Background: Targeting the programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) axis has demonstrated clinical benefit in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Combining immunotherapies targeting PD-L1 and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) has shown evidence of additive activity in several tumor types. This phase III study evaluated the efficacy of durvalumab (an anti-PD-L1 monoclonal antibody) or durvalumab plus tremelimumab (an anti-CTLA-4 monoclonal antibody) versus standard of care (SoC) in R/M HNSCC patients. Patients and methods: Patients were randomly assigned to receive 1 : 1 : 1 durvalumab (10 mg/kg every 2 weeks [q2w]), durvalumab plus tremelimumab (durvalumab 20 mg/kg q4w plus tremelimumab 1 mg/kg q4w  4, then durvalumab 10 mg/kg q2w), or SoC (cetuximab, a taxane, methotrexate, or a fluoropyrimidine). The primary end points were overall survival (OS) for durvalumab versus SoC, and OS for durvalumab plus tremelimumab versus SoC. Secondary end points included progression-free survival (PFS), objective response rate, and duration of response. Results: Patients were randomly assigned to receive durvalumab (n ¼ 240), durvalumab plus tremelimumab (n ¼ 247), or SoC (n ¼ 249). No statistically significant improvements in OS were observed for durvalumab versus SoC [hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.72e1.08; P ¼ 0.20] or durvalumab plus tremelimumab versus SoC (HR: 1.04; 95% CI: 0.85e1.26; P ¼ 0.76). The 12-month survival rates (95% CI) were 37.0% (30.9e43.1), 30.4% (24.7e36.3), and 30.5% (24.7 e36.4) for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Treatment-related adverse events (trAEs) were consistent with previous reports. The most common trAEs (any grade) were hypothyroidism for durvalumab and durvalumab plus tremelimumab (11.4% and 12.2%, respectively), and anemia (17.5%) for SoC. Grade !3 trAE rates were 10.1%, 16.3%, and 24.2% for durvalumab, durvalumab plus tremelimumab, and SoC, respectively. Conclusion: There were no statistically significant differences in OS for durvalumab or durvalumab plus tremelimumab versus SoC. However, higher survival rates at 12 to 24 months and response rates demonstrate clinical activity for durvalumab. Trial registration: ClinicalTrials.gov: NCT02369874.

6012 Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874. [Table: see text]

The study objective was to compare the biomechanics of surgically assisted rapid palatal expansion (SARPE) with tooth-borne and bone-borne expanders. Materials include a sample of 54 cone-beam CT of 27 patients who underwent SARPE (bone-borne, n=21; tooth-borne, n=6) before treatment and at expander removal. Expansion efficacy was estimated by interapecal and intercoronal distances between maxillary canines, premolars and first molars as well as Coronal-Apical Index (CAI = coronal expansion (mm)/apical expansion (mm)). CAI varied between 1.5 and 2.0 in the group of patients with bone-borne appliances, and from 2.3 to 2.6 in the tooth-borne appliances group. The maximal amount of vestibular coronal declination was revealed in premolars by the use of tooth-borne appliances. Bone-borne appliances allowed lateralization of maxilla and the most prominent effect of tooth shift in a vestibular direction, which may be seen as the most important factors in a relapse prevention.

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e15505 Background: Inflammation seems to be significant factor in carcinogenesis and tumor progression of numerous cancers. Blood calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), lactate dehydrogenase (LDH), international normalized ratio (INR) can be evaluated as systemic inflammation markers and prognostic biomarker for many aims: survival outcomes, lymph node metastasis and recurrence, treatment responses in a variety of cancers. The purpose of this study was to investigate baseline associations between blood test parameters (NLR, PLR, LDH, CRP, INR) and their prognostic biomarker role for patient with metastatic gastric cancer, undergoing first-line chemotherapy Methods: Potential baseline inflammatory markers (platelets, neutrophils, lymphocytes, the platelet-lymphocyte ratio, the neutrophil-lymphocyte ratio, the serum C-reactive protein [CRP], the serum LDH, INR) were retrospectively analyzed in 32 patients with metastatic gastric cancer, IV stage (median of age – 60,50). Multivariate analyses were used to identify prognostic factors for overall survival (OS). Baseline values were compared with tumor characteristic and median survival times (MSTs). Results: Multivariate analysis identified due to Cox proportional-hazards regression showed significant longest OS in patients with: localization of primary tumor in antral part of gastric (HR 0,45, 95% CI 0,25-0,80, p = 0,0065); low baseline’s level of WBC (HR 1,17, 95% CI 1.02 - 1,35, p = 0,0219); low baseline’s level of neutrophil (HR 1,18, 95% CI 1.02 - 1,34, p = 0,0251). Level of LDH, CRP, INR didn’t show significant ratio for this cohort of patient. Peritoneum metastatic also didn’t significant affect on OS in patient with metastatic gastric cancer. Patients with low baseline’s platelet to lymphocyte ratio (HR 1,004, 95% CI 1,0009-1,0072, p = 0,0125) and low (from 0 to 3,0) neutrophil to lymphocyte ratio (HR 1,81, 95% CI 1,09-2,99, p = 0,0212) had a significantly longest OS time. Conclusions: Inflammatory markers can predict overall survival in stage IV gastric cancer. Simple and useful.

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e15570 Background: Ramucirumab is the first anti-angiogenic targeted agent to demonstrate improved survival as monotherapy or in combination with CT among patients with disseminated stomach cancer. Methods: Under our supervision there were 24 patients: 12 men (50%) and 12 women (50%), from 29 to 72 years old, the median age was 52 years (95% CI 43.56-60.32). The median time to diagnosis of the 4th stage of the disease was 2 months (95% CI 0-11.44). All patients received 1 line of treatment; the median duration of 1-line therapy was 5 months (95% CI 4.00-6.83). Results: The duration of therapy with ramucirumab ranged from 2 to 16 months; median duration was 5.0 months (95% CI 3.00-7.44). The therapy with ramucirumab in 11 patients (45.83%) was followed by SD, in 3 patients (12.50%) - PR, in 4 patients (16.67%) - PD, and in 6 patients (25 , 00%) assessment of the effectiveness of therapy was not conducted due to the deterioration of the general condition during treatment. Thus, the ORR was 58.33%. The median overall survival was 18 months (95% CI 14–23). In order to identify adverse factors affecting overall survival, we constructed a Cox's regression model showing the dependence of overall survival on unfavourable prognosis factors. In general, the constructed model was reliable - p = 0.0013. The gender of the patients (p = 0.0642), the time before staging the 4th stage of the disease (p = 0.4312) and the duration of the 1st line therapy (p = 0.8675) did not have a significant effect on the survival of patients. Such factors as the patients' age (p = 0.0121), the localisation of the primary tumor (p = 0.0441), the differentiation of the tumor (p = 0.0095), the fact of removal of the primary tumor (p = 0.0133) had a significant impact, general status on the ECOG scale (p = 0.0250), the presence of anemia (p = 0.0192), damage to the peritoneum (p = 0.0022) and damage to metastases of more than 3 organs (p = 0.0062). Conclusions: An increase in OS in patients who received a combination of ramucirumab and paclitaxel can be considered clinically significant for this patient population and will allow considering this therapeutic regimen as a new standard of second line treatment of patients with poor prognosis of gastric cancer.

The purpose of the research. To study prognostic significance of indicators of systemic inflammation of peripheral blood and relative indicators: neutrophil‑lymphocytic and platelet‑lymphocytic ratio, the course of squamous cell carcinoma of the oral mucosa and gastric adenocarcinoma.Materials and methods. Prospective analysis of patients with squamous cell carcinoma of the oral mucosa and disseminated gastric adenocarcinoma was performed. Patients with verified diagnosis, without signs of inflammatory diseases in anamnesis, not receiving antibacterial and immunomodulatory therapy were selected. Overall survival and survival without progression were considered as the main estimated parameters.Results. The selection criteria were met by 32 patients with disseminated gastric adenocarcinoma and 60 patients with squamous cell carcinoma of the oral mucosa. The prognostic value of relative indicators is determined: overall survival of patients with gastric adenocarcinoma with a low value of the neutrophil‑lymphocytic index is significantly higher than that of the rest of the cohort of patients: 16 months vs. 8 and 7 months (95 % CI (confidence interval) from 12 to 23 months, p=0.0382). Overall survival of patients with low platelet‑lymphocytic index was also higher: 16 months vs. 8 months (95 % CI from 11 to 24 months, р=0,0026). Different relapse‑free survival was noted in the group of patients with squamous cell head and neck cancer: patients with low index value it is 7 months vs. 2 months (95 % CI from 5 to 9 months, p=0.0499).Conclusions. The results show the possibility of using immunological microenvironment of the tumor and indices, characterizing the systemic inflammation, for prognosis of gastric adenocarcinoma and squamous cell carcinoma of the oral mucosa.