Moon Jung Fenton

NCCN Guidelines Insights: Head and Neck Cancers, Version 2.2017

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panels discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Effect of Adding Motolimod to Standard Combination Chemotherapy and Cetuximab Treatment of Patients With Squamous Cell Carcinoma of the Head and Neck: The Active8 Randomized Clinical Trial.

Importance Immunotherapy for recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) is promising. The toll-like receptor 8 (TLR8) agonist motolimod may stimulate innate and adaptive immunity. Objective To determine whether motolimod improves outcomes for R/M SCCHN when combined with standard therapy. Design, Setting, and Participants The Active8 study was a multicenter, randomized, double-blind, placebo-controlled clinical trial enrolling adult patients (age ≥18 years) with histologically confirmed R/M SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx between October 2013 and August 2015. Follow-up ended September 2016. Analysis for the present report was conducted between June 2016 and December 2017. Interventions Combination treatment with platinum (carboplatin or cisplatin), fluorouracil, cetuximab (the EXTREME regimen), and either placebo or motolimod, each administered intravenously every 3 weeks. Patients received a maximum of 6 chemotherapy cycles, after which patients received weekly cetuximab with either placebo or motolimod every 4 weeks. Main Outcomes and Measures Progression-free survival (PFS) as determined by independent central review using immune-related RECIST (Response Evaluation Criteria in Solid Tumors). Key secondary end points included overall survival (OS) and safety. Results Of 195 patients enrolled, 85% were men (n = 166); 82% were white (n = 159); median age was 58 years (range 23-81 years). Median PFS was 6.1 vs 5.9 months (hazard ratio [HR], 0.99; 1-sided 90% CI, 0.00-1.22; P = .47), and median OS was 13.5 vs 11.3 months (HR, 0.95; 1-sided 90% CI, 0.00-1.22; P = .40) for motolimod vs placebo. Increased incidence of injection site reactions, pyrexia, chills, anemia, and acneiform rash were noted with motolimod. Of 83 cases oropharyngeal cancer, 52 (63%) were human papillomavirus (HPV) positive. In a prespecified subgroup analysis of HPV-positive participants, motolimod vs placebo resulted in significantly longer PFS (7.8 vs 5.9 months; HR, 0.58; 1-sided 90% CI, 0.00-0.90; P = .046) and OS (15.2 vs 12.6 months; HR, 0.41; 1-sided 90% CI, 0.00-0.77; P = .03). In an exploratory analysis, patients with injection site reactions had longer PFS and OS (median PFS, 7.1 vs 5.9 months; HR, 0.69; 1-sided 90% CI, 0.00-0.93; P = .06; and median OS, 18.7 vs 12.6; HR, 0.56; 1-sided 90% CI, 0.00-0.81; P = .02). Conclusions and Relevance Adding motolimod to the EXTREME regimen was well tolerated but did not improve PFS or OS in the intent-to-treat population. Significant benefit was observed in HPV-positive patients and those with injection site reactions, suggesting that TLR8 stimulation may benefit subset- and biomarker-selected patients. Trial Registration ClinicalTrials.gov identifier: NCT01836029.

Patient Characteristics and Costs in Recurrent or Refractory Head and Neck Cancer: Retrospective Analysis of a Community Oncology Database

PURPOSE The goal of this study was to describe patient characteristics, health resource utilization (HRU), and costs associated with treating recurrent or refractory head and neck cancer (HNC) among patients with disease progression in the community oncology setting. METHODS This retrospective observational study was conducted by using data from the Vector Oncology Data Warehouse. Patients had been diagnosed with locally advanced or metastatic (stage III-IVc) HNC between January 1, 2007, and October 1, 2015. Patients also had evidence of at least 1 systemic anticancer therapy regimen following the diagnosis of advanced HNC, with at least 1 disease progression. Costs, treatment patterns, and HRU were evaluated beginning with diagnosis of advanced HNC through 3 lines of therapy. Costs of surgery or radiation were not available for inclusion in the analysis. Total cost for the study period and cost per month were analyzed by using a generalized linear regression model. FINDINGS The study included 462 patients (median age, 61 years; range, 26-99 years); of these, 81% were male, 77% were white, and 21% were black. At initial diagnosis, the most frequent tumor locations were the hypopharynx/larynx (31%) and the oropharynx (31%). Human papilloma virus testing was most frequent among the oropharynx group (22% tested, 52% positive). Overall, 42% were current tobacco users and 22% were current or past alcohol abusers/excessive users. Platinum-based combination therapies were the most frequently administered chemotherapy in both first (42%) and second (40%) lines of treatment. Through the overall study period (mean, 20.5 months), 74% of patients were hospitalized, 19% had an emergency department visit, and 100% had an office visit. The overall mean (SD) duration of hospital stay was 12.6 days, and the median number of office visits per patient was 35. The mean monthly health care cost for the overall study period was

Treatment Patterns and Outcomes in Stage IV Bladder Cancer in a Community Oncology Setting: 2008-2015

14,391 (95% CI, 12,739-16,044). Hospitalization costs represented ~57% of the total expenditures. Statistically significant predictors of higher overall cost included primary tumor location in the oral cavity, history of alcohol abuse/excess use, use of cetuximab, and higher comorbidity index. Older age and being stage IV versus other stages of disease at diagnosis were associated with lower overall cost. IMPLICATIONS These data suggest that costs of care in patients with recurrent or refractory HNC are related to patient characteristics and treatment patterns. Identification of factors contributing to the costs of care in HNC may provide a useful foundation for developing strategies to control rising costs.

The effect of adjuvant radiation on survival for patients with resected localized or regional primary small cell carcinoma of the breast.

Introduction: Current real‐world data regarding treatment patterns in advanced bladder cancer in the community setting are limited. This study describes patient characteristics, treatment patterns, and effectiveness outcomes for stage IV bladder cancer in the community setting. Methods: Medical records data of adults diagnosed with stage IV bladder cancer between January 1, 2008 and June 1, 2015 were retrospectively collected from a network of United States community oncology practices. Patient characteristics, treatment patterns, and efficacy outcomes were assessed. Across‐group comparisons were conducted using bivariate analyses. Kaplan‐Meier and Cox regression analyses of progression‐free survival and overall survival (OS) were conducted. Results: Of 508 patients (mean age, 70 ± 11 years), 75.2% were male, 79.1% white, 15.4% black, and 71.5% were ≥ 65 years. The most prevalent comorbidities were diabetes (23.4%) and renal disease (16.5%). Overall, 56% of patients received first‐line platinum‐based chemotherapy; the most common regimen was gemcitabine/carboplatin (23.6%), followed by gemcitabine/cisplatin (17%). The median OS was 9.4 months from stage IV bladder cancer diagnosis and 8.4 months from start of first‐line therapy. Cox regression analysis of OS from diagnosis showed a higher risk of death for patients with no treatment (hazard ratio [HR], 2.06; P < .0001) or other treatment (HR, 1.83; P = .002) versus cisplatin and for patients with impaired performance (HR, 2.05; P < .0001). Conclusion: Platinum‐based chemotherapy was the most prescribed treatment for stage IV bladder cancer in the community setting. Several patients were not treated with any chemotherapy, although we did not observe the reason for no treatment. This study highlights an unmet need in this population, particularly in a relapsed/refractory setting, and the need for improvement in outcomes.

Colon Cancer, Version 3.2014

87 Background: Primary small cell carcinoma of the breast (SCCB) is rare and prognosis, the role of radiation therapy and outcomes are largely undefined. METHODS Using case listing session of SEER 18 (1973-2010) we examined outcomes for patients (pts) with SCCB. Analyses were conducted with SEER*Stat 8.1.2, Microsoft Excel 2007 and GraphPad Prism 6. Comparisons were made using the chi-squared test and log rank test (Mantel-Cox); all p-values were 2-sided. RESULTS 199 pts with primary SCCB with staging were identified; median age was 65 (range 28-97); 98% were female. 84 (42%) had localized disease (dz), 77 (39%) had regional dz and 38 (19%) had distant dz. 95% of pts with localized dz and 88% of pts with regional dz had breast surgery. Median overall survival (OS) varied by stage (150 months [m] v 56m v 7m, p<0.001) and radiation did not impact OS for pts with either localized (202m v 147m, p=0.477) or regional (52m v 75m, p=0.650) dz. For comparison 81,933 cases of small cell lung cancer (SCLC) were identified in SEER; 8% localized, 29%regional and 63% distant disease. Outcomes were superior for pts with SCCB with localized (150m v 16m, p<0.001) and regional dz (56m v 13m, p<0.001) but not distant dz (7m v 7m, p=0.043). CONCLUSIONS SCCB presents at an earlier stage than and has a more favorable prognosis by stage for localized and regional dz than SCLC. Adjuvant radiation does not improve survival for patients with localized or regional SCCB.