LDH as prognostic factor in second line treatment for advanced gastric cancer: The LINE study.

person Anna Michelotti Department of Medical Area, University of Udine; Department of Medical Oncology, IRCCS, CRO of Aviano, Udine, Italy info_outline Anna Michelotti, Marco de Scordilli, Elisa Sperti, Roberta Mazzeo, Carla Corvaja, Giacomo Aimar, Lorenzo Gerratana, Michela Guardascione, Federica Rampin, Silvia Buriolla, Paola Di Nardo, Valentina Fanotto, Victoria Andreotti, Michele Bartoletti, Elisa Bertoli, Claudia Noto, Angela Buonadonna, Massimo Di Maio, Elena Ongaro, Fabio Puglisi

Authors person Anna Michelotti Department of Medical Area, University of Udine; Department of Medical Oncology, IRCCS, CRO of Aviano, Udine, Italy info_outline Anna Michelotti, Marco de Scordilli, Elisa Sperti, Roberta Mazzeo, Carla Corvaja, Giacomo Aimar, Lorenzo Gerratana, Michela Guardascione, Federica Rampin, Silvia Buriolla, Paola Di Nardo, Valentina Fanotto, Victoria Andreotti, Michele Bartoletti, Elisa Bertoli, Claudia Noto, Angela Buonadonna, Massimo Di Maio, Elena Ongaro, Fabio Puglisi Organizations Department of Medical Area, University of Udine; Department of Medical Oncology, IRCCS, CRO of Aviano, Udine, Italy, Medical Oncology, Ordine Mauriziano Hospital, Turin, Italy, Department of Oncology, University Hospital of Udine (ASUFC); Department of Medicine (DAME), University of Udine, Udine, Italy, Universita degli Studi di Torino Dipartimento di Oncologia, Torino, Italy, Department of Medicine-Hematology and Oncology, Feinberg School of Medicine, Northwestern University; Department of Medicine (DAME), University of Udine, Chicago, IL, Department of Medical Oncology, Clinical and Experimental Pharmacology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy, Department of Oncology, University of Turin, Ordine Mauriziano Hospital, Torino, Italy, Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Aviano, Italy, Department of Medical Oncology, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano, Italy, Department of Medicine, University of Udine and Department of Oncology, University Hospital of Udine, Udine, Italy, Department of Medicine (DAME), University of Udine; Dipartimento di Oncologia Medica, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, Udine, Italy, Department of Medicine (DAME) - University of Udine, Udine, Italy, Department of Medicine (DAME), University of Udine; Department of Medical Oncology, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), Udine, Italy, Oncologia Medica e Prevenzione Oncologica, Centro di Riferimento Oncologico (CRO), IRCCS, Aviano (PN), Italy, Department of Oncology, Medical Oncology and Cancer Prevention, Centro di Riferimento Oncologico (CRO) di Aviano, IRCCS, Aviano, Italy Abstract Disclosures Research Funding No funding received None Background: Lactate dehydrogenase (LDH) is recognized as indirect marker of tumor hypoxia and angiogenesis for several solid tumors. Ramucirumab is the first antiangiogenic agent approved for second-line therapy in advanced gastric cancer (GC), alone or in association with chemotherapy. To date, no reliable biomarkers can predict the potential benefit from anti-VEGFR2 treatment. This retrospective multicenter study aimed to assess the prognostic role of baseline LDH levels in patients (pts) undergoing second-line treatment for advanced GC. Methods: The study analyzed a retrospective cohort of consecutive advanced GC pts treated with second line therapy at IRCCS, CRO of Aviano and at Mauriziano Hospital of Torino, Italy, from 2010 to 2020. LDH levels prior to second-line treatment were classified as low-normal or high and standardized according to the upper limit of the reference range. To better determine the optimal LDH cut-off value, ROC analysis was performed (using PFS < 3 months as binary outcome). Normalized LDH values were subsequently sorted according to the ROC curve cut-off in order to test the association with overall survival (OS) through the Kaplan-Meier method and compared using the Log-Rank test. A multivariate Cox regression analysis assessed the prognostic impact of normalized LDH levels for OS calculated from the start of second line treatment. Results: Overall, 125 pts were enrolled. Of these, 81 pts (64.80%) received ramucirumab alone or plus paclitaxel as second line treatment, while 44 (35.20%) had taxanes or fluoropyrimidines combined with irinotecan. Median age was 68 years, 93% had an ECOG PS ≤ 1, 64.80% was first diagnosed with metastatic disease and 40.80% underwent primary tumor resection. Median second line PFS and OS were 4.2 and 7.9 months, respectively. Baseline LDH values were available for 99 pts. ROC analysis identified a normalized LDH value of 0.83 as the optimized cut-off point to define pts with poor prognosis. At univariate analyses, surgery of the primary tumor (HR 0.51, 95% CI 0.31-0.82, p = 0.005) was associated with better OS, while low-normal BMI ( < 25 kg/m 2 ) at second line start (HR 1.99, 95% CI 1.21-3.28, p = 0.007), normalized LDH values ≥ 0.83 (HR 1.86, 95% CI 1.13-3.07, p = 0.015) and PS > 1 (HR 5.65, 95% CI 2.29-13.92, p < 0.001) were associated with poorer outcome. At multivariable model, only PS > 1 was independently associated with poor prognosis (HR 9.93, 95% CI 3.27-30.08, p < 0.001). Subgroup analyses showed no significant heterogeneity in OS outcome according to normalized LDH levels between patients treated with or without ramucirumab. Conclusions: Elevated LDH levels are indicators of worse outcome in advanced gastric cancer pts. Notably, the LDH cut-off value identified a poor prognosis subgroup among pts with normal baseline levels, suggesting that current laboratory ranges could be suboptimal for patient stratification.