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Introduction Cisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies. Methods and analysis Oncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety. Ethics and dissemination The study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov (NCT03674424).

4517 Background: Nearly half of the patients (pts) diagnosed with non-metastatic muscle invasive bladder cancer are unfit for cisplatin therapy and no alternative options of neoadjuvant treatment exist. Avelumab (A), a monoclonal antibody directed against PD-L1, showed efficacy in advanced urothelial cancer. We report preliminary data assessing preoperative avelumab associated with paclitaxel and gemcitabine or avelumab alone in the cisplatin ineligible cohort. The results of the cisplatin eligible cohort were reported at ESMO 2021. Methods: AURA is a prospective, multicenter, randomized, phase II trial for pts with cT2-4aN0-2M0 bladder carcinoma. Pts were enrolled in two separated cohorts based on eligibility for cisplatin chemotherapy. Cisplatin ineligible pts received 4 cycles of paclitaxel-gemcitabine (PG) plus A every 2 weeks or 4 cycles of A every 2 weeks (1:1). Primary endpoint was pCR rate (ypT0/isN0) with the objective, in each arm, to show pCR rate > 5% (90% power reached in case of pCR rate > 25%). Two-step design was used with planned interim analysis after 12 evaluable pts per arm. Secondary endpoints were pathologic downstaging rate ( < ypT2N0) and safety. Results: A total of 56 cisplatin-ineligible pts were evaluable. For PG + A arm (n = 28): median age was 72 years (41-80), 93% male. For A alone arm (n = 28): median age was 75 years (49-89), 93% male. One patient did not undergo surgery due to progression in the A arm but was included in intention to treat analysis. Five pts did not receive the 4 cycles of treatment; reasons included toxicity (n = 3) for PG + A arm and patient/physician decision (n = 2) for A arm. pCR was achieved in 5 pts (18%; 95%CI 6%-37%) treated with PG + A and 10 pts (36%; 95%CI 19%-56%) treated with A. Downstaging to < ypT2N0 was achieved in 6 pts (21%; 95%CI 8%-41%) and 11 pts (39%; 95%CI 22%-59%), respectively. Median time from treatment initiation to surgery was 82 days (55-144) for PG + A arm and 67 days (38-89) for A arm. Most common irAEs of any grade were asthenia (15%), skin toxicity and myalgia/arthralgia (each 5%). There were 2 pts in the PG + A arm with grade 3 irAEs (hepatitis and pneumonitis) that caused A discontinuation for 1 patient. No treatment-related deaths were reported. Conclusions: Neoadjuvant single agent avelumab resulted in high pCR and was safely administered without compromising surgical resection. Our results suggest that the addition of taxane-gemcitabine regimen to avelumab may reduce avelumab efficacy with low pCR rate. Survival analysis and correlative studies are underway. Clinical trial information: NCT03674424.

TPS2066 Background: Better knowledge on the evolving epidemiology and biology of CNS metastases are key elements for the development of new treatment strategies and identification of promising therapeutic targets. A multidisciplinary Brain Metastases Clinical Research Platform called BrainStorm was launched by the Jules Bordet Institute and the Oncodistinct network. The BrainStorm program includes mainly patients with non-CNS metastatic solid tumors with high risk of developing CNS metastases allowing to build a large database focusing on three time periods: before the diagnosis of CNS metastases (Part A), at diagnosis (Part B) and after the diagnosis of CNS metastases (Part C). Methods: Subjects with newly diagnosed non-CNS metastases or up to 24 months from diagnosis of non-CNS metastases from triple-negative and HER2-positive breast cancer, lung cancer and melanoma are eligible for part A of the program. Subjects presenting with a 1st CNS event and not yet enrolled (previously mentioned cohorts and a cohort of other tumor types) can enter directly in parts B and subsequently part C of the study. Eligible subjects are followed for 48 months for relevant clinical data, neurological examinations, quality of life, survival status, and undergo examinations and samplings (Table 1). A total of 280 subjects (40 per cohort) with a 1st CNS event will be enrolled. The main objectives of the program are to collect clinical and biological data with the aim to identify risk factors for CNS metastases development (Part A) and to better understand the biology of CNS metastases (brain and leptomeningeal –Parts B and C) aiming to discover new targets for therapy and intensify the multidisciplinary approach for the management of CNS metastases from solid tumors. The translational part of the program will evaluate among others the use of cerebrospinal fluid circulating tumor DNA (CSF-ctDNA) as a surrogate for CNS metastases in order to characterize its molecular landscape. Currently, the study is recruiting in several sites within the Oncodistinct network. The data collected will help to develop innovative multidisciplinary research projects that could be implemented in all parts of the BrainStorm program. Clinical trial information: NCT04109131. [Table: see text]

Haemangiopericytoma is a rare tumor of vascular origin. We report the case of patient with severe refractory anaemia due to peripheral destruction of red blood cells by spleen metastases. Anaemia was successfully treated by splenectomy. Afterwards, our patient developed liver and lung metastases and was treated, in a clinical trial, with gefitinib that stabilised the disease during nine years. These interesting features are discussed.