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e18015 Background: PD-L1 is a biomarker of response to anti-PD1 in HNSCC. CA209-7HE trial (NCT04282109) is a randomized, open-label, multicenter, phase II trial including first line R/M HNSCC pts non-eligible for cisplatin-based chemotherapy. Pts were stratified according to Karnofsky performance status, HPV and tissue PD-L1 by Combined Positive Score (CPS). Subjects were randomized to either paclitaxel + nivolumab or paclitaxel + cetuximab. Primary objective was 2-year overall survival. We present the data on centrally determined PD-L1 patterns and its correlation with pt clinical characteristics. Methods: From 176 preliminary samples, only 141 were analyzed. 10 were excluded for not fulfilling quality requirements and 25 belonged to non-eligible pts. 74% (104) were paraffin blocks and 26% (37) tissue slides. 72.3% (102) were primary tumor biopsies, 12.7% (18) local soft tissue relapses, 9.2% (13) lymph node metastases and 5.6% (8) distant metastases. 46.6% (66) were collected from irradiated areas. Hematoxylin-eosin stain confirmed sample representativeness. At least 100 tumor cells/sample was required. Immunohistochemistry for PD-L1 was performed using DAKO PD-L1 IHC 22C3. Means and proportions were dropped for descriptive analyses. Multivariate logistic regresion was used to identify variables associated with higher CPS. Results: Clinical characteristics included 73% (103) males; 77% (108) were either former [56% (78)] or current smokers [21.2% (30)] and clinical stage was recurrent in 48.9% (69), metastatic alone in 29.8% (42) and both recurrent and metastatic in 21.3% (30). Diagnoses included 35.4% (51) oral cavity, 32.3% (45) oropharynx (only 2 pts HPV positive), 16.3% (23) larynx and 15.6% (22) hypopharynx. Mean time to CPS assessment was 5.25 days (CI 95% 4.95 – 5.55). CPS distribution was as follows: 21.7% (31) were CPS < 1, 42.8% (60) were CPS 1-20 and 35.4% (50) were CPS > 20. Multivariate model revealed that oral cavity tumors showed an increased likelihood of CPS > 20 (OR 2.35, 95%CI 1.46 - 3.78; p < 0.001) which was also seen among non-smokers (OR 3.37, 95% CI 1.16 - 9.73; p = 0.02) and pts with recurrent and metastatic disease (OR 2.75, 95% CI 1.03- 7.32; p = 0.04). Oropharyngeal tumors showed lower probability for CPS > 20 (OR 0.35, 95% CI 0.14 - 0.89; p = 0.03). Neither prior irradiation nor origin of the biopsy were associated with any significant variation in CPS. Conclusions: Central assessment of CPS is feasible with no significant treatment delay. HPV negative oropharyngeal tumors were not associated with higher CPS. We also found that oral cavity tumors, non-smokers and pts with recurrent and metastatic disease were independently associated with an increased probability of higher CPS. Future results will elucidate the promising role of combinatorial regimens with immunotherapy in these subpopulations. Clinical trial information: NCT04282109.

6092 Background: Sinonasal cancers (SC) are heterogeneous diseases. Despite multimodality treatment, overall survival (OS) remains unsatisfactory. We aimed to identify prognostic factors (PFs) associated with patterns of failure and OS in non-metastatic SC (nmSC). Methods: We retrospectively reviewed a pooled dataset of nmSC from Princess Margaret (Canada) and Catalan Institute of Oncology (Spain) treated with definitive surgery ± postop radiotherapy (RT) or RT ± chemo according to institutional protocols between 2010-2019. In squamous cell carcinoma (SCC), HPV status was tested by p16 staining, and HPV DNA (ISH or PCR) if equivocal. The primary goal was to assess the association of tumor histology, stage (by 7th edition TNM), and other clinicopathological variables on locoregional control (LRC), distant control (DC) and OS. Actuarial rates were calculated with Kaplan–Meier (KM) method. Multivariable analysis (MVA) calculated hazard ratios (aHR) adjusted for histology type, T-/N-categories, and primary treatment. Results: Out of 342 pts, median age was 62 years (y) (range 21-96), Male:Female = 212:130, 95% had ECOG 0-1. Tumor histology types were: 192 (56%) SCC (p16+: 35; p16-/untested: 157), 40 (12%) adenocarcinoma (AD), 33 (10%) sinonasal undifferentiated carcinoma or sinonasal neuroendocrine tumors (SNUC/SNEC), 28 (8%) malignant melanoma (MM), 27 (8%) esthesioneuroblastoma (ES) and 22 (6%) adenoid cystic carcinoma (ACC). Median follow up was 3.6 y (range 0.1-11.3). Three-year actuarial rates for each endpoint are included in table. The PFs for LRC by MVA were: SNUC/SNEC (vs SCC) histology, T3-4 (vs T1-2: aHR 2.4, p = < 0.01) and N+ (vs N-: aHR 1.7, p = 0.02) diseases. The PFs for DC were: MM (vs SCC) and SNUC/SNEC (vs SCC) histology, and T3-4 (vs T1-2: aHR 6.0, p = 0.01) disease. The PFs for OS were: MM (vs SCC) histology, older age (aHR 1.0, p < 0.01), T3-4 (vs T1-2: aHR 5.6, p < 0.01), and N+ (vs N-: aHR 2.5, p < 0.01) disease. There was no difference in primary surgery vs RT in any outcome endpoint (all p > 0.05). p16+ SCC had a marginally higher LRC but similar DC and OS vs p16-/untested SCC (table). Conclusions: This large multicentre cohort of nmSC shows different patterns of relapse and survival with different tumor histologies. Our results suggest that individualization of treatment and follow-up strategies by histologic type is recommended to optimize outcomes in these orphan diseases. [Table: see text]

TPS6086 Background: Nivolumab is the standard of care for patients (pts) with R/M HNSCC in the platinum-refractory setting. Up to 20% of R/M HNSCC pts are ineligible for cisplatin-based CT due to poor performance status and/or comorbidities. ERBITAX (weekly cetuximab + paclitaxel) is a recommended regimen for this patient population according to the Spanish Society of Medical Oncology guidelines. Preclinical data suggests a role for paclitaxel as immuno-modulator, mainly by increasing tumor infiltrating CD8+ (Galluzzi L., et al 2015). NIVOTAX trial aims to evaluate efficacy and safety of nivolumab + paclitaxel vs ERBITAX as first-line treatment for R/M HNSCC pts with platinum-refractory disease or ineligible for platinum-based chemotherapy. Methods: NIVOTAX (NCT04282109) is a randomized, open-label, multicenter, phase II trial sponsored by the Spanish Group of Head and Neck Cancer Treatment (TTCC) including R/M HNSCC pts not amenable for curative-intent therapy, previously untreated for R/M disease and not candidates for cisplatin-based chemotherapy. Population is distributed in 3 Groups: 1= Platinum-refractory; 2=Platinum-sensitive but unable to receive cisplatin due to: Karnofsky performance status (KPS) 70% and/or major comorbidities (renal/heart failure, grade ≥2 hearing loss) and/or previous allergic reactions to platinum compounds; 3= Platinum-sensitive but cumulative cisplatin dose received ≥225 mg/m² for locally-advanced disease. Pt are stratified according to: KPS (70% vs 80-100%); PD-L1 by Combined Positive Score (CPS ≥1 vs < 1); and HPV positivity (HPV+ oropharynx vs HPV-/non-oropharyngeal). 141 Pt are being randomized 2:1 to NIVOTAX (nivolumab 240 mg q2 weeks + weekly paclitaxel at 80 mg/m2 up to 12 weeks followed by maintenance nivolumab 480 mg/ q4 weeks) or ERBITAX ( weekly 250 mg/m2 plus paclitaxel 80 mg/m2 up to 12 weeks followed by maintenance cetuximab 250 mg/m2 weekly). Both arms will be continued up to a maximum of 24 months. Primary end-point is to evaluate treatment efficacy in terms of 2-year overall survival (2-y OS). It is assumed that 2-y OS in the NIVOTAX arm will be at least 26% (10% gain when compared to the expected 16% 2-y OS rate in this pt population). Secondary objectives include progression free survival (PFS), overall response rate, disease control rate, duration of response, 6m PFS, 5y-OS and safety profile. Response endpoints will be assessed using RECIST 1.1 criteria. As of February 12, 2021, 64 pts have been randomized. Planned safety data review for the first 10 pts treated with NIVOTAX regimen did not show any unexpected AE. Clinical trial information: NCT04282109.

Purpose To assess the activity and toxicity of the combination of gemcitabine plus dacarbazine (DTIC) in patients with advanced soft tissue sarcoma (STS) in a randomized, multicenter, phase II study using DTIC alone as a control arm. Patients and Methods Patients with previously treated advanced STS were randomly assigned to receive either fixed-dose rate gemcitabine (10 mg/m2/min) at 1,800 mg/m2 followed by DTIC at 500 mg/m2 every 2 weeks, or DTIC alone at 1,200 mg/m2 every 3 weeks. The primary end point of the study was progression-free rate (PFR) at 3 months. Results From November 2005 to September 2008, 113 patients were included. PFR at 3 months was 56% for gemcitabine plus DTIC versus 37% for DTIC alone (P = .001). Median progression-free survival was 4.2 months versus 2 months (hazard ratio [HR], 0.58; 95% CI, 0.39 to 0.86; P = .005), and median overall survival was 16.8 months versus 8.2 months (HR, 0.56; 95% CI, 0.36 to 0.90; P = .014); both favored the arm of gemcitabine plus DTIC. Gemcitabine plus DTIC was also associated with a higher objective response or higher stable disease rate than was DTIC alone (49% v 25%; P = .009). Severe toxicities were uncommon, and treatment discontinuation for toxicity was rare. Granulocytopenia was the more common serious adverse event, but febrile neutropenia was uncommon. Asthenia, emesis, and stomatitis were the most frequent nonhematologic effects. Conclusion The combination of gemcitabine and DTIC is active and well tolerated in patients with STS, providing in this phase II randomized trial superior progression-free survival and overall survival than DTIC alone. This regimen constitutes a valuable therapeutic alternative for these patients.

6007Background: Severe Oral Mucositis (SOM) is one of the most significant adverse events (AE) in H&N cancer patients undergoing concurrent chemo/bio-radiotherapy. The objective of the trial is to ...

Purpose To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. Patients and Methods Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m2 given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m2 per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m2 delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). Results Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). Conclusion Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.

11070 Background: The GMI is a marker of drug activity and represents an intra-patient comparison of successive time to progression (TTP), defined as the TTP ratio between the second (or later) line (TTPn) of therapy divided by the prior line (TTPn−1). Defining a clinical profile of pts with GMI >1.33 could help to identify pts who can gain greater benefit from T. Methods: We retrospectively evaluated the concordance between the GMI and the efficacy outcomes and clinical profiles of 198 pts with ASTS treated with trabectedin 1.5 mg/m² (24-h infusion q3w) as a 2nd or further-line treatment from Jan 2007 to Jun 2016. Results: After a median follow-up of 58 months (m; range: 18-172) median overall survival from ASTS diagnosis (MOS) and from T (MT-OS) were 27.5 m (23-32.1) and 10.8 m (8.9-12.7), respectively, while median TTP from T (MT-TTP) and T-1 were 3.4 m (2.8-4) and 3.5 m (2.8-4.2). Overall, 106 pts (53%) had a GMI 1.33. A high GMI (1.33) correlated with favorable efficacy outcomes: MT-OS: 23 vs 36 m (p 8.1 m (2.24, 95%CI 1.19-4.18) and Karnofsky >80 (2.3, 95%CI 1.00-5.28) as factors independently associated to GMI> 1.33. Based on these 3 variables we defined a new GEISTRA score assigning 1 point for each adversely affected variable: non L-Sarcoma, MFI

10524 Background: Risk estimation of recurrence in localized GIST relies on factors as mitosis, size, site or capsule rupture. Recently, genotype has shown to add prognostic value at least in inter...

6037 Background: IC with docetaxel/cisplatin/fluorouracil (TPF) is superior to PF in organ preservation. Bioradiotherapy (BRT) is superior to RT alone in the loco-regional control of locally-advanc...

e20115 Background: Nearly 50% of pts with AM harbor mutations in the BRAF gene which result in activation of the MAPK pathway. BRAF V600 mutations confer sensitivity to BRAF-inhibitors. We aimed to...

10055 Background: The role of surgery of metastasis in GIST patients sensitive to imatinib is controversial. We performed a retrospective analysis of such patients to estimate its potential benefit...

10047 Background: There are scarce and controversial findings published on KNGL series. One of the largest analyzing 26 KNGL found two distinct subsets according to immunostaining (IS): DOG1+ cases...