Immune-checkpoint inhibitors (ICI) have revolutionized the therapeutic landscape of cancer. However, optimal patient selection is still an unmet need. One-hundred-forty-six patients with metastatic cancer candidates to ICI at the Hospital Clinic of Barcelona Clinical Trials Unit were prospectively recruited in this observational study. Blood samples were collected at different timepoints, baseline LIPI score calculated and pre-ICI archived tissues retrieved to evaluate PD-L1, tumor-infiltrating lymphocytes (TILs) and PD1 mRNA levels. Tumor assessments were centrally reviewed by RECIST 1.1 criteria. Associations with overall response rates (ORR), durable clinical benefit (DCB), progression-free survival (PFS) and overall survival (OS) were performed with univariable/multivariable logistic and Cox regressions, where appropriate. At a median follow-up of 26.9 months, median PFS and OS were 2.7 and 12.9 months. Response rates were 17.8% with duration of response (DOR) of 4.4 months. LIPI score was independently associated with PFS (p = 0.025) and OS (p < 0.001). Immunotherapy-naïve status was independently associated with better PFS (p = 0.005). Time-to-best response (TTBR) and ORR (p < 0.001 both) were associated with better OS at univariate analysis. PFS and DOR were moderately correlated with OS (p < 0.001 both). A PD-L1 10% cut-off detected worse/best responders in terms of ORR (univariate p = 0.011, multivariate p = 0.028) and DCB (univariate p = 0.043). PD1 mRNA levels were strikingly associated to complete responses (p = 0.021). To resume, in our prospective observational pan-cancer study, baseline LIPI score, immunotherapy-naïve status, cancer type and RT before starting ICI were the most relevant clinical factors independently correlated with immunotherapy outcomes. Longer TTBR seemed to associate with better survival, while PD1 mRNA and PD-L1 protein levels might be tumor-agnostic predictive factors of response to ICI and should be furtherly explored.

In advanced HER2-positive (HER2+) breast cancer (BC), the new antibody-drug conjugate trastuzumab deruxtecan (T-DXd) is more effective compared to trastuzumab emtansine (T-DM1). However, T-DXd can have significant toxicities, and the right treatment sequence is unknown. Biomarkers to guide the use of anti-HER2 therapies beyond HER2 status are needed. Here, we evaluated if pre-established levels of ERBB2 mRNA expression according to the HER2DX standardized assay are associated with response and survival following T-DM1. In ERBB2 low, medium, and high groups, the overall response rate was 0%, 29% and 56%, respectively (P&lt;.001). ERBB2 mRNA was significantly associated with better progression-free survival (p = 0.002) and overall survival (OS; P = 0.02). These findings were independent of HER2 IHC levels, hormone receptor, age, brain metastasis and line of therapy. The HER2DX risk-score (P=.04) and the immunoglobulin (IGG) signature (P=.04) were significantly associated with OS since diagnosis. HER2DX provides prognostic and predictive information following T-DM1 in advanced HER2+ BC.

e17066 Background: Identifying high-risk early-stage EOC patients (p) is a major issue. Also, controversy about the role of neoadjuvant chemotherapy prior to surgery in advanced EOC is still ongoing. A high MLR is related to poorer outcomes in several cancers, and also in ovarian cancer according to limited retrospective series. We explored the clinical value of MLR in a cohort of EOC p. Methods: We included all EOC p diagnosed in our center, from January 2008 to April 2017, who had undergone radical treatment. Overall survival (OS) was assessed by Kaplan Meyer. Maximally selected rank statistics was used to determine the MLR cut-off value for the greatest OS discrimination. The hazard ratio (HR) of death of MLR was explored by multivariate Cox regression models, adjusted by age at diagnosis, stage I/II versus (vs) III/IV, high grade serous carcinomas (HGSC) vs other, primary surgery vs interval surgery after neoadjuvant chemotherapy (PS, IS), residual disease < 1 vs > 1cm, year of diagnosis, and hemoglobin, neutrophils, platelets and MLR at diagnosis. Results: 124 p were included. Median age at diagnosis was 58.7 years; 55.6% were HGSC;67.7% stage III/IV; 69.3% received PS; 14.3% had residual disease > 1cm. Median OS was 75 months. MLR was the laboratory parameter that more significantly impacted on OS in our model (p = 0.02). Optimal MLR cut-off was 0.38. The MLR > 0.38 group (MLR-hi) had a higher-risk of death (HR = 2.9; 95% IC: 1.3–6.5) with respect to those with MLR < = 0.38 (MLR-lo). Median OS were 100 and 35 months, respectively. In the MLR-lo group, median age at diagnosis was 56.9 years (vs 61.9 in the MLR-hi, p 0.047), 44.8% were HGSC (vs 61.2%, p 0.134), and 49.97% were stages I/II (vs 14.2%, p 0.001). MLR-hi p who had undergone PS or IS had similar OS (p = 0.63). In contrast, among MLR-lo p, PS showed significantly higher OS than IS (p < 0.0001). Conclusions: In our cohort, MLR was an independent prognostic factor in EOC. Its potential role to identify high-risk early-stage p and to predict worse outcomes after PS among advanced-stage p need to be explored in larger cohorts.