e16561 Background: The recommended treatment for patients with Stage IV Urothelial carcinoma is first-line platinum-based chemotherapy, followed by avelumab maintenance therapy in patients without disease progression. Real-world evidence (RWE) estimates the number of patients treated and the duration of treatments. Our objective was to assess the effectiveness and safety profiles of these patients in routine clinical practice. Methods: We conducted a multicentric, observational study with retrospective and prospective analysis of patients with stage IV Urothelial Carcinoma who started maintenance therapy with avelumab between January 2021 and April 2022 in 22 sites. Retrospective period included data from deceased patients and from alive patients prior to the signing of the informed consent (IC). Prospective period included patients’ data after signature of the IC. Results: Between September 2022 and July 2023, were enrolled 125 patients, 113 of whom were assessable for the analysis (74 alive and 39 deceased). The mean age was 69.6 years, 85.0% were male. Most of the patients had ECOG 1 (63.4%). Regarding the platinum treatment in first line, 54.0% of patients received cisplatin and 46.0% carboplatin, with a median of 4 cycles administered. Best response to avelumab in the retrospective evaluation was progressive disease (PD) in 25.5%, 43.3% stable disease (SD), 16.4% partial response (PR) and 12.4% complete response (CR). In the prospective period 16.7% reported PD, 54.2% SD, 12.5 PR and 14.6% CR. After a median follow up of 11,9 (8,3) months since the start of avelumab, 21 patients (18.6%) continued with avelumab, with a mean (SD) of 33.0 (12.1) cycles, and 81.4% of patients had stopped, with 12.9 (10.6) cycles administered. 67.3% of patients reported PD or exitus through the follow-up. The progression free survival probability (PFS) as primary endpoint was 0.2140, with a median (95% CI) PFS of 10.1 (7.1 – 12.4) months. The PFS probability at 12 months was 0.4492, with 52.2% of patients reporting PD or exitus. Moreover, 2.6% of patients (n=3) reported an exitus, all of them before 12 months, with an overall survival (OS) probability of 0.9542. The 5.3% of patients had SAEs -one resulted in death- most unrelated to avelumab. 39 patients (34.5%) had a total of 82 adverse drug reactions during the treatment period, 4 of them serious and 45.1% probably related to avelumab. The most frequent ADRs were asthenia and pruritus/rash; no SUSAR was reported. Conclusions: These data agree with the results of the phase 3 JAVELIN Bladder 100 trial and other real-world studies, confirming the effectiveness and manageable safety profile of avelumab 1LM in stage IV UC. Nonetheless, we acknowledge the limitations of our research, including its retrospective design. An extension study is being considered in order to have OS data for 24 months.

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

Anti-programmed death-1 (anti-PD1) treatment has significantly improved outcomes of advanced melanoma with a considerable percentage of patients achieving complete response (CR). This real-world study analyzed the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and evaluated factors related to sustained response. Thirty-five patients with advanced cutaneous or primary unknown melanoma with CR to nivolumab or pembrolizumab from 11 centers were included. Mean age was 66.5 years, and 97.1% had ECOG PS 0-1. 28.6% had ≥3 metastatic sites with 58.8% having M1a-M1b disease; 8.6% had liver and 5.7% had brain metastases. At baseline, 80% had normal LDH, and 85.7% had a neutrophil-to-lymphocyte ratio ≤3. 74.3% of patients had CR confirmed in PET-CT. Median duration of anti-PD1 was 23.4 months (range 1.3-50.5). 24 months after therapy discontinuation, 91.9% of patients were progression-free. Estimated PFS and OS at 36, 48, and 60 months from the start of anti-PD1 were 94.2%, 89.9%, 84.3%, and 97.1%, 93.3%, 93.3%, respectively. Antibiotics use after anti-PD1 discontinuation increased the odds of progression (OR 16.53 [95% CI 1.7, 226.03]). The study confirms the feasibility of elective anti-PD1 discontinuation in advanced melanoma patients with CR and favorable prognostic factors at baseline.

8594 Background: Transcriptomic subtyping holds promise for personalized therapy in SCLC, but intratumoral transcriptomic heterogeneity and its clinical significance remain poorly defined. In this study, we aimed to assess transcription factor defined subtypes within multiple regions of intact tissues and identify gen sets associated with long-term chemo-immunotherapy benefit. Methods: We assessed baseline FFPE tumors from 32 ES-SCLC patients enrolled in the IMfirst clinical trial (EudraCT: 2019-002784-10). We used GeoMx DSP to perform transcriptomic analysis from multiple intratumoral regions of interest (ROIs). We used an assay with +1800 genes (GeoMx CTA) plus custom-designed mRNA probes targeting subtype-defining transcription factors not included in the CTA assay (POU2F3, NEUROD1, and YAP1). Custom probes were quantitatively validated using FFPE cell lines. Results: We profiled 175 ROIs from 32 tumors. Cluster analysis based on the expression of ASCL1, NEUROD1, POU2F3, and YAP1 showed that all samples clustered within 4 groups: SCLC-A (76 ROIs [43%]), SCLC-N (31 ROIs [18%]), SCLC-P (18 ROIs [10%]), and SCLC-Y (50 ROIs [29%]). ASCL1 was the most abundantly expressed transcription factor, prevailed in the SCLC-A subtype, and showed inverse correlation with POU2F3 (r=-0.55, p<0.0001) and YAP1(r=-0.70, p<0.0001). YAP1 was expressed at low levels and was more broadly distributed across all 4 subtypes. Differential expression and gene set enrichment analysis (GSEA) using linear mixed models revealed that SCLC-A subtype was enriched in cell cycle and DNA damage repair genes, and showed repression of multiple gene sets associated with anti-tumor immune response. In contrast, SCLC-Y subtype showed the opposite pattern. The SCLC-P subtype was also enriched in genes related to cancer antigens and T-cell checkpoints. Most patients (n=18, 56%) had tumors with coexistence of more than one subtype, not evident through morphological inspection. Combined SCLC-A and SCLC-Y subtypes was the most common mixed phenotype (n=8, 25%). Four patients (13%) had tumors with co-existence of three subtypes. Transcriptional subtypes, subtype-defining transcription factors as single genes, or the presence of subtype heterogeneity, were not associated with outcomes. Gene sets involved in mitochondrial metabolism and MHC class I antigen presentation were the highest enriched pathways in tumors from patients with sustained benefit (time to progression ³ 12 months). Conclusions: This study reveals substantial intratumoral transcriptomic subtype heterogeneity in human SCLC. In this limited sample set, we did not observe outcome association for transcriptional subtypes. Our findings related to long-term chemo-immunotherapy benefit require validation in independent cohorts.

e21529 Background: Previous reports proved the feasibility of immunotherapy (IT) discontinuation in advanced melanoma (MEL) patients (pts) in case of CR. We aimed to investigate clinical characteristics of pts with sustained CR after elective discontinuation of the 1st line anti-PD1 monotherapy in the real world setting. Methods: This is a multicenter retrospective cohort study. Eligible pts ≥ 18 years with unresectable locally advanced or metastatic primary cutaneous (PC) or unknown primary (UP) MEL with at least one measurable lesion per RECIST version 1.1 at baseline, treated with nivolumab (NIVO) o pembrolizumab (PEMBRO) monotherapy with no previous IT were included. All pts achieved CR to the treatment confirmed by computed tomography (CT) or positron emission tomography (PET-CT) and had at least one imaging study in the follow-up (FU). IT discontinuation was at the discretion of the treating physician. Pts with CR who stopped IT due to toxicity grade (G) 3 and/or 4 were excluded. Information regarding baseline characteristics, survival and immune related adverse events (irAEs) was obtained from patients´ charts. Data cut-off was February 10th 2022. Results: 36 pts treated in 12 hospitals in Spain between October 8th 2015 and October 27th 2021 were identified. Mean age was 66.8 years and mean BMI was 27.4. Twenty eight (77.8%) pts were males and 35 (97.2%) had ECOG PS 0-1. PC melanoma was observed in 33 (91.7%) pts, UP in 3 (8.3%). 35 pts (97.2%) had metastatic disease, with 11 (30.6%) pts with ≥3 metastatic sites. There were 21 (58.4%) pts with stage M1a-M1b disease; only 3 (8.3%) had liver and 2 (5.6%) had brain metastases. Baseline LDH was within normal limits in 28 (77.8%) pts and 31 (86.1%) pts had baseline neutrophil to lymphocyte ratio ≤3. Treatment received: PEMBRO 21 (58.3%), NIVO 15 (41.7%) pts. CR to treatment was confirmed by PET-CT in 27 (75.0%) pts. Median duration of anti-PD1 IT was 23.5 months (range 1.3 - 50.5) and median time to CR was 12.0 months (range 2.2 - 50.2). With the median FU time off treatment of 24.1 months (95% CI 19.4 – 28.8), median progression free survival (PFS) after IT discontinuation has not been reached: estimated PFS at 1 and 2 years were 94.1% and 89.2%, respectively. Estimated overall survival from start of IT at 3 and 4 years were 97.2% and 93.5%, respectively. irAEs G 1-2 were observed in 30 (83.3%) pts and the most common were: vitiligo 8 (22.2%), pruritis 4 (11.1%), other skin toxicity 8 (22.2%), hypothyroidism 5 (13.9%), pneumonitis 3 (8.3%), colitis 5 (13.9%), hepatitis 3 (8.3%), arthralgia 5 (13.9%) and nephritis 3 (8.3%). Conclusions: Our study confirms sustained CR after elective 1st line anti-PD1 monotherapy discontinuation in a cohort of advanced PC and UP MEL pts with favorable established prognostic factors for MEL at baseline. Frequency of irAEs was concordant with previous reports on IT.

PURPOSE:Identifying patient characteristics that define a worse disease prognosis or "high tumor burden" (HTB) status is essential for clinical decision-making and treatment selection in metastatic non-small cell lung cancer (mNSCLC). We aimed to define this concept based on the experience of oncologists in clinical practice.PATIENTS AND METHODS:A representative sample of Spanish experts was selected and asked to complete an online survey regarding the definition of HTB according to their personal experience.RESULTS:HTB was identified by the oncologists (N = 81) as one of the principle factors influencing first-line treatment decision-making. According to the experts, HTB is mainly defined by the number of metastatic lesions (n = 45, 56%), location (n = 34, 42%), tumor size (sum of diameters of target lesions; n = 26, 32%) and liver involvement (n = 24, 30). High lactate dehydrogenase (LDH) levels were also associated with HTB. Almost half of respondents (n = 33, 41%) believed that one metastatic lesion was sufficient to consider a patient as presenting HTB, 72% (n = 58) considered that two were necessary and 99% (n = 80) three. Liver (n = 76, 100%) followed by brain (n = 65, 86%) were the main metastatic sites associated with HTB. Tumor size ranging from 6 cm to 10 cm as well as high LDH levels (three times the upper limit) defined the concept for 82% (n = 62) and 100% (n = 76) of oncologists, respectively.CONCLUSION:In the real-world setting, according to experts, HTB is defined by the number of metastatic lesions, location of metastases, tumor size and by high LDH levels. Given the relevance of this concept, efforts should be made to unify its definition and to further explore its potential as a prognostic factor for mNSCLC patients.

Anaemia is defined by the presence of haemoglobin (Hb) levels < 13 g/dL in men and 12 g/dL in women. Up to 39% of cancer patients present it at the time of diagnosis and up to 40% have iron deficiency. Anaemia causes fatigue, functional deterioration and a reduction in the quality of life; it has also been associated with a poorer response to anti-tumour treatment and lower survival. Basic diagnostic tests for anaemia are simple and should be a routine part of clinical practice. These guidelines review the available evidence on the use of different therapies for treating anaemia: erythropoiesis-stimulating agents, iron supplements, and transfusion of blood products.

Ra223 is a life-prolonging alpha-emitter bone targeted therapy for mCRPC patients with bone metastases. However, evidence on biomarkers that may help us in patient selection are lacking. Total ALP (tALP) appeared to be a potential marker of Ra223 effect in early studies (Sartor, Ann Oncol, 2017). Other bone-related markers, as bone-specific ALP (BALP), have demonstrated its prognostic value in mCRPC patients with bone metastases (Fizazi K, Eur Urol, 2015; Lara PN, J Natl Cancer Inst, 2014).

Pegylated liposomal doxorubicin (PLD) is a drug whose use is increasingly common. It has been associated with a lower rate of haematologic and cardiac side effects than its nonencapsulated form. However, mucocutaneous toxicity is quite frequent and can be severe. Here we provide a case report of a patient who developed an intertrigolike eruption during treatment with PLD.