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502 Background: Urothelial carcinoma (UC) commonly affects patients (pts) who are ineligible for full doses of cisplatin-based chemotherapy (CT) due to bad performance status, advanced age, or renal impairment. The combination of split-dose cisplatin with ATZ might be a feasible treatment for pts with UC who are unfit for full doses of cisplatin. Methods: The phase II SOGUG-AUREA clinical trial recruited treatment-naive pts in advanced or metastatic settings considered unfit for full dose of platinum-based CT. Pts received a split dose of cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) days 1 and 8 (up to 6 cycles) in combination with 3-weekly ATZ 1200 mg in D1 intravenously until progression, unacceptable toxicity, or absence of clinical benefit. Here we present the early results from the confirmed objective response rate (ORR) according to RECIST 1.1, the primary endpoint for efficacy, progression-free survival (PFS), overall survival (OS) and safety. Results: Between Jan 2021 and Mar 2022, 82 pts were screened, 66 pts were enrolled and received at least one dose of study treatment. Baseline characteristics are outlined in the table. The median duration of ATZ treatment was 4.4 months (m) (95%CI: 4.1-4.6). The confirmed ORR was 40.9%, with 5 (7.6%) pts having CR and 22 (33.3%) PR. The median duration of the response was 7 m (95%CI: 4.9-10.4). The clinical benefit rate (CBR) was 53%, and SD (maintained > 6m) was reported in 8 (12.1%) pts. Eight (12.1%) pts were not evaluable for response due to exitus previous to disease evaluation (9.1%), non measurable target lesions (1.5%) or withdrawal (1.5%). With a median follow-up of 9.3 m (range: 0.6-18.1), the median PFS was 6.9 m (95%CI: 6.4-9.2), with a 6-m PFS rate of 67.1% (95% CI: 56.5-79.7). The reasons for platinum ineligibility did not correlate with PFS. The 6-m OS rate was 78.2% (95%CI: 68.6-89). Most frequent grade 3-4 toxicities were neutrophil count decreased (24.2%), anemia (21.5%) and platelet count decreased (13.6%). Conclusions: ATZ with split doses of CT was safely administered in a population of frail pts with mUC who were unfit for CT showing promising preliminary survival outcomes in terms of response. Final survival results are awaited. Clinical trial information: NCT04602078 . [Table: see text]

TPS4589 Background: First-line cisplatin-based chemotherapy (70 mg/m2) is the standard of care for LA/mUC patients (pts). However, about 50% will be ineligible for Cisplatin according to Galsky´s criteria. Moreover, a significant proportion of cisplatin-fit pts will receive carboplatin based on physician criteria. s-GC represents a feasible alternative in such situations, and could improve response rate compared to carboplatin regimens. Atezo is a programmed death-ligand 1 (PD-L1) inhibitor that is approved as first line treatment for cisplatin-ineligible LA/mUC pts with PD-L1 expression ≥5% (Ventana SP142). We present the study design of a phase II single arm trial of Atezo +s-GC in previously untreated pts with LA/mUC (NCT04602078). Methods: This single arm, open-label, multicenter study evaluates the efficacy and safety of Atezo +s-GC in previously untreated pts with LA/mUC. 66 pts will be enrolled and receive s-GC x 6 cycles (Cisplatin 35mg/m2 + Gemcitabine 1000mg/m2 on days 1 and 8 Q3W) and Atezo (1200 mg IV Q3W), followed by Atezo (1200 mg IV Q3W) until disease progression, toxicity or absence of clinical benefit. Eligibility criteria include histologically confirmed unresectable LA/mUC, measurable disease per RECIST 1.1 and adequate organ and marrow. Pts must be unfit for full cisplatin dose based on: age > 70 years, PS ECOG 0-2, creatinine Clearance >30 and 12 months prior to inclusion), prior autoimmune disease and uncontrolled significant illnesses. The primary endpoint is ORR per RECIST 1.1 assessed by investigator; the secondary endpoints are DoR, OS, PFS and safety. Biomarker analysis, including PD-L1 expression and microbiome relationship, will be an exploratory objective. The first two patients were enrolled in February 2021. Clinical trial information: NCT04602078.

267 Background: Optimal sequencing of new androgen-receptor targeted agents (ART) abiraterone and enzalutamide with docetaxel (DOC) and cabazitaxel (CABA) is unknown. In this large retrospective cohort of mCRPC patients (pts) treated with CABA after docetaxel (DOC), we evaluated the impact of 3 different sequences: DOC → CABA (group 1, n = 267) Or DOC → ART → CABA (group 2, n = 183) Or DOC → CABA → ART (group 3, n = 124). Methods: Records of 574 consecutive mCRPC patients were retrospectively collected in 44 centres in 6 European countries (France, Spain, UK, Greece, Poland, Turkey) from August 2012 to July 2016. Disease history and clinical characteristics at initiation of DOC therapy and outcomes were collected. Factors influencing OS were evaluated using multivariate stepwise logistic regression. Results: At DOC initiation, median age was 67 years, 83% of pts were ECOG 0-1, 45.1% had pain and 10.8% had visceral metastases. Median number of DOC cycles was 7 (6 in group 2, 7 in groups 1 and 3). Median number of CABA cycles was 6 (6 in groups 1 and 2, 7 in group 3). Median duration of ART treatment was 5.9 and 4.4 mths in groups 2 and 3, retrospectively. Median OS from first DOC cycle were 30.1, 37.1 and 40.1 mths in groups 1, 2 and 3, respectively. Factors influencing OS are summarized in the table below. Conclusions: Results of this retrospective cohort suggest that patients receiving DOC → CAB → ART show the greatest OS. High baseline PSA, short response to first-ADT and clinical progression of pts are major prognostic factors of OS at DOC initiation. The window of opportunity for chemotherapy should not be missed. [Table: see text]

e16088 Background: New emerging therapies for mCRPC, such as CBZ, have prompted the need to identify appropriate patients (pts) for each specific treatment. Updated data on the experience with CBZ ...

e12028 Background: Magnetic Resonance Imaging (MRI) is accepted as the best exploration to predict pathological response to neoadjuvant chemotherapy(NAC) in breast cancer. Our goal is to analyze th...

3526 Background: Anti-EGFR drug resistance is a major challenge in metastatic colorectal cancer (mCRC). The aim of this study was to elucidate molecular mechanisms of acquired resistance in mCRC patients treated with cetuximab-based therapy. Methods: 37 mCRC patients with acquired resistance to cetuximab-based therapy with paired tumor samples (prior and at progression to treatment) were prospectively included. In three patients, multiple biopsies were obtained over the course of the disease. Mutations in EGFR, KRAS, NRAS, BRAF and PIK3CA genes were evaluated by next-generation pyrosequencing. Gene amplification was evaluated by FISH. Mutations were also assessed in plasma in 7 representative cases. Results: Eighty-one percent of patients harbored a molecular event (comprising mutations and amplifications) in post-treatment biopsies. In one third of patients, multiple molecular events (range 2-5) coexisted in the same sample. RAS mutations were the most frequent event (40% of patients) and mostly affected...

235 Background: New emerging therapies for metastatic castration resistant prostate cancer (mCRPC), such as cabazitaxel (CBZ), have prompted the need to identify appropriate patients (pts) for each specific treatment. We describe preliminary data on the experience with CBZ in patients (pts) with mCRPC in Spain. Methods: Medical records from docetaxel-resistant mCRPC pts receiving CBZ at 15 centers in Spain were reviewed retrospectively. Baseline characteristics, PSA response, overall survival (OS), radiographic progression-free survival (rPFS), and toxicity were collected. Results: Data from 79 consecutive pts (median age 70) were reviewed: Eastern Cooperative Oncology Group (ECOG) zero to one (87.3%), Gleason score of 7 to 10 (87.1%), visceral involvement (24.1%), pain (74.7%), and radiological progression (68.4%) at CBZ initiation. Median duration of response to first-line androgen deprivation therapy was 20.8 months (mo). Most pts received less than or equal to two hormonal lines (72.2%) and only one docetaxel line (74.7%) before CBZ. Thirty-five (44.3%) pts had progressed on docetaxel. Progression less than six mo or greater than six mo after last docetaxel treatment was observed in 23 (29.1%) and 21 (26.6%) pts, respectively. New hormonal agents (abiraterone or enzalutamide) were given before CBZ in 2.5% of pts and after CBZ in 17.7%. Pts received a median of seven cycles (range 2 to 22) of CBZ. CBZ dose-reductions or -delays for any cause occurred in eight (10.1%) and 20 (25.3%) pts, respectively. Prophylactic G-CSF was given in 32 (40.5%) pts. A PSA decrease of greater than or equal to 50% and greater than or equal to 30% was reached in 41.2% and 48.6% of pts treated with CBZ. Median OS from first CBZ cycle was 16.2 [CI: 10.4;-] mo and median clinical and/or radiographic progression-free survival (rPFS) was 9.9 mo [CI: 7.4; 13.1]. Fourteen (17.7%) pts experienced at least one grade greater than or equal to 3 treatment-related AE, the most common being neutropenia (n=4), febrile neutropenia (n=2), asthenia (n=4), and diarrhoea (n=2). No grade greater than or equal to 3 peripheral neuropathy was reported. An analysis of factors predicting outcome will be presented. Conclusions: CBZ administered in real-life practice and in the adequate treatment setting in Spain is associated with meaningful PFS and OS and an acceptable safety profile. Dose delays and reductions were low. Prophylactic G-CSF use in 4 out of 10 pts may have contributed to these good results.