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PURPOSE MicroRNAs (miRNAs) have been evaluated as biomarkers in cancers. Therefore, we aimed to identify a prognostic miRNA signature from The Cancer Genome Atlas (TCGA) database and validate it in the Ramathibodi (RA) locally advanced head and neck squamous cell carcinoma (LA-HNSCC) cohort. METHODS The correlation between candidate miRNAs and the survival of patients with LA-HNSCC in TCGA database was analyzed. A prognostic miRNA signature model was generated that classified patients into high-risk and low-risk groups. This candidate miRNA signature was further validated in the independent RA cohort using droplet-digital polymerase chain reaction. RESULTS In TCGA database, we compared the expression of 277 miRNAs between 519 head and neck squamous cell carcinoma tissues and 44 normal tissues. The expression of hsa-miR-10b, hsa-miR-148b, hsa-miR-99a, hsa-miR-127, hsa-miR-370, and hsa-miR-500a was independently associated with overall survival (OS). Thus, we established the miRNA signature risk score from these six miRNAs and categorized patients into low-risk and high-risk groups. The median OS of TCGA patients was significantly shorter in the low-risk group than in the high-risk group ( P < .001). The six-miRNA signature was further validated in the RA cohort (N = 87). The median OS of the low-risk group was significantly shorter compared with the high-risk group ( P = .03). In multivariate analysis, the six-miRNA signature was an independent prognostic factor for OS in the RA cohort (HR, 1.958; 95% CI, 1.006 to 3.812; P = .048). CONCLUSION We identified a prognostic six-miRNA signature for patients with LA-HNSCC from TCGA cohort and validated it in our independent cohort. However, larger studies are warranted to confirm these results.

6505 Background: 1L P vs E improved OS in PD-L1 CPS ≥20 and CPS ≥1 populations, and led to noninferior OS in the total population, with favorable safety; 1L P+C vs E had superior OS in CPS ≥20, CPS ≥1, and total populations with comparable safety in the phase 3 KEYNOTE-048 study (NCT02358031) in patients with R/M HNSCC. Neither P vs E nor P+C vs E improved PFS in the PD-L1 CPS ≥20, CPS ≥1, or total populations. Here, we present the progression after the next line of therapy (PFS2) to assess the effect of 1L P or P+C and subsequent anticancer therapy on patient outcomes. Methods: Patients with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting were randomly assigned 1:1:1 to P, P+C, or E. PFS2 was defined as time from randomization to objective tumor progression on next-line therapy or death from any cause. PFS2 was estimated using the Kaplan-Meier method as an exploratory outcome confined to those receiving subsequent therapy after 1L P. HR and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate (stratified by ECOG performance status [PS], HPV status, and PD-L1 for CPS ≥1 and total populations; by ECOG PS and HPV status for CPS ≥20 population). Data cutoff: Feb 25, 2019. Results: Of 882 (301 [P]; 281 [P+C]; 300 [E]) treated patients,422 (P: 148 [49.2%]; P+C: 115 [40.9%]; E: 159 [53.0%]) received subsequent anticancer therapy after 1L P, most commonly C (P: 135 [44.9%]; P+C: 88 [31.3%]; E: 102 [34.0%]); EGFR inhibitor (P: 59 [19.6%]; P+C: 37 [13.2%]; E: 19 [6.3%]); and immune checkpoint inhibitor (P: 6 [2.0%]; P+C: 12 [4.3%]; E: 50 [16.7%]); patients may have received more than one type of subsequent therapy. Median PFS2 is reported in Table. Conclusions: In patients with R/M HNSCC, longer median PFS2 was observed in the CPS ≥20 and CPS ≥1 populations for P vs E, and in the CPS ≥20, CPS ≥1, and total populations for P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . [Table: see text]

6530 Background: In the phase 3 KEYNOTE-048 trial ( NCT02358031 ) in R/M HNSCC (N = 882), 1L P vs E showed superior OS in PD-L1 CPS ≥20 and CPS ≥1 populations, noninferior OS in the total population, no PFS benefit, and favorable safety; 1L P+C vs E showed superior OS in CPS ≥20, CPS ≥1, and total populations, no PFS benefit, and comparable safety. Results of P or P+C vs E in incurable recurrent only, metastatic only, and R/M subgroups are shown. The metastatic only and R/M subgroups were combined and classified as metastatic. Methods: Patients with incurable recurrent (local and/or regional node recurrent disease) or metastatic HNSCC were randomly assigned 1:1:1 to P, P+C, or E. OS and PFS were estimated using the Kaplan-Meier method. Hazard ratios and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate stratified by ECOG performance status, HPV status, and PD-L1 status. Data cutoff: Feb 25, 2019. Results: In the incurable recurrent only subgroup (n = 252), median OS was 11.5 vs 12.1 mo (P vs E) and 13.0 vs 11.1 mo (P+C vs E). In the metastatic subgroup (n = 620), median OS was 11.4 vs 9.7 mo (P vs E) and 13.0 vs 10.1 mo (P+C vs E). Median follow-up, OS, and PFS are shown in Table. Treatment-related adverse events (TRAE) in the incurable recurrent only subgroup: 49.4% (P), 94.7% (P+C), and 97.8% (E); grade 3-5 TRAEs rates: 16.0%, 78.7%, and 73.3%, respectively. TRAE rates in the metastatic subgroup: 61.6% (P), 96.4% (P+C), and 96.4% (E); grade 3-5 TRAEs rates: 17.6%, 69.5%, and 67.0%, respectively. Conclusions: P and P+C vs E were efficacious in the metastatic subgroup; in the relatively smaller subgroup of patients with incurable recurrent only HNSCC, the effect was less pronounced. Consistent with the total study population and regardless of disease state, the safety profile was favorable with P vs E and comparable with P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . [Table: see text]

6000 Background: KEYNOTE-048 is a phase 3 study of P or P + chemo (C) vs EXTREME (E) as 1L therapy for R/M HNSCC (NCT02358031). At the second interim analysis (IA2), P significantly improved OS in the PD-L1 combined positive score (CPS) ≥20 and ≥1 populations and had noninferior OS in the total population with favorable safety; P+C significantly improved OS in the total population with comparable safety. We present the protocol-specified final results. Methods: 882 pts with locally incurable R/M HNSCC and no prior systemic therapy in the R/M setting who provided a tumor sample for PD-L1 testing were randomized to P 200 mg Q3W for 24 mo (n = 301), P for 24 mo + 6 cycles of C (cisplatin 100 mg/m2 or carboplatin AUC 5 Q3W + 5-FU 1000 mg/m2/d for 4 d Q3W) (n = 281), or E (cetuximab 400 mg/m2 loading/250 mg/m2 QW + 6 cycles of chemo) (n = 300). OS superiority was tested sequentially for P+C vs E in the CPS ≥20 population, then the CPS ≥1 population, and for P vs E in the total population (superiority thresholds: one-sided P = .0023, .0026, and .0059, respectively). Data cutoff was 25 Feb 2019 (~25 mo after last pt randomized). Results: P+C significantly improved OS vs E in the CPS ≥20 (HR 0.60, 95% CI 0.45-0.82, P = .0004; median 14.7 vs 11.0 mo) and CPS ≥1 (HR 0.65, 95% CI 0.53-0.80, P < .0001; median 13.6 vs 10.4 mo) populations. HR (95% CI) for PFS was 0.76 (0.58-1.01) for CPS ≥20 and 0.84 (0.69-1.02) for CPS ≥1. ORR (P+C vs E) was 42.9% vs 38.2% for CPS ≥20 and 36.4% vs 35.7% for CPS ≥1; median DOR was 7.1 vs 4.2 mo and 6.7 vs 4.3 mo, respectively. P did not significantly improve OS vs E in the total population (HR 0.83, 95% CI 0.70-0.99, P = .0199; median 11.5 vs 10.7 mo). HR (95% CI) for PFS was 1.29 (1.09-1.53). ORR (P vs E) was 16.9% vs 36.0%; median DOR was 22.6 vs 4.5 mo. All-cause gr 3-5 AE rates were 54.7% for P, 85.1% for P+C, and 83.3% for E. Conclusion: Overall, KEYNOTE-048 showed that compared with E, P+C had superior OS in the PD-L1 CPS ≥20, CPS ≥1, and total populations with comparable safety and P had superior OS in the CPS ≥20 and ≥1 populations, noninferior OS in the total population, and favorable safety. These results support pembrolizumab and pembrolizumab + platinum + 5-FU as new 1L standards of care for R/M HNSCC. Clinical trial information: NCT02358031.

6081Background: Impact of age on treatment outcomes of head and neck squamous cell carcinoma (HNSSC) patients. Methods: We retrospectively HNSCC patients treat at Ramathibodi hospital between 1/200...

3063 Background: Entolimod is a specific, TLR5 agonist derived from salmonella flagellin, with immunotherapeutic effects in preclinical cancer models. Entolimod activates innate and adaptive immune responses and mobilizes immunocytes to organs such as liver and bladder, with functional TLR5. A phase 1 trial was undertaken to evaluate entolimod’s safety, tolerability, pharmacokinetics, immunoactivity, and preliminary antitumor activity. Methods: Pts with advanced cancers and ECOG PS of 0-1 were treated at 5 subcutaneous doses (5, 10, 15, 20, 30, 40 µg/day) over a 2-week period. PK/PD samples were obtained pre, and 2, 4, 6, 8, 24 hrs post-dose. Immune function samples were obtained pre and 24 hrs post-dose on days1, 8, 11 and 22. Results: 26 pts (38.4% colorectal cancer [CRC] and 19% NSCLC) were enrolled. Common toxicities were transient hypotension (9 grade 1/4, 7 grade 2/4), hyperglycemia (8 grade 1/4, 6 grade 2/4), and fever (10 grade 1/4, 3 grade 2/4). Three DLTs were observed at 40 µg/day. One pt devel...

6070 Background: Early phase clinical studies showed promising activities of anti-PD1/PD-L1 antibody in squamous cell carcinoma of head and neck (SCCHN). PD-L1 expression is a potential biomarker o...

9647 Background: Several studies showed that ginger powder could reduce chemotherapy-induced nausea and vomiting (CINV). 6-gingerol is a natural compound extracted from ginger. It has an antagonist...

e11508 Background: Docetaxel/carboplatin/trastuzumab (H) (TCaH) and doxorubicin/cyclophosphamide/paclitaxel/H (AC-TH) and its variants are recommended by standard guidelines for neoadjuvant and adjuvant treatments for HER2+ breast cancer. Docetaxel/cyclophosphamide/H (TCyH) has also been used in clinical practice. Tolerability and cardiac safety among these regimens have not been well described. Methods: We retrospectively reviewed HER2+ early stage breast cancer who received neo/adjuvant H at RPCI between 2004-2011. Acute toxicities of different regimens (AC-TH and its variants, TCaH, TCyH) were evaluated. Cardiac events were defined as symptomatic congestive heart failure (CHF) and/or asymptomatic decline of ejection fraction (EF) that resulted in holding H. Results: 177 patients were identified (AC-TH=114, TCaH=39, TCyH=24). Patients who received AC-TH were younger, had less comorbidity, including cardiac history, and received less GCSF support. AC-TH regimens were associated with more febrile neutropenia (FN), grade 3-4 neutropenia, and dose delay (Table). Overall cardiac events were observed in 18% (anthracyclines 14% vs non-anthracyclines 9%; p=0.346). Termination of H was not significantly different between patients treated with anthracyclines (4%) vs non-anthracyclines (2%), nor was the CHF rate (4% vs 6%). Median absolute EF decline was also similar (5% vs 4%). After adjustment for age ≥65, cardiac history, baseline EF

e19568 Background: Adherence to adjuvant chemotherapy (ACT) has been implicated in poor outcomes in early breast cancer (BC). We investigated factors that may contribute to non-compliance (NC) in hormone receptor (HR) negative BC. Methods: 310 HR- patients (pts) who received adjuvant chemotherapy (ACT) at Roswell Park Cancer Institute (RPCI) between 2002 and 2008 were eligible for this retrospective analysis. Patients were categorized as Compliant or Non Compliant (NC). Compliance was subdivided into adequate Tx (AT) and inadequate Tx due to Toxicity (ITT). NC was discontinuation or delays in ACT for reasons other than toxicities. The 3 groups were compared based on baseline characteristics, treatment-related toxicities, and survival. Fisher’s exact, logistic regression, Cox regression, and log-rank tests were used to analyze the data. A significant p value was assigned at ≤ 0.05. Results: 192 pts were included, with a median age of 55 (range 27-86), and median follow up of 4.9 yrs. NC was observed in 19 (10%) pts, ITT in 47 (24%), and AT in 126 (66%). ITT and NC pts were more likely to have a higher Charlson co-morbidity index (CCI) (p=.019), ECOG performance status (p=.048), more hospital stays (p=

1134 Background: US Oncology Research Trial 9735 reported that TC improved overall survival when compared to AC in early stage breast cancer (BC). Despite 61% grade 3-4 neutropenia in TC arm, only ...

e19675 Background: The optimal treatment and expected dental outcome of osteonecrosis of the jaw (ONJ) is not well understood. Dental management is recommended and administered as per a standard gu...