spread of the infection. Further studies are needed to test this strategy in COV-19 negative cancer pts. Moreover, our experience indicates a high probability of identifying asymptomatic positive individuals. NPS screening for asymptomatic subjects is not routinely performed. There is a urgent need to extend the procedure to this population.

e16023 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active chemotherapy regimens in mUC. We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a single institution, explorative trial. The aim is to evaluate the incremental benefit of the two regimens in terms of complete response and long term survival. We treat all consecutive, chemo-naïve mUC patients with 4 cycles of CGP dose-dense every 14 days followed by 4 cycles of MVAC every 14 days. In all cycles we used Pegfilgrastim 6 mg on day 3. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: From 2007 to 2018, 67 consecutive pts were included. Male were 82%; median age 66 years (33-83); Bajorin risk factors was 0 in 31%, 1 in 52%, 2 in 16%. The majority of pts were hospitalized for three days during chemotherapy and received hydration and supportive therapy. After the first 4 cycles of CGP, we observed 7% CR, 46% PR, 31% SD, and 12% PD. After the 4 sequential cycles of MVAC DD we observed a global 25% of CR, 33% PR, 10% SD, and 24% PD. Median TTP was 8.2 months (95% CI, 7.3-10.1) and median OS was 18 months (95% CI, 10.8-26.1). 5 pts are still alive after more than 30 months and maintaining complete response. Main grade 3–4 toxicity included anemia 27%, asthenia 23%, neutropenia 19% (febrile 7%), thrombocytopenia 13%. Conclusions: The sequential use of these two DD regimens is active and leads to an increased number of complete response and possible longer survival. A randomized trial is needed to confirm our results.

The global growing number of contrast-enhanced procedures highlights the risk of contrast media–induced renal damage. This review is an effort to define contrast-induced nephropathy and its pathogenesis, weigh its principal risk factors, give some clarifications about kidney function evaluation tools, acquire some clinical relevance prognostic concerns, and bring into focus preventive measures, with special regard to cancer patients. Our final purpose is focused on the request of diagnostic safety in high-risk patients, which may be achieved without unfair differences in this subgroup, too. A second reading of the scientific evidence may offer a chance to tear down the kidney damage ghost, replacing it with the consciousness of a still existing challenge that engages more than one specialty.

Purpose To evaluate the efficacy and safety of dose-dense TCF in elderly (≥65 years) compared to younger patients. Methods Safety and efficacy data relative to 119 consecutive patients with locally advanced or metastatic gastric cancer treated at our institution and enrolled in different phase II trials were retrospectively collected. All patients were treatment-naive and received docetaxel 70 mg/m 2 day 1, cisplatin 60 mg/m 2 day 1, l-folinic acid 100 mg/m 2 days 1-2, followed by 5-fluorouracil 400 mg/m 2 bolus days 1-2, and then 600 mg/m 2 as a 22-hour continuous infusion days 1-2, every 14 days, plus pegfilgrastim 6 mg on day 3. Sixty patients (50%) aged ≥65 years received the same schedule with a dose reduction by 30%. Results A total of 86% of patients were evaluable for response and all for toxicity. In patients aged ≥65 years, we observed an overall response rate of 51%. Median overall survival was 11.2 (95% confidence interval [CI] 7.3-15.1) and 11.8 months (95% CI 9.2-16.2) in elderly and younger patients, respectively. In the elderly patients, the most frequent grade 3-4 toxicities were neutropenia (13%), leukopenia (7%), thrombocytopenia (18%), anemia (3%), and febrile neutropenia (8%); in the younger patients, neutropenia (56%), leucopenia (31%), thrombocytopenia (22%), anemia (15%), and febrile neutropenia (15%). Conclusions Elderly patients can be safely treated with a dose-dense TCF regimen with a 30% dose reduction achieving similar efficacy results as younger patients with lesser toxicity.

e16031 Background: To assess the clinical impact of VFL in pts with mTCCU and verify the prognostic factors in a large, unselected population treated according to routine clinical practice (CP). Methods: This is a retrospective, observational multicenter trial. According to the Italian Regulatory Agency Registry (AIFA), all oncological centers that treated with VFL at least 4 pts from Feb 2011 to June 2014, were invited to take part to this study. Pts must have received a previous platinum therapy and were treated with VFL according to CP. Primary objective is to test whether efficacy in terms of overall survival (OS) obtained in the registration study are confirmed in the real life setting. Sample size has been determined considering the OS obtained in the registration study, with α=0.05 and 1-β=80%, 197 pts have to be enrolled. Results: 217 pts were registered in 24 centers across all Italy. Median age was 69 yrs; 84% males; ECOG was 0,1,2 in 47%, 46%, and 7%; 21% had liver metastasis. 77% received VFL as second-line and 23% as third-line. The median number of VFL cycles was 4; 29% received an initial dose of 320 mg/m, 35% 280 mg/m and 36% a lower dose. Toxicity was manageable, 21% had a grade 3-4: neutropenia 9%, asthenia/fatigue 7%, leucopenia 2%, constipation 5%. Conclusions:The good efficacy of VFL was confirmed in this large unselected cohort treated according to routine CP. In our multivariate model ECOG PS, liver involvement and the number of involved organs were the main risk factors affecting OS. Hemoglobin level was not significant. No CR (%) PR (%) Median PFS (95% CI) Median OS (95% CI) Registration study 253 0 (0%) 16 (6%) 3.0 (2.1- 4.0) 6.9 (5.7- 8.0) Current study 217 6 (3%) 21 (10%) 3.2 (2.6- 3.7) 8.1 (6.3- 8.9) Univariate and multivariate analysis for overall survival No Median OS (95% CI) Log rank (p) HR (95% CI) p ECOG PS 0 101 9.7 (8.1-11.0) 15.3 (<0.001) 0.61 (0.45- 0.81) 0.001 N. of organs in volved =1 127 9.5 (8.0-10.6) 15.2 (<0.001) 0.66 (0.48- 0.89) 0.008 No liver involvement 171 8.6 (6.3-9.7) 11.2 (<0.001) 0.68 (0.47- 0.99) 0.045

e15552 Background: TCF is one of the most effective first-line option in metastatic GEC. We previously reported on the promising and high activity of mTCF-dd (Tomasello G et al: Gastric Cancer 2014 Oct;17(4):711-7). Aim of this study is to describe clinical outcomes, safety and studying potential clinical prognostic factors of this intensified regimen in a very large consecutive cohort of pts coming from a single center. Methods: 250 consecutive pts with measurable or evaluable GEC treated in the same institution were longitudinally followed. 136 were enrolled in 3 different CTs and 114 treated by routine clinical practice. Pts with PS 0-2 and adequate organ function from 2004 to 2015 received mTCF-dd: Docetaxel (50-85 mg/m2 d 1), Cisplatin (50-75 mg/m2 d 1), l-Folinic Acid (100 mg/m2 d 1-2), 5-FU (400 mg/m2 bolus d 1-2, and 600 mg/m2 as a 22 h c.i. d 1-2), plus Pegfilgrastim 6 mg d 3, q2w. Analysis was done accordint to ITT principle. Results: Median age 63 (range 25-81), M:F 140:51. Metastatic sites were: liver 38%, peritoneum 33.5%, bone 14%, lung 12%. A median of 4 cycles (range 1-8) per patient was administered: 15% required a dose reduction, 48% were treated without any delay. At a median follow up of 60 months, 192 pts were evaluable. We observed 6% CR, 52% PR, 14% SD, 13% PD and 13% NE, for an ORR of 59% (95% CI 52-66); DCR was 76%. Median OS was 11.1 months (95% CI 9.5-13.5). Most frequent grade 3/4 toxicities: neutropenia (26%), asthenia (31%), thrombocytopenia (17%), hypokalemia (16%), diarrhea (13%), febrile neutropenia (11%). 18 pts (9%) became operable after mTCF-dd and underwent surgery. Finally, we identified 18 pts (9%) [12 metastatic, 6 locally advanced] with OS > 3 years and 7 (4%) still maintaining a response at the time of the current analysis. A further group of 21 pts with bone mets at diagnosis bearing a very poor prognosis (OS: 7.8 m 95% CI 3.8-10 ) was also found. Overall population data and a multivariate Cox model will be presented at the meeting Conclusions: mTCF-dd in GEC is an effective and feasible option. A careful monitoring of adverse events is recommended. A biomolecular analysis of long-term survivors is underway.

Background: Following the results deriving from the RCT of VFL, this study aims to assess the generalizability of data in terms of overall survival in pts with metastatic TCCU in a large unselected population treated according to routine clinical practice. Material and methods: This is a retrospective, observational multicenter Italian trial. 28 italian oncology centers that treated with VFL at least 4 pts from February 2011 to June 2014 have been invited to adhere the trial. Pts were eligible if they have received VFL as a second or third line therapy following a first line treatment containing platinum. Primary objective is to test whether the overall survival (OS) obtained in the registration study are confirmed in the routine clinical practice. Sample size has been determined considering the OS obtained in the registration study, with one-tail test, &agr; 0.05 and 1-&bgr; = 80%, 197 pts have to be enrolled. Results: Overall 217 pts were registered. Median age was 69 yrs (IQR 62-76); 84% were males; ECOG was 0,1,2 in 47%, 46%, and 7%; 21% had liver metastasis. 77% received VFL as second-line and 23% as third-line. The median number of VFL cycles was 4 (IQR 2-6), 29% received an initial dose of 320 mg/m, 35% were treated with 280 mg/m and 36% with a lower dose. Toxicity was manageable, 21% had a grade 3-4: neutropenia (9%), asthenia/fatigue (7%), leucopenia (2%), constipation 5%).Table: C14NoCR (%)PR (%)Median PFS (95% CI)Median OS (95% CI)Registration study2530 (0%)16 (6%)3.0 (2.1-4.0)6.9 (5.7-8.0)Current study2176 (3%)21 (10%)3.2 (2.6-3.7)8.1 (6.3-8.9)Current study (Only pts with PS0-1, and VFL as second line )1576(4%)18(11%)3.3(2.8-4.2)8.3(6.3-8.9)Univariate and multivariate analysis for overall survival (ITT)NoMedian OS (95% CI)Log rank (p)HR (95% CI)pECOG PS 01019.7 (8.1-11.0)15.3 (<0.001)0.61 (0.45-0.81)0.001N. of organs involved =11279.5 (8.0-10.6)15.2 (<0.001)0.66 (0.48-0.89)0.008No liver involvement1718.6 (6.3-9.7)11.2 (<0.001)0.68 (0.47-0.99)0.045 Open table in a new tab Conclusions: The efficacy of VFL was confirmed in this large unselected pts treated according to routine clinical practice. In our multivariate model ECOG PS, liver involvement, the number of involved organs were the main risk factors affecting OS. Hemoglobin level was not significant.