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Background Immune cells (ICs) infiltration and immune checkpoints have been shown to be important for BC patients’ (pts) prognosis and response to immunotherapy. We aimed to analyze the relation between TILs prevalence and PD-L1 expression with efficacy to an immunostimulatory combination with P and Gem in ABC HER2-negative pts previously treated with ≤4 chemotherapy and/or ≥2 hormone therapy lines from the PANGEA-Breast trial (NCT03025880). Methods Pre-treatment (ttm) metastatic BC samples were assessed for TILs density [% of occupied stromal area upon H&E staining] and for PD-L1 immunohistochemistry expression using monoclonal anti-PD-L1 antibody clone 22C3 (Merck) by calculating ICs score (% of positive infiltrated ICs) and combined positive score [CPS; PD-L1 stained cells (tumor cells, lymphocytes, macrophages) divided by total viable tumor cells, multiplied by 100]. Cut-offs ≥5%, ≥10%, ≥30% were explored for TILs. PD-L1 scores were considered positive if ≥1%. Cut-offs (≥5%, ≥20%, ≥50%) were additionally assessed for PD-L1 as CPS. Logistic regression models were used to evaluate association between TILs density and PD-L1 expression with ttm efficacy in terms of Objective Response Rate [ORR; Complete + Partial Response (CR + PR)], Clinical Benefit Rate [CBR; CR + PR + Stable Disease ≥24 weeks] and Progression Free Survival (PFS), according to RECIST v1.1. Results Thirty-six pts were included, 58% had triple negative BC and 98% ECOG score ≤1. Median number of prior ttm lines was 4. ORR and CBR were 15.2% and 17%, respectively; median PFS was 3.1 months. TILs and PD-L1 were evaluated in 30 and 29 pts, respectively. No association was found between TILs density and ttm efficacy in terms of ORR, CBR and PFS. Analysis of PD-L1 ICs score did not reveal any significant association with ORR, CBR or PFS. However, pts with negative PD-L1 expression by CPS ( Citation Format: Luis De la Cruz, María Gion, Josefina Cruz, Jose Luis Alonso, Vanesa Quiroga, Fernando Moreno, Marta Santisteban, Raquel Andrés, Esther Holgado, Natalia Palazón, Luz Milva Rodríguez, Asunción Soto, Javier Cortés, Alfonso Cortés, Manuel Ramos, Maribel Casas, Massimo Chiesa, Susana Bezares, Rosalía Caballero, Federico Rojo. Association of tumor infiltrating lymphocytes (TILs) density and PD-L1 expression with pembrolizumab (P) plus gemcitabine (Gem) efficacy in patients with HER2-negative advanced breast cancer (ABC) from the GEICAM/2015-04 (PANGEA-Breast) study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-38.

The PANGEA-Breast trial evaluated a new chemo-immunotherapeutic combination that would synergistically induce long-term clinical benefit in HER2-negative advanced breast cancer patients. Treatment consisted of 21-day cycles of 200 mg of pembrolizumab (day 1) plus gemcitabine (days 1 and 8). The primary objective was the objective response rate (ORR). The tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumor, and the myeloid-derived suppressor cells (MDSCs) level in peripheral blood, were analyzed to explore associations with treatment efficacy. Considering a two-stage Simon’s design, the study recruitment was stopped after its first stage as statistical assumptions were not met. A subset of 21 triple-negative breast cancer (TNBC) patients was enrolled. Their median age was 49 years, 15 patients had visceral involvement, and 16 had ≤3 metastatic locations. Treatment discontinuation due to progressive disease (PD) was reported in 16 patients. ORR was 15% (95% CI 3.2–37.9). Four patients were on treatment &gt, 6 months before PD. Grade ≥3 treatment-related adverse events were observed in 8 patients, where neutropenia was the most common. No association was found between TILs density, PD-L1 expression or MDSCs levels and treatment efficacy. ORR in TNBC patients also did not meet the assumptions, but 20% were on treatment &gt, 6 months.

Introduccion El objetivo de neustro trabajo es analizar la seguridad, tolerabilidad, respuestas y supervivencia en pacientes con linfoma no Hodgkin agresivo administrando ciclofosfamida, doxorrubicina, vincristina y prednisona (CHOP) con intensificacion de dosis.

e14589 Background: To know the prevalence of mutations in the RAS family in our hospital, and to determine the effect of new mutations in KRAS and NRAS in overall survival and progression-free surv...

11038 Background: Adjuvant therapies shown survival improve of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). Bisphosphonates are effective agents for the management of osteoporosis. Intravenous zoledronate, which is approved for the treatment of malignant hypercalcemia, multiple myeloma, and skeletal metastases, can suppress bone resorption and are often considered first-line therapy for the treatment of osteoporosis. We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before adjuvant therapies intravenous bisphosphonates (zoledronic acid). Methods: We prospectively studied the effects of a single intravenous zoledronic acid dose (4 mg), on BMD of 74 women with NMBC (stage I-III), administred previous to the adjuvant therapies. The patients were referred to the Medical Oncology Service of University Hospital of Canary Islands between 2003 y 2006. Lumbar and hip BMD (g/cm2) was measured at diagnosis and after chemotherapy. The results were compared with a group of 80 patients with NMBC who received adjuvant therapy without intravenous bisphosphonates. Results: Breast cancer patients the median age was 52 ± 10 years old and the body mass index was 28,2 ± 5.5 kg/m2. At baseline there were not differences in BMD between the group that received bisphosphonates and the group with only chemotherapy at any of lumbar or femoral bone sites. In our study, the BMD after chemotherapy and intravenous bisphosphonates (n=74) significantly increased at femoral neck (0.805 ± 0.01, 0,826± 0.12; p=0.002) and trochanter (0.709 ± 0.01, 0.724 ± 0.01; p=0.002) and remained stable at lumbar, intertrochanter, total hip and Ward’s triangle; whether the group without bisphosphonates significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p=0.0001), trochanter (0.701± 0; 0.690 ± 0, p=0,046), intertrochanter (1,095 ± 0; 1.078 ± 0, p=0.0001) and total hip (0,924 ± 0; 0.915 ± 0, p=0.046) areas (table). Conclusions: Women with NMBC are affected by early bone loss after adjuvant chemotherapy. Bisphosphonates intravenous (zoledronic acid) given before adjuvant therapy might be an effective treatment for this bone loss, increasing BMD or remaining stable. No significant financial relationships to disclose.