PURPOSE:To determine the safety and efficacy of taselisib, a selective PI3K inhibitor, in combination with tamoxifen. PATIENTS AND METHODS:POSEIDON is a phase II, randomized, placebo-controlled trial conducted from June 2016 to March 2020. Eligible patients were refractory upon prior endocrine therapy. Prior treatment with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and everolimus was allowed. Patients were randomized (1:1) to receive either taselisib (4 mg) + tamoxifen (20 mg) or placebo + tamoxifen. The primary endpoint of the trial was investigator-assessed progression-free survival (PFS) in the intention-to-treat (ITT) population (two-sided α 0.2, 90% power). Exploratory biomarker analysis with regards to prognosis and treatment resistance was conducted in circulating tumor (ct)DNA. RESULTS:POSEIDON met its primary endpoint, in which patients treated with taselisib + tamoxifen had improved PFS compared with patients treated with placebo + tamoxifen in the ITT population (median PFS 4.8 months vs. 3.2 months; stratified hazard ratio 0.69; 80% confidence interval, 0.49-0.98, P = 0.17). However, toxicity of taselisib was significant, with diarrhea (40% any grade) as the most common adverse event. Exploratory analyses indicated that high tumor fraction (TF) determined in ctDNA at baseline is associated with worse PFS and overall survival (P < 0.0001). CONCLUSIONS:Our findings suggest efficacy of PI3K inhibition + tamoxifen beyond second-line treatment and after prior targeted therapies, including CDK4/6 inhibition in metastatic HR+/HER2- breast cancer, although the magnitude of benefit did not outweigh the tolerability of this combination. Exploratory biomarker analysis indicates that TF determined in ctDNA differentiates patients based on prognosis and may help optimize patient selection for targeted treatment strategies.

TPS4124 Background: Moving stage III Colon Cancer (CC) into the precision medicine space is a priority in view of the lack of molecular markers driving adjuvant treatment. Retrospective studies have demonstrated the tremendous prognostic impact of circulating tumor DNA (ctDNA) analysis after curative intent surgery, and suggested that lack of conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy reflects treatment failure. With these premises, we have designed the PEGASUS trial (NCT04259944). Methods: PEGASUS is a prospective multicentric study designed to prove the feasibility of using liquid biopsy (LB) to guide the post-surgical and post-adjuvant clinical management in 140 microsatellite stable Stage-III and T4N0 Stage-II CC patients. The LUNAR1 test (Guardant Health, Redwood City, CA, USA) will be used for ctDNA determination. For the efficacy analysis, the PEGASUS cohort will be compared with a 3:1 matched cohort of 420 patients from the TOSCA trial (NCT00646607). A LB executed 2-4 weeks post-surgery will guide a “Molecular Adjuvant” treatment: i) ctDNA+ patients will receive CAPOX for 3 months and ii) ctDNA- patients will receive capecitabine (CAPE) for 6 months but will be retested after 1 cycle, and if found ctDNA+ will be switched to CAPOX treatment. At the end of the “Molecular Adjuvant” treatment a further LB will be performed and instruct subsequent treatment. Positive patients (ctDNA+/+ and ctDNA-/+) will receive an up-scaled “Molecular Metastatic” systemic treatment for 6 months or until radiological progression or toxicity: i) ctDNA+/+ patients will be treated with FOLFIRI; ii) ctDNA-/+ patients with CAPOX. These patients will be subjected to a LB after 3 months and at the end of treatment: in case of positivity will be switched to FOLFIRI. ctDNA+/- patientswill receive a de-escalated treatment with CAPE for 3 months. 3 LB will be performed within 3 months and in case of positivity the patient will be switched to FOLFIRI. Patients with ctDNA-/- will be subjected to an interventional follow-up comprising 2 further LB and in case of positivity they will be switched to CAPOX treatment. PEGASUS is piggybacked to AlfaOmega (NCT04120935), a Master Observational Protocol that will follow patients from diagnosis to 5 years or recurrence/death (whichever comes first), collecting clinical data, radio-images and biological samples. AlfaOmega provides a clinical and logistic ecosystem for the seamless integration of PEGASUS clinical results with the biological underpinning of colon cancer. Clinical trial information: NCT04259944 .

TPS3647 Background: Circulating tumor DNA (ctDNA) testing has emerged as a transformative tool for detecting molecular residual disease (MRD). Multiple prospective trials have demonstrated the potential of ctDNA in guiding treatment decisions for stage II-III CC pts. Numerous ongoing randomized clinical trials (RCTs) are adjusting adjuvant chemotherapy (ACT) intensity based on MRD status. However, data from ctDNA-guided trials, including PEGASUS (NCT04259944), reveal that intensified ACT is curative in only a small proportion of MRD cases. To address this limitation, the SAGITTARIUS RCT was designed to evaluate whether combining ctDNA detection with targeted agents selected on the basis of tissue-based comprehensive genomic profiling (CGP) can optimize treatment in high risk (i.e. MRD+) pts while sparing low risk (i.e. MRD−) from unnecessary toxicity. Methods: SAGITTARIUS is a Phase III RCT evaluating ctDNA and tissue-guided personalized post-surgical management in resected stage III and high-risk stage II CC pts. Tumor-informed, personalized ctDNA test (Signatera, Natera, Inc.) and CGP (TruSight™ Oncology Comprehensive EU, Illumina, Inc.) are used to determine MRD status and tumor genomic landscape, respectively, including genetic mutation (mut) and amplification (ampl), tumor mutational burden (TMB) and microsatellite instability (MSI) status. Pts are stratified based on post-surgery (3-5 weeks) ctDNA status into two embedded RCTs:Trial-1)ctDNA-positive (ctDNA+) ptsare further stratified based on MSI and RAS/RAF status and randomized 1:1 to standard 6-month ACT (CAPOX/FOLFOX) or personalized treatment (PT) guided by CGP biomarkers with reassessment of ctDNA status to guiding subsequent therapies (chemotherapy regimens in ctDNA+ or maintenance and follow-up in seroconverted; Trial-2) ctDNA-negative (ctDNA−) ptsare randomized 1:1 to a physician-choice strategy or observation with ctDNA reassessed at 2 and 4 months and, in cases of positivity, cross over to Trial-1. PT include 3-month CAPOX followed by FOLFIRI or TEMIRI based on MGMT status (RAS/RAFmut), Ipilimumab + nivolumab (MSI and TMB-high POLEmut), pertuzumab + trastuzumab (HER2ampl), FOLFOX + panitumumab (RAS/RAF/HER2 wild-type). The primary endpoint (EP) is 2-year recurrence-free survival (RFS) in ctDNA+ pts. Secondary EPs include 2-year RFS in ctDNA− pts, 3- and 5-year overall survival, and ctDNA conversion rate. Quality of life and health costs data are collected for cost effectiveness analysis. Biospecimens, including archival tumor tissue, serial blood samples, and buccal swabs, are collected for exploratory analyses. To detect a hazard ratio of 0.6325 for ctDNA-guided PT vs standard ACT, 200 ctDNA+ pts will be randomized in Trial-1. Recruitment began in October 2024 across 26 institutions in Italy, Spain, and Germany. Clinical trial information: NCT06490536 .

Background: Several studies have shown that patients with stage I TNBC derive limited, if any, benefit from chemotherapy. sTILs, a surrogate marker for an active adaptive antitumor immune response, are strongly prognostic and predictive in patients with TNBC across all treatment settings. A recent individual patient-data meta-analysis has shown optimal survival outcomes in patients with stage I TNBC and sTIL ≥ 50% who did not undergo (neo)adjuvant systemic therapy, with a linear association between sTILs and prognosis [Leon Ferré et al, JAMA 2024]. Trial Design: ETNA trial (NCT06078384) is a phase II, open-label, international, multicenter, biomarker-driven study designed to evaluate chemotherapy de-escalation in patients with T1b/c N0M0 TNBC (ER/PgR < 10% by IHC) and sTILs ≥ 30% in resected primary tumors. Eligible patients who have undergone adequate breast cancer surgery will be included in one of two cohorts based on their sTILs levels, as determined by a central review of the surgical specimen. Cohort 1 will include patients aged > 40 years with 30% ≤ sTILs < 50% and those aged ≤ 40 years with 30% ≤ sTILs < 75%. Patients will receive 9 cycles of adjuvant pembrolizumab 200 mg every three weeks and Paclitaxel 80 mg/m2 weekly for 12 doses. Cohort 2 will include patients aged > 40 years with sTILs ≥ 50% and those aged ≤ 40 years with sTILs ≥ 75%, who will undergo standard surveillance without adjuvant systemic treatment. A total of 1728 pT1b/cN0M0 TNBC patients will be screened for inclusion. Based on the TNBC pooled analysis [Leon Ferré et al, JAMA 2024] and the prevalence of young patients < 40 years in the stage I TNBC population of CANTO (10%), we expect 12.5% of screened patients to be eligible for cohort 1 and 8% for cohort 2. The study will enroll 216 patients in cohort 1 and 138 patients in cohort 2. The primary endpoint is 5-year distant disease-free survival in the 2 cohorts. Secondary endpoints include 5-year invasive disease-free survival, distant recurrence-free survival and overall survival, safety analysis, and quality of life evaluations. Cohorts 1 and 2 will be analyzed independently. Ancillary studies will be performed on the surgical and blood samples to explore prognostic biomarkers and obtain a comprehensive description of TILs in patients with early-stage TNBC. Site activation is currently ongoing. Citation Format: Elie Rassy, Stefan Michiels, Magali Lacroix-Triki, Roberto Salgado, Paolo Nuciforo, Fatima Zohra Toumi, Jérôme Lemonnier, Juan Manuel Ferrero-Cafiero, Vittoria Barberi, Susana Muñoz, Isabel Pimentel, Esther Zamora, Maria Borrell, Oliver Tredan, Sophie Pellegrino, Fabrice André, Mafalda Oliveira, Barbara Pistilli. Adjuvant pembrolizumab and chemotherapy or surveillance in Early Triple Negative breAst cancer with high stromal tumor-infiltrating lymphocytes (sTILs) score (ETNA) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-10-26.

Background: Survival of HER2-positive (HER2+) metastatic breast cancer (MBC) patients (pts) has improved with targeted therapies, but there is still a need of developing new therapeutic approaches. Double blockade alone with trastuzumab (T) and pertuzumab (P) showed significant clinical activity. T and P exert part of their activity based on antibody dependent cell mediated cytotoxicity (ADCC), mediated by natural killer cells (NK). Through the binding of the CD16 receptor of the NK cell to the Fc domain of T, NK cells can eliminate tumor cells covered by these antibodies. Furthermore, ADCC activation of an innate immune response induces cytokine secretion and antigen release, which may trigger an adaptive immune response against tumor antigens. Solid tumors usually present poor NK infiltration due to limited homing and immunosuppressive microenvironment. Our hypothesis is that the effect of T and P can be improved by regulating the efficiency of the ADCC activity through the infusion of ex-vivo activated allogenic NK cells. We propose a proof-of-concept phase I clinical trial for pts with HER2+ MBC refractory to antiHER2 therapies, to test the infusion of allogenic NK cells in order to enhance the ADCC of T and P to overcome this resistance and improve clinical outcome. Methods: This is a single arm, open label, multi-center, proof of concept investigator-initiated phase Ib trial to assess the safety and the tolerability of NK adoptive cell therapy (NK-ACT) and T+P when used in combination in refractory HER+ MBC. A total of 6 pts will be included in the safety lead-in phase. If signs of both clinical and biological activity are seen, and no more than 1 treatment-limiting toxicity (TLT) is observed, the study will expand with 14 additional pts. The NK investigational cell product comprises a live cell suspension of allogenic NK cells obtained from peripheral blood from a healthy donor, that will be infused on Day 2 at a minimum dose of 5x107 NK and a maximum dose limit of 5x108 NK. IL-2 will be administered on Days 2 (within 24h after NK infusion), 4 and 6 as a subcutaneous dose of 5x105 UI/m2. A preparative IV single-dose cyclophosphamide (600mg/m2) is given between Days -3 and -5 before NK cell infusion. On day 1, T is given at a dose of 8mg/kg IV for the loading dose, and 6mg/kg IV for the maintenance dose and P at a dose of 840mg IV for the loading dose, and 420 mg IV for the maintenance, both every 3 weeks, until disease progression, unacceptable toxicity or study termination. Major eligibility criteria: HER2+ pts as per ASCO/CAP guidelines; ECOG performance status ≤1; measurable disease; received at least two lines in the metastatic setting including trastuzumab/pertuzumab and an anti-HER2 ADC; progressed to previous therapy; normal organ and marrow function; patient has potential NK allogenic donors. Key exclusion criteria: Prior treatment with adoptive cellular therapy; Symptomatic or untreated primary or metastatic CNS malignancy. The primary objectives are to assess the safety and the tolerability of NK-ACT and T/P when used in combination. The secondary objective is to evaluate the initial clinical activity of NK-ACT concomitant with T/P. Exploratory objectives include describing the mechanisms of action and assessing biomarkers of the immunomodulatory effect and anti-tumor activity of the combination of NK-ACT and T/P. Statistical methods: no formal hypothesis testing and no formal sample size calculation. The safety lead-in phase will include the first 6 pts. If no more than 1 TLT is observed amount those pts, the study will expand with 14 additional pts. Citation Format: Santiago Escrivá-de-Romaní, Vladimir Galvao, Maria Castro-Henriques, Ascensión Lopez-Díaz de Cerio, Aura Muntasell, Carlos Vilches, Miguel López-Botet, Maria del Carmen Ochoa, Susana Inmaculada Inoges, Sara Santana, Marta Rotxes, Pere Barba, Julia Lostes, Gabriela Ene, Sonia Servitja, Guillermo Villacampa, Susana Muñoz, Darío López, Xenia Villalobos, Silvia Martin Lluesma, Cristina Saura, Joan Albanell, Elena Garralda, Ignacio Melero, Maria Martinez-Garcia. A phase Ib study of the safety, tolerability, biological effect, and efficacy of allogenic natural killer cells in combination with trastuzumab and pertuzumab in patients with refractory HER2-positive metastatic breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-12-27.

PURPOSE:Immune checkpoint inhibitors combined with chemotherapy have provided successful results in patients with gastric and gastroesophageal junction (G/GEJ) cancers in the metastatic setting. Similar strategies have been explored in earlier stages. In this study, we present the final results of the phase II MONEO trial, which evaluated the addition of avelumab to neoadjuvant chemotherapy. PATIENTS AND METHODS:Patients with untreated, resectable G/GEJ adenocarcinoma received neoadjuvant treatment with four cycles of avelumab plus the FLOT4 regimen, followed by surgery. Upon postoperative recovery, patients underwent four additional adjuvant cycles of the same combination, followed by avelumab monotherapy for up to 1 year. The primary endpoint was pathologic complete response rate. Sequential flow cytometry and cytokine determination were performed in peripheral blood, along with multiplex tissue immunofluorescence and RNA sequencing in tumor specimens. RESULTS:Forty patients were enrolled, achieving a pathologic complete response rate of 21.1% (95% confidence interval, 10.0-37.0). The major pathologic response rate was 28.9%, more pronounced in patients with tumors expressing PD-L1 before treatment as measured by the combined positive score (cutoff, 10; 33.3% vs. 21.1%). The results propose several potential biomarkers considering tumor immune infiltrate, circulating immune cells, and cytokines. Eighty percent of patients experienced treatment-related grade ≥3 adverse events. CONCLUSIONS:The combination of avelumab plus the FLOT4 regimen showed relatively modest efficacy in resectable G/GEJ adenocarcinoma. Better results were observed in PD-L1 combined positive score ≥10% tumors. Exploratory biomarker analyses provide insights that may help to identify candidates most likely to benefit from chemoimmunotherapy as a neoadjuvant treatment.

TPS2674 Background: Tumors associated with SWI/SNF complex (SWI/SNFc) mutations, mainly SMARCA4 and SMARCB1 loss, are a heterogeneous group of malignancies with rhabdoid features that typically affect young patients (pts). These are aggressive malignancies with poor prognosis for which no standard treatment is available. Despite not having a high tumor mutation burden, tumor infiltrating lymphocytes (TILs) are usually present in high numbers. The biologic reasons for this feature are not clearly understood but might be associated to changes in gene expression due to aberrant chromatin remodeling. However, these TILs indicate that tumor antigens are recognized by lymphocytes unveiling a vulnerability that can be exploited by immunotherapy. The objective of the TILTS study is to develop a personalized adoptive cell therapy using TILs in pts affected by these tumors. Methods: Single arm, multi center, phase 2 study of TILs in pts with advanced tumors associated with SWI/SNFc mutations. Pts are treated at 3 centers in Spain: Catalan Institute of Oncology (ICO), Barcelona, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, and Centro Integral Oncológico Clara Campal (HM CIOCC), Madrid. Primary endpoint is overall response rate (ORR) by RECIST 1.1. Secondary endpoints include toxicity evaluation, duration of response (DOR), progression-free survival (PFS) or overall survival (OS). After informed consent is obtained, tumor resection is performed. Total volume of tumor resected should be at least 1.5 cc to assure TIL isolation. Eligible pts enter the treatment phase. TILs are produced under GMP conditions. During the TILs manufacturing process, pts are allowed to receive standard treatment if clinically indicated. Before TIL infusion, pts receive non-myeloablative preconditioning lymphodepletion with daily intravenous (IV) cyclophosphamide (60 mg/kg; IV x2 doses) and daily fludarabine (25 mg/m2; IV x5 doses). Infusion of autologous TILs is given on Day 0 followed by administration of IL-2 at 600,000 international units (IU)/kg every 8-12 hours for a maximum of 6 doses. After 4 weeks, a new tumor biopsy is optional. First image evaluation is performed after 8 weeks from TIL infusion. Pts without progression enter the follow-up phase. An ancillary translational study will explore mechanisms of immunogenicity, antigen recognition, TILs anti-tumor activity, and changes in the stool microbiome and specific TCR population during treatment. Also, tumor immune microenvironment will be analyzed. Clinical trial information: 2023-504632-17-00 . [Table: see text]

The SWI/SNF complex is a chromatin remodeling complex comprised by several proteins such as SMARCA4 or SMARCB1. Mutations in its components can lead to the development of aggressive rhabdoid tumors such as epithelioid sarcoma, malignant rhabdoid tumor or small cell carcinoma of the ovary hypercalcemic type, among others. These malignancies tend to affect young patients and their prognosis is poor given the lack of effective treatments. Characteristically, these tumors are highly infiltrated by TILs, suggesting that some lymphocytes are recognizing tumor antigens. The use of those TILs as a therapeutic strategy is a promising approach worth exploring. Here, we report the clinical protocol of the TILTS study, a Phase II clinical trial assessing personalized adoptive cell therapy with TILs in patients affected by these tumor types.

TPS4155 Background: GC represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5th of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study. Clinical trial information: NCT03979131.

TPS3151 Background: Basket trials with targeted agents can show high response rates for tumors with specific molecular profiles, granting extension of the label of some drugs. In other cases, study results were disappointing, likely due to the rarity of molecular alterations, limits in trial design and the difficulties in applying molecular tumor profiling in the clinical setting. Methods: Basket of Baskets (BoB), NCT03767075, aims to bridge the gap between Academic Genomics and clinical applications (ready-to market multi-marker Companion Diagnostics) by providing a sustainable and adaptable (to new technologies, markers, and therapeutic agents) platform for co-development of drug/companion diagnostic. BoB is a novel platform trial from Cancer Core Europe, a recently established sustainable European network for innovative cancer research. This protocol has two parts: (1) Part A includes a molecular profiling program for subjects with advanced solid tumors (iPROFILER), a variant annotation tool, and a molecular tumor board to select the most appropriate treatment. It also enables testing/developing companion diagnostics linked with the therapeutic part (part B). (2) Part B includes iBASKET, a modular multi-arm basket trial for subjects with tumors harboing selected molecular alterations. Each module is focused on a certain molecular pathway or on certain molecular alterations that may confer sensitivity to the study drug or study drug combination evaluated in that module/arm. The current version of iBASKET (Module 1- Atezolizumab in genomically-selected patients) is open for enrollment for patients with advanced neoplasms bearing one of the following alterations: Arm 1A: BRCA1 or BRCA2; Arm 1B: MLH1, MSH2, MSH6, PMS2; Arm 1C: POLE, POLD1 mutations; Arm 1D: hypermutated tumors; Arm 1E: other mutations in DNA-repair genes; Arm 1F: PDL1 gene amplification. All patients enrolled in Module 1 will receive single-agent atezolizumab. New Modules for genomically selected populations can be added through amendments. Our final aim is to achieve drug repurposing of treatments, co-develop multi-marker companion diagnostics and a large database of knowledge in Precision Medicine. Clinical trial information: NCT03767075.

El patrón llamado ‘crazy paving’ en tomografia computada de tórax (TAC) puede deberse a diferentes condiciones siendo una de ellas la Proteinosis Alveolar Pulmonar (PAP), rara condición que puede llevar a insuficiencia respiratoria y a menudo, a la muerte. Presentamos el caso de una mujer joven con una historia de un año de evolución de disnea progresiva y tos seca que consultó por un cuadro de aparición brusca de fiebre, calofríos, malestar general y falla respiratoria hipoxémica severa (PaO2 = 51,9 mmHg con FiO2 = 0,50) en la cual la TAC de tórax mostraba un patrón de empedrado o ‘crazy paving’ que significó un desafío diagnóstico resuelto finalmente con una biopsia pulmonar quirúrgica que mostró una PAP. Ante el fracaso del tratamiento tradicional de Lavado Pulmonar Total (LPT) se usó una aproximación terapéutica novedosa consistente en una serie de 4 lavados lobares con un perfluorocarbono, Perflubron (PFC) bajo anestesia local seguido por 5 sesiones de Plasmaféresis. Casi inmediatamente después de este tratamiento la paciente evidenció mejoría radiológica y funcional. La PaO2 fue de 89,9 mmHg respirando aire ambiental y la CVF y el VEF1 aumentaron alcanzado respectivamente el 77 y el 75% de sus valores normales de referencia. Dadas las características químicas y físicas del PFC, pensamos que es una alternativa válida al LPT en estos casos.

Primary Objective• To compare investigator-assessed progression free survival (PFS) between Tamoxifen and placebo versus Tamoxifen in combination with Taselisib at the RPTD.

Abstract Background: The combination of PI3K-AKT-mTOR pathway inhibitors with endocrine therapy can improve clinical outcomes of hormone receptor positive (HR+) metastatic breast cancer (MBC) patients. Taselisib is a potent and selective PI3K inhibitor, with greater selectivity against mutant (MUT) PI3Kα isoforms than wild-type (WT) via a unique mechanism. Phase Ib data of POSEIDON with Taselisib + tamoxifen (TAM) demonstrated encouraging activity in patients with heavily pre-treated MBC, with an acceptable toxicity profile (Baird et al, ASCO 2016). The recommended phase II dose (RP2D) was Taselisib 4mg plus TAM 20mg, both administered on a daily continuous schedule. ctDNA monitoring may have value in drug development by (1) assessing predictive biomarkers to therapy, (2) providing an early indication of treatment response, and (3) shedding light on potential mechanisms of acquired drug resistance. In some patients included in phase Ib of POSEIDON, tumor response was preceded by a corresponding early change in plasma PIK3CA ctDNA levels. Methods: The phase II portion of the POSEIDON trial is a two-arm, randomized, double blind study of Taselisib plus TAM versus placebo (PLA) plus TAM in pre- and postmenopausal women with HR+/HER2- MBC. In the first part of the Phase II, 180 patients will be randomized (1:1) to receive continuous TAM with either Taselisib at the RP2D or PLA until disease progression, unacceptable toxicity or patient / physician decision. Crossover is allowed upon progressive disease in those patients receiving PLA plus TAM, after collection of tumor and blood samples for exploratory biomarker analysis. Stratification is based on menopausal status, histology [lobular breast cancer (LBC) vs. ductal/others], PIK3CA mutation (WT vs. exon 9 vs. exon 20), prior everolimus, timing of recurrence/progression after prior endocrine therapy, number of prior chemotherapy (CT) lines, and treatment center. After recruiting the initial 180 patients, trial will focus in LBC, until a total number of 110 patients with LBC are enrolled. Other key eligibility criteria include presence of measurable or evaluable disease (RECIST 1.1), prior progression to endocrine treatment, maximum of 5 prior CT lines in the metastatic setting, absence of diabetes under medical treatment, and absence of chronic inflammatory bowel disease. Primary endpoint is investigator-assessed PFS. Key secondary endpoints are PFS in LBC, objective response rate, clinical benefit rate, safety, and exploratory biomarker analysis (including ctDNA). The study has a 90% power at a two-sided log-rank test significance level of 0.2 to detect an HR of 0.64, which corresponds to an increase in median PFS from 4.5 months in the PLA plus TAM arm to 7 months in the Taselisib plus TAM arm. Enrollment to POSEIDON Phase II started in June 2016 (Clinicaltrials.gov NCT02285179). Citation Format: Oliveira M, Baird RD, van Rossum AGJ, Beelen K, Garcia-Corbacho J, Mandjes IAM, Vallier AL, van Werkhoven E, Garrigós L, Kumar S, van Tinteren H, Muñoz S, Linossi C, Rosing H, Miquel JM, Schrier M, de Vries Schultink A, Saura C, Gallagher WM, Bernards R, Tabernero J, Cortés J, Caldas C, Linn SC. Phase II of POSEIDON: A phase Ib / randomized phase II trial of tamoxifen plus taselisib or placebo in hormone receptor positive, HER2 negative, metastatic breast cancer patients with prior exposure to endocrine treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-11.

Background : The combination of PI3K-AKT-mTOR pathway inhibitors with endocrine therapy can improve clinical outcomes of hormone receptor positive (HR+) metastatic breast cancer (MBC) patients. Taselisib is a potent and selective PI3K inhibitor, with greater selectivity against mutant (MUT) PI3Kα isoforms than wild-type (WT) via a unique mechanism. Phase Ib data of POSEIDON with Taselisib + tamoxifen (TAM) demonstrated encouraging activity in patients with heavily pre-treated MBC, with an acceptable toxicity profile (Baird et al, ASCO 2016). The recommended phase II dose (RP2D) was Taselisib 4mg plus TAM 20mg, both administered on a daily continuous schedule. ctDNA monitoring may have value in drug development by (1) assessing predictive biomarkers to therapy, (2) providing an early indication of treatment response, and (3) shedding light on potential mechanisms of acquired drug resistance. In some patients included in phase Ib of POSEIDON, tumor response was preceded by a corresponding early change in plasma PIK3CA ctDNA levels. Methods : The phase II portion of the POSEIDON trial is a two-arm, randomized, double blind study of Taselisib plus TAM versus placebo (PLA) plus TAM in pre- and postmenopausal women with HR+/HER2- MBC. In the first part of the Phase II, 180 patients will be randomized (1:1) to receive continuous TAM with either Taselisib at the RP2D or PLA until disease progression, unacceptable toxicity or patient / physician decision. Crossover is allowed upon progressive disease in those patients receiving PLA plus TAM, after collection of tumor and blood samples for exploratory biomarker analysis. Stratification is based on menopausal status, histology [lobular breast cancer (LBC) vs. ductal/others], PIK3CA mutation (WT vs. exon 9 vs. exon 20), prior everolimus, timing of recurrence/progression after prior endocrine therapy, number of prior chemotherapy (CT) lines, and treatment center. After recruiting the initial 180 patients, trial will focus in LBC, until a total number of 110 patients with LBC are enrolled. Other key eligibility criteria include presence of measurable or evaluable disease (RECIST 1.1), prior progression to endocrine treatment, maximum of 5 prior CT lines in the metastatic setting, absence of diabetes under medical treatment, and absence of chronic inflammatory bowel disease. Primary endpoint is investigator-assessed PFS. Key secondary endpoints are PFS in LBC, objective response rate, clinical benefit rate, safety, and exploratory biomarker analysis (including ctDNA). The study has a 90% power at a two-sided log-rank test significance level of 0.2 to detect an HR of 0.64, which corresponds to an increase in median PFS from 4.5 months in the PLA plus TAM arm to 7 months in the Taselisib plus TAM arm. Enrollment to POSEIDON Phase II started in June 2016 (Clinicaltrials.gov NCT02285179). Citation Format: Oliveira M, Baird RD, van Rossum AGJ, Beelen K, Garcia-Corbacho J, Mandjes IAM, Vallier AL, van Werkhoven E, Garrigos L, Kumar S, van Tinteren H, Munoz S, Linossi C, Rosing H, Miquel JM, Schrier M, de Vries Schultink A, Saura C, Gallagher WM, Bernards R, Tabernero J, Cortes J, Caldas C, Linn SC. Phase II of POSEIDON: A phase Ib / randomized phase II trial of tamoxifen plus taselisib or placebo in hormone receptor positive, HER2 negative, metastatic breast cancer patients with prior exposure to endocrine treatment [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT2-01-11.

Introduction: Antiretroviral therapy (cART) has changed the natural history of human immunodeficiency virus (HIV) infection in developed countries, where it has become a chronic disease. In addition, the profile of HIV infected patients is changing to an elderly population with increasing morbidities. This clinical scenario requires a new approach to coordinate the care between health teams responsible for the care of patients. To promote communication, cooperation and optimize the control of HIV infected patients, a multidisciplinary unit called Shared Care Unit (UCC) was created in 2008 among the Hospital Clinic of Barcelona and four primary care centers (CAP). In this unit, doctors and nurses from Primary Care settings and The Infectious Diseases Department from the Hospital, meet each two months to coordinate activities involving teaching, research and assistance in the field of HIV infection. We present now the results of a pilot study undertaken in 2013 for evaluating the shared care unit for HIV stable patients.Objectives: To compare the HIV standard of care (controls) with the care in UCC (cases).Methods: A pilot prospective case-control study with duration of 1.5 years was performed in the Hospital Clinic and three CAPs of the same health district.Inclusion criteria for cases were stable patients (Chronic HIV infection with CD4 above 350 cells/mm3 during the last 6 months and if on ART with an undetectable viral load). Exclusion criteria were HIV-infected adults with current therapeutic failure (defined by detectable viral load on cART or CD4 cell count below 250 cells/mm3), tumours, opportunistic infections, or pregnant women.Control patients were HIV infected patients matched for age, sex, primary care center, use of cART and undetectable viral load at the date of inclusion in the study.HIV care during the 18 months of follow-up was performed in control patients as usual in hospital (3 visits), whilst cases made two visits in CAP and the last one in the Hospital.Variables regarding clinical performance [HIV clinical parameters (CD4 cell count, viral load, opportunistic infections, death] and cART-compliance were evaluated throughout the study follow-up. Adherence was estimated at each clinical consultation by monitoring pharmacy refills and through self-reports and was considered high if the patients take more than 90% of the scheduled medication. Quality of life was evaluated through a questionnaire that has been validated in HIV patients (Mini International Neuropsychiatric Interview (MINI). Psychological and emotional Impact was evaluated using several validated screening questionnaires: the Hospital Anxiety and Depression (HAD) Scale to measure anxiety and depression. A qualitative statement about health services utilization in the study population was registered as well as acceptability and satisfaction with the type or care.Results: 93 patients (31 cases and 62 control patients) were included. The mean age of patients was 42 years, 86% were men, 81% men who have sex with men (MSM) and 29% were foreigners. The CD4 count, viral load and adherence to ART showed no significant differences in both groups. Quality of life, psychosocial assessment, the number of emergency room visits and other specialists was similar in cases and controls. 85% liked UCC and 93% considered in the future continue to use the UCC.Conclusions: A Shared Care Unit of HIV infection between Hospital and Primary Care Centers is possible and in this pilot study has been a safe tool for the clinical management of stable HIV infected patients. Sharing clinical management of stable HIV infection between Hospitals and Primary care centers might be an additional model of care.

El uso de plasma rico en plaquetas (PRP) involucra una compleja red de efectos moleculares que favorecerian la regeneracion tisular, dada la presencia en el de multiples mediadores y factores de crecimiento. Se ha comunicado su uso con exito en implantologia odontologica, cirugia plastica y ortopedia como tambien se ha sugerido su utilidad en la regeneracion de nervios perifericos posterior a trauma. No existe difusion acerca de su uso en patologia respiratoria. Comunicamos nuestra experiencia en el uso de PRP en dano agudo del aparato respiratorio. En esta serie de casos, se trataron 4 pacientes con hemoptisis masiva mediante preparacion de PRP autologo previo al procedimiento e instilacion via endoscopica en el sitio del defecto, con buen resultado inmediato y sin recidiva del sangrado al seguimiento; 1 caso de neumotorax espontaneo con infiltrados pulmonares con fracaso del manejo con sonda endopleural (SEP), que resulto ser una neumonia intersticial con quistes pulmonares en un paciente VIH sero-positivo, instilandose PRP por SEP, reexpandiendo el pulmon a las 72 h; 2 pacientes portadores de fistula respiratoria y 1 paciente portador de ruptura traqueal traumatica, todos con buena respuesta. El uso de productos autologos como PRP ha logrado un favorable rendimiento en todas las situaciones clinicas planteadas, lo que lo situa como una herramienta con notable potencial de desarrollo particularmente en casos que por sus caracteristicas particulares requieren de un manejo minimamente invasivo.