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Kaplan-Meier curves for the duration of disease-free survival in joined cohorts with stage II CRC as to adjuvant treatment.

Low densities of FoxP3+ and CD3+ TILs, and their combination, to predict disease-free survival (DFS) in stage II MSS CRC Validation set.

The densities of CD3+ and CD8+ tumor-infiltrating lymphocytes (TILs), combined with tumor–node–metastasis (TNM) staging, have prognostic value for patients with nonmetastatic colorectal cancer. We compared the prognostic value of CD3+ and FoxP3+ TILs at the invasive front, TNM classifiers, and microsatellite (MS) status in a trial set of patients with stage II and III colorectal cancer (n = 413), by recursive partitioning with a classification and regression tree (CART). Significant prognostic factors and interactions were reassessed by logistic regression and Cox proportional-hazards modeling in the trial and a validation set (n = 215) of patients with stage II colorectal cancer. In the trial set, CART indicated that TIL numbers were of value only in predicting recurrence risk for stage II cancers, where low densities of FoxP3+ TILs ranked first and low densities of CD3+ TILs further stratifying risk. Multivariate analysis showed that TILs interacted with tumor stage (FoxP3+, P = 0.06; CD3+, P = 0.02) and MS instability (MSI; FoxP3+; P = 0.02). In stage II MS-stable cancers, concomitant low densities of both FoxP3+ and CD3+ TILs identified patients with the highest progression risk in the trial [HR 7.24; 95% confidence interval (CI), 3.41–15.4; P < 0.001] and the validation (HR 15.16; 95% CI, 3.43–66.9; P < 0.001) sets. FoxP3+ and CD3+ TIL load in colorectal cancer was more informative than other prognostic factors before the cancer progressed to lymph nodes. This prognostic information about TILs, including FoxP3+ cells, suggests that randomized controlled trials might be refined to include interactions between TNM status, molecular classifiers, and postsurgical treatments.

Densities of FoxP3+ and CD3+ TILs in validation set (161 stage II CRC), by clinical-pathological variables.

Densities of FoxP3+ and CD3+ TILs in 413 stage II-III CRC, by clinical-pathological variables.

ROC curves for densities of FoxP3+ and CD3+ TILs as predictors of postsurgical recurrence in patients with stage II MSS CRC, validation set.

Predictors of post-surgical recurrence in 413 CRC patients with stage II/III CRC.

Supplementary Tables S1-S6_S17-S18

Supplementary Figures

In tumor-bearing mice, cyclic fasting or fasting-mimicking diets (FMD) enhance the activity of antineoplastic treatments by modulating systemic metabolism and boosting antitumor immunity. Here we conducted a clinical trial to investigate the safety and biological effects of cyclic, five-day FMD in combination with standard antitumor therapies. In 101 patients, the FMD was safe, feasible, and resulted in a consistent decrease of blood glucose and growth factor concentration, thus recapitulating metabolic changes that mediate fasting/FMD anticancer effects in preclinical experiments. Integrated transcriptomic and deep-phenotyping analyses revealed that FMD profoundly reshapes anticancer immunity by inducing the contraction of peripheral blood immunosuppressive myeloid and regulatory T-cell compartments, paralleled by enhanced intratumor Th1/cytotoxic responses and an enrichment of IFNγ and other immune signatures associated with better clinical outcomes in patients with cancer. Our findings lay the foundations for phase II/III clinical trials aimed at investigating FMD antitumor efficacy in combination with standard antineoplastic treatments.Significance:Cyclic FMD is well tolerated and causes remarkable systemic metabolic changes in patients with different tumor types and treated with concomitant antitumor therapies. In addition, the FMD reshapes systemic and intratumor immunity, finally activating several antitumor immune programs. Phase II/III clinical trials are needed to investigate FMD antitumor activity/efficacy.This article is highlighted in the In This Issue feature, p. 1

Supplementary Methods

Supplementary Table S7-S16

Signaling consequences of treatment with trastuzumab, lapatinib and their combination in HER2-positive colorectal and gastric cancer cells: Effects on downstream transducers.

This files describes supplementary materials and methods

Supplementary Tables

Supplementary Figure S3

Quantitations of phosphoproteins in cell lines and tumorgrafts treated with HER2/EGFR small-molecule inhibitors and antibodies.

Purpose: Preclinical studies in HER2-amplified gastrointestinal cancer models have shown that cotargeting HER2 with a monoclonal antibody and a small molecule is superior to monotherapy with either inhibitor, but the underlying cooperative mechanisms remain unexplored. We investigated the molecular underpinnings of this synergy to identify key vulnerabilities susceptible to alternative therapeutic opportunities.Experimental Design: The phosphorylation/activation of HER2, HER3, EGFR (HER receptors), and downstream transducers was evaluated in HER2-overexpressing colorectal and gastric cancer cell lines by Western blotting and/or multiplex phosphoproteomics. The in vivo outcome of antibody-mediated HER2 blockade by trastuzumab, reversible HER2 inhibition by lapatinib, and irreversible HER2 inhibition by afatinib was assessed in patient-derived tumorgrafts and cell-line xenografts by monitoring tumor growth curves and by using antibody-based proximity assays.Results: Trastuzumab monotherapy reduced HER3 phosphorylation, with minor consequences on downstream transducers. Lapatinib alone acutely inhibited all HER receptors and effectors but led to delayed rephosphorylation of HER3 and EGFR and partial restoration of ERK and AKT activity. When combined with lapatinib, trastuzumab prevented HER3/EGFR reactivation and caused prolonged inhibition of ERK/AKT. Afatinib alone was also very effective in counteracting the reinstatement of HER3, EGFR, and downstream signaling activation. In vivo, the combination of trastuzumab and lapatinib—or, importantly, monotherapy with afatinib—resulted in overt tumor shrinkage.Conclusions: Only prolonged inhibition of HER3 and EGFR, achievable by dual blockade with trastuzumab and lapatinib or irreversible HER2 inhibition by single-agent afatinib, led to regression of HER2-amplified gastrointestinal carcinomas. Clin Cancer Res; 21(24); 5519–31. ©2015 AACR.

Analysis of gene expression and RT-qPCR data in strata of class of response: hyperprogressors (HP), progressors (P), stable disease (SD) and reponders (R).

Supplementary Materials and Methods highlighted

Signaling consequences of afatinib monotherapy and comparison with lapatinib: Duplicate blots for HER receptors.

Purpose: Gene expression profile was analyzed in 68 stage I and 15 borderline ovarian cancers to determine if different clinical features of stage I ovarian cancer such as histotype, grade, and survival are related to differential gene expression.Experimental Design: Tumors were obtained directly at surgery and immediately frozen in liquid nitrogen until analysis. Glass arrays containing 16,000 genes were used in a dual-color assay labeling protocol.Results: Unsupervised analysis identified eight major patient partitions, one of which was statistically associated to overall survival, grading, and histotype and another with grading and histotype. Supervised analysis allowed detection of gene profiles clearly associated to histotype or to degree of differentiation. No difference was found between borderline and grade 1 tumors. As to recurrence, a subset of genes able to differentiate relapsers from nonrelapsers was identified. Among these, cyclin E and minichromosome maintenance protein 5 were found particularly relevant, as their expression was inversely correlated to progression-free survival (P = 0.00033 and 0.017, respectively).Conclusions: Specific molecular signatures define different histotypes and prognosis of stage I ovarian cancer. Mucinous and clear cells histotypes can be distinguished from the others regardless of tumor grade. Cyclin E and minichromosome maintenance protein 5, whose expression was found previously to be related to a bad prognosis of advanced ovarian cancer, appear to be potential prognostic markers in stage I ovarian cancer too, independent of other pathologic and clinical variables.

Supplementary Data from Analysis of Gene Expression in Early-Stage Ovarian Cancer

Effects of anti-HER2 therapies in additional HER2-amplified patient-derived colorectal cancer tumorgrafts.

Signaling consequences of treatment with trastuzumab, lapatinib and their combination in HER2-positive colorectal and gastric cancer cells: Duplicate bots for HER receptors.

Generation and biological characterization of HER2-overexpressing DiFi and HDC-142 cells.

Fluorescence in situ hybridization (FISH)

Signaling consequences of afatinib monotherapy and comparison with lapatinib: Effects on downstream transducers.

Background: At the last update of the TERAVOLT registry, patients with thoracic malignancies and COVID-19 showed a high mortality rate (35.5% overall and 31% due to COVID-19) compared to the general population and to other solid tumors. Major determinants of mortality were age, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), and previous administration of chemotherapy. No cancer-specific data are available with respect to small-cell lung cancer (SCLC) and other rare thoracic malignancies. Methods: TERAVOLT is an international, multicenter observational registry launched to collect data on patients with thoracic malignancies diagnosed with COVID-19 infection. Risk factors for hospitalization and mortality were identified by Wilcoxon rank sum tests (continuous variables) or χ2 tests (categorical variables). Here we present the subgroup analyses of SCLC and other rare thoracic malignancies, including malignant pleural mesothelioma (MPM), thymic carcinoma/thymoma, and carcinoid/neuroendocrine lung tumors. Results: As of June 4th, 2020, a total of 581 patients with COVID-19 and thoracic cancers have been entered; among them, 66 (11%) were SCLC, 22 (4%) were MPM, 18 (3%) were thymic carcinoma/thymoma, 12 (2%) were carcinoid/neuroendocrine lung tumors, and 442 (76%) NSCLC; 21 were an unknown type. Among SCLC patients, 54% were > 65 years old, 56% were males, 98% were current/former smokers, 31% had an ECOG-PS ≥ 2, 67% had stage IV disease, 82% were on current oncologic treatment at the COVID-19 diagnosis, and 58% were receiving chemotherapy alone or in combination with immune checkpoint inhibitors. Among other non-NSCLC patients, 56% were > 65 years old, 56% were males, 69% were current/former smokers, 24% had an ECOG-PS ≥ 2, 50% had stage IV disease, 52% were on current oncologic treatment at the COVID-19 diagnosis, and 37% were receiving chemotherapy alone or in combination with immune checkpoint inhibitors. Overall, 79.7% of the patients required hospitalization, 15.4% were admitted to an ICU, and 39.8% died (36.2% due to COVID-19). Among SCLC patients, 74.2% required hospitalization, 14.3% were admitted to an ICU, and 42.2% died (37.5% due to COVID-19). Among SCLC patients, age > 65 years old (p=0.81), gender (p=0.71), smoking status (p=1.0), ECOG-PS ≥ 2(p=0.17), disease stage of IV (p=0.37), and having received chemotherapy alone or with checkpoint inhibitors (p=0.84) were not associated with mortality. Conclusions: This analysis confirmed that patients with thoracic malignancies have a high mortality and risk for hospitalization due to COVID-19 overall. SCLC patients showed the highest mortality rate among thoracic cancer patients. Citation Format: Alessio Cortellini, Anne-Marie C. Dingemans, Oscar Arrieta, Javier Baena, Matteo Brighenti, Enriqueta Felip, Marina Chiara Garassino, Pilar Garrido, Carlo Genova, Federica Grosso, Leora Horn, Li-Ching Huang, Jan Van Meerbeeck, Solange Peters, Ernest Nadal, Jacobo Rogado, Yu Shyr, Marcello Tiseo, Valter Torri, Annalisa Trama, Heather Wakelee, Jennifer G Whisenant, Giuseppe Viscardi, Fabrice Barlesi, Sanjay Popat. Thoracic cancers international COVID-19 collaboration (TERAVOLT): Small-cell lung cancer and other rare thoracic malignancies [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2020 Jul 20-22. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(18_Suppl):Abstract nr S12-03.

Background: Breast cancer (BC) is the most frequent tumor in women worldwide. BC lethality is caused by aggressive, therapy-resistant metastases (mBC). Preliminary data have shown that mBC lesions are invariably embedded into a densely packed network of fibrous extracellular matrix, making the metastatic microenvironment a potent inducer of mechanical inputs, ultimately leading to the activation of the transcription factors YAP/TAZ. Aberrant mechano-signaling could thus represent a vulnerability of metastasis, which can be exploited to develop new therapeutic strategies. To investigate how metastatic outgrowth is regulated by the physical properties of the microenvironment, and how the altered mechano-transduction of human BC metastasis can be exploited to define new unconventional therapies, we designed and activated METAMECH, a Master Observational Trial (MOT). MOTs are trial constructs hybridizing a canonical observational trial with a multiplex sample-collection platform, aimed to empower the bi-directional collaboration between pre-clinical and clinical research, an essential prerequisite to feed and implement precision oncology. Methods: METAMECH (IFOM-CPO007/2019/PO006) is a MOT that will follow a stage-mixed cohort of at least 500 BC patients throughout their course of treatments, until death or a minimum of 5 years. METAMECH has been designed to streamline the study of the co-evolutionary landscape between tumor and host cells across all BC subtypes. METAMECH is a resource for integrative clinical and imaging data and fresh and archival sample collection which will allow to auction mechanotransduction mechanisms supporting the outgrowth of human metastases, mine for new potentially actionable targets and permit the selection of appropriate patients for mechano-biology experimentally-driven trials. METAMECH is a multi-tiers research scaffold that will allow to integrate the clinical and basic aspects of the project, to optimize patients enrollment and the logistic of longitudinal collection of theirs data/samples. A customized data lake is being designed for data storage, analysis and retrieval. To facilitate patients access, METAMECH has been designed as a flexible infrastructure organized in TIERS, which allow to pursue different objectives: TIER0/1, Retrieving/Recording: to retrospectively and prospectively access to selected cohorts of clinically annotated BC samples to validate/discover mechanotransduction-linked biomarkers and create a mechano-classifier; TIER2, Modelling: to develop pertinent experimental models to study the aberrant mechanisms underlying the metastatic outgrowth and define mechanotransduction-targeting therapeutic strategies; TIER3, Linking: to access data and samples of patients enrolled in Proof-of-Concept trials to prove the efficacy and study/understand resistance mechanisms of mechanotransduction-targeting therapies. Citation Format: Paolo Luraghi, Luca Lazzari, Maria Vittoria Dieci, Serena Bellani, Chiara Soffientini, Rosario Rizzuto, Antonio Rosato, Vincenzo Costanzo, Giorgio Scita, Giannino Del Sal, Massimiliano Pagani, Marco Foiani, Claudio Tripodo, Silvio Bicciato, Giovanni Blandino, Alberto Zambelli, Valter Torri, Matteo Fassan, PierFranco Conte, Silvia Marsoni, Stefano Piccolo. METAMECH -A Master Observational Trial empowering mechanobiology translational research and mechanobased proof of concept trials in breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT261.

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 (EudraCT 2019-002074-32) to prove the feasibility of using liquid biopsy to guide the post-surgical and post-adjuvant clinical management of early colon cancer patients. Methods: PEGASUS is a prospective multicentric vanguard study designed to test the feasibility of performing serial interventional liquid biopsies (LB) for ctDNA determination in 140 microsatellite stable Stage-III and T4N0 Stage-II CC patients. The LUNAR1 (Guardant Health, Redwood City, CA, USA) will be used for ctDNA determination. For the efficacy analysis, the PEGASUS cohort will be compared with a cohort of 420 patients from the TOSCA trial (NCT00646607) population matched 3:1 for all known prognostic phenotypes. A post-surgical LB executed 2-4 weeks after surgery will guide a “Molecular Adjuvant” treatment as follows: 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. Immediately after the end of “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 as follows: 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 and in case of positivity will be switched to FOLFIRI. Patients experiencing ctDNA conversion to negative (ctDNA+/-) will 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. Citation Format: Elena Elez, Filippo Pietrantonio, Andrea Sartore-Bianchi, Clara Montagut, Andres Cervantes, Stefania Sciallero, Maria Giulia Zampino, Stefania Mosconi, Valter Torri, Noelia Tarazona, Luca Lazzari, Paolo Luraghi, Susana Muñoz, Matteo Fassan, Enzo Medico, Livio Trusolino, Maria Rescigno, Salvatore Siena, Alberto Sobrero, Roberto Labianca, Josep Tabernero, Alberto Bardelli, Sara Lonardi, Silvia Marsoni. Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT263.

Background: Clinical trials for HER2-positive metastatic BC excluded pts with prior AdjT and/or relapsing within 1 year (yr) from the end of AdjT. With this gap in mind, we aimed to address the presentation, the therapeutic options, and the clinical outcome of BC pts after failure to AdjT. Methods: Medical charts of BC pts relapsing on AdjT and admitted at the National Cancer Institute of Milan were reviewed. Fisher's exact test was used for contingency tables, long-rank test for survival distribution; p Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-22.

BACKGROUND: Choice of chemotherapy is a major problem in locally advanced (LABC) or metastatic BC pts already treated with anthracyclines and taxanes, or not suitable for these drugs. VNB and CAPE are two valid options, both tested as single agents or in combination in this setting of pts. Different studies have demonstrated that the metronomic treatment could achieve a significant rate of clinical response with an acceptable toxicity profile. Based on the results of metronomic Phase I/II trial, which fixed the dose of VNB at 60 mg/tot thrice a week and considering that the two drugs have a different safety profile, we designed a dose-finding study, aiming to determine the optimal dose of oral VNB in combination with CAPE, both administered in a metronomic way. PATIENTS AND METHODS: Fixed dose of CAPE was 500 mg thrice a day, continuously. Level I dose of VNB was 20 mg/tot, three times a week for 3 weeks (1 cycle); subsequent cohorts started with 30 mg/tot Level II), 40 mg/tot (Level III) and 50 mg/tot (Level IV), respectively, if no Grade 3-4 toxicity was observed in the same dose level of the previous cohort. Results: Twelve consecutive pts were enrolled. Median age was 67.5 years (49-81), 4 pts were LABC or metastatic at diagnosis, HR status was positive in 11/12 pts (91.6%), 2 pts were HER2+ but could not or no longer receive antiHER2 agents due to cardiac failure. All pts but 2 (83.3%) received anthracyclines, taxanes or both. Mean number of metastatic sites was 3 (1-5). At the 50 mg level of dose, 1 pt developed G3 neurological toxicity during the 3rd week of cycle 1 and 1 pt G4 neutropenia in the 2nd week of cycle 2. No pts treated with the 40 mg level of dose experienced G3 toxicity. The Maximum Tolerated Dose (MTD) was fixed at 40 mg thrice a week. CONCLUSION: MTD of metronomic full-oral schedule of VNB in combination with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the further ongoing Phase II study. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-10.

BACKGROUND Eribulin is a synthetic analogue of halichondrin B which inhibits microtubule dynamics. It has been approved in Europe for the treatment of locally advanced or metastatic breast cancer (mBC) progressed after at least two chemotherapy regimens for advanced disease. The most common adverse events (AEs) were fatigue, neutropenia and peripheral neuropathy, which occurs with an incidence ranging from 13.9% to 35%. It was severe only in a small proportion of patients, suggesting an individual susceptibility. The neurotoxicity mechanisms associated with microtubulin interfering agents have not been fully defined. Few studies reported an association between some SNPs (Single Nucleotide Polymorphisms) and microtubulin interfering agents-induced neuropathy, mainly taxanes. As the use of Eribulin becomes more widespread, a better knowledge of its safety profile, outside of clinical trials, is warranted. Given that Eribulin toxicity can result in treatment discontinuation, the ability to anticipate which patients will experience severe toxicity could allow for either early intervention or even possibly for prophylactic therapy, or for a better selection of patients eligible for treatment. METHODS This is a multicenter, interventional, single-arm, phase IV study. The primary objective is the evaluation of the safety and tolerability profile of Eribulin in an unselected population of patients with mBC. Secondary objectives are the description of compliance to treatment and efficacy. ENDPOINTS •Incidence, time of onset, severity and duration of all AEs experienced during treatment with Eribulin, especially the most common reported in previous studies but also other possible unexpected toxicities. •Association between a set of selected SNPs and the onset of any grade peripheral neuropathy. Specifically, 15 SNPs located in genes involved in microtubule dynamics or resulted from genome wide association studies, will be analyzed. •Evaluation of quality of life during treatment using validated questionnaires. •Assessment of dose intensity and dose schedule maintenance. •DOT (Duration Of Treatment) and OS (Overall Survival). STATISTICAL METHODS Summary statistics will be used in order to describe patient characteristics. Safety endpoints will be estimated by means of absolute and relative frequencies and associated 95%CI. The relationship between baseline variables and the risk of severe toxicity, as well as the relationship between SNPs and risk of neuropathy will be described by means of contingency tables and their association with outcome will be assessed by χ2 test of Mantel-Haenzel and a logistic regression model. DOT and OS will be described using Kaplan-Meier curves. A sample size of 200 patients will also allow us to get a good fitting for statistical analysis of the relationship between primary endpoint and not more than 10 factors. Regarding the relationship between SNPs and risk of neuropathy it will be feasible to screen for association about 10-15 SNPs, with known prevalence >15%. PRESENT ACCRUAL AND TARGET ACCRUAL 98 of 200 patients were enrolled until 18/05/2016. Target accrual is open for 200 patients. CONTACT INFORMATION Nicla La Verde: nicla.laverde@asst-fbf-sacco.it. Citation Format: La Verde N, Moretti A, Damia G, Paternò E, Santini D, Garrone O, Fabi A, Ciccarese M, Cretella E, Torri V, Generali D, Grasso D, Puglisi F, Collovà E, Roila F, Bertolini A, Barni S, Vici P, Luigi C, Scandurra G, Bramati A, Dazzani MC, Farina G. PAINTER: Evaluation of eribulin tolerability and correlation between a set of polymorphisms and neuropathy in patients with metastatic breast cancer [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 OT1-01-05.

BACKGROUND: Lactate dehydrogenase (LDH) is a key enzyme in the glycolytic metabolism, especially in anaerobic condition. High serum levels at baseline seem to be a negative prognostic marker in many tumor types, as well a negative predictive marker for response to treatment with anti CTL4 antibodies(Ipilimumab)in Malignant Melanoma. Recently, the treatment of several advanced tumors with anti PD-1 or PDL-1 monoclonal antibodies (mAbs) showed better outcome in comparison to Ipilimumab. However, biomarkers for a proper selection of responding patients is not yet available. The aim of this study is to correlate LDH serum level at baseline with clinical outcome in patients (pts) with advanced solid tumors treated with anti PDL-1 and anti PD-1 mAbs. MATERIAL AND METHODS: We evaluated baseline LDH serum level in 145 pts affected by advanced solid tumors, treated at our Institute with anti PDL-1 and anti PD-1 mAbs. The rate of clinical responses and progression free survival (PFS) were related to normal or elevated baseline LDH serum level. We stratified the pts in 4 groups: normal value (group A),up to 1.5 x ULN (group B); < 2 > 1.5 x ULN (Group C); > 2 x ULN (Group D). We defined as disease control (DC) any complete (CR) and partial response (PR) or stable disease (SD) lasting > 3 months. Correlation between LDH serum levels and DC was assessed by Fisher's exact test; PFS was estimated using the Kaplan-Meier method. RESULTS: We evaluated a heterogeneous population of 145 patients: 73 pts with lung cancer (50.3%; 67 NSCLC, 6 SCLC); 32 pts with Melanoma (22%) and 40 pts (27.6%) with other solid tumors (8 urothelial, 7 biliary tract, 6 mesothelioma, 4 head and neck, 4 sarcoma, 3 gastric, 3 colon, 2 RCC, 1 thyroid, 1 ovarian, 1 HCC). 79 pts (54.5%) were treated by anti PD-1 and 66 (45.5%) by anti PDL-1 agents. Overall as “best response”, 79 pts (54.5%) achieved DC (1 CR, 26 PR, 52 SD) and 66 pts (45.5%) had progressive disease (PD). DC was achieved in 41/79 (52%) pts treated by anti PD-1 and 38/66 (58%) pts treated by anti PDL-1: only 2/41 (5%) and 5/38 (13%) of them had high LDH levels at baseline, respectively. Among 107 pts in Group A, 72 (67.3%) achieved DC as compared to 7/38 pts (18.4%) with high levels of LDH (Group B-D) (p: 0.0001). In the latter groups, PD occurred in 17/23 (74%), 5/6 (83%) and 9/9 (100%) patients in the B, C and D group respectively. CONCLUSIONS: According to this preliminary analysis high baseline LDH serum levels seems to predict a greater likelihood of obtaining worse clinical outcome in terms of response and PFS also in patients treated by anti PD-1 and anti PDL-1 mAbs. In order to confirm this interesting result, we are evaluating a greater number of patients treated with anti PD-1 and anti PDL-1 mAbs at our Institution. Citation Format: Maria Silvia Cona, Valter Torri, Massimo Di Nicola, Marina Garassino, Michele Del Vecchio, Sara Cresta, Diego Signorelli, Silvia Damian, Matteo Duca, Alice Indini, Monica Niger, Filippo de Braud. Baseline LDH serum level as predictive value of activity in patients treated with anti PD-1 and PDL-1 monoclonal antibodies. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3943.