A randomized phase II study of cetuximab every 2 weeks at either 500 or 750 mg/m2 for patients with recurrent or metastatic head and neck squamous cell cancer.

Cetuximab is typically administered on a weekly schedule for patients with recurrent or metastatic head and neck squamous cell cancer (HNSCC). This study explores cetuximab administered every 2 weeks (q2w). In this multicenter randomized prospective phase II study, eligible patients (≤2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease; ECOG performance status ≤2) were randomized to receive cetuximab q2w at 500 mg/m(2) (Group A) or 750 mg/m(2) (Group B). The primary end point was response rate (RECIST 1.0). Sixty-one patients were enrolled: 35 in Group A and 26 in Group B, which was closed early for lack of efficacy. Confirmed partial response rates were 11% for Group A (4/35) and 8% for Group B (2/26) according to intention to treat analysis. Partial responses occurred only among patients whose primary tumors were in the oral cavity or larynx. Median progression-free survival (PFS) and median overall survival (OS) were similar for both groups (PFS, 2.2 and 2.0 months; OS, 7.0 and 9.4 months; Groups A and B, respectively). The most common cetuximab-related adverse events (all grades) among treated subjects included rash, fatigue, and hypomagnesemia. Cetuximab, 500 mg/m(2), q2w achieves similar efficacy as conventional dosing for patients with recurrent or metastatic HNSCC. Escalating the dose to 750 mg/m(2) q2w offers no obvious therapeutic advantage.

Employment and return to work following chemoradiation in patient with HPV-related oropharyngeal cancer.

BACKGROUND: Human papillomavirus (HPV)-positive oropharyngeal cancer primarily affects working-age adults. Chemotherapy and radiation (CTRT) used to treat this disease may adversely impact a survivors' ability to work after treatment. METHODS: We surveyed participants with HPV-positive oropharyngeal cancer who completed CTRT regarding employment. We examined the associations between 1) sociodemographic and clinical factors and employment outcomes, and 2) health-related quality of life and satisfaction with ability to work. RESULTS: 102 participants were employed full-time at diagnosis for pay and surveyed at a median of 23 months post-CTRT (range 12-57 months). The median age at diagnosis was 57 years (range 25-76 years). During CTRT, 8 % stopped working permanently, 89 % took time off or reduced responsibility but later returned, and 3 % reported no change. For those who took time off but returned, median time to return to work was 14.5 weeks. In multivariable analysis, younger age predicted for needing more than the median time off. At time of survey, 85 % participants were working, 7 % had retired, and 8 % were not working for other reasons. Seventeen percent of participants were not satisfied with their current ability to work, which was associated with poorer health-related quality of life and persistent treatment toxicities (p < 0.001). CONCLUSIONS: CTRT interrupts employment in the majority of working patients with HPV-positive oropharyngeal cancer but most return. However, treatment-related toxicities might lead to dissatisfaction with ability to work.

Phase II trial of bevacizumab + cetuximab + cisplatin with concurrent intensity-modulated radiation therapy for patients with stage III/IVB head and neck squamous cell carcinoma.

BACKGROUND: The purpose of this study was to evaluate the efficacy and tolerability of the addition of 2 monoclonal antibodies, bevacizumab and cetuximab, to 2 cycles of high-dose cisplatin administered concurrently with intensity-modulated radiation therapy (IMRT) for head and neck squamous cell carcinoma (HNSCC). METHODS: Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m(2) loading dose, followed by 250 mg/m(2) weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m(2) , days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. RESULTS: Among 30 patients enrolled in this study, the primary tumor site was the oropharynx in 24 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharyngeal tumors). Median age was 57 years (range, 38-77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow-up of 33.8 months, 2-year PFS was 88.5% (95% confidence interval [CI] = 68.1-96.1) and 2-year OS was 92.8% (95% CI = 74.2-98.1). CONCLUSION: The addition of bevacizumab and cetuximab to 2 cycles of cisplatin, given concurrently with IMRT, was well-tolerated and was associated with favorable efficacy outcomes in this patient population. © 2015 Wiley Periodicals, Inc. Head Neck 38: E566-E570, 2016.

Phase II Study of a Non-Platinum-Containing Doublet of Paclitaxel and Pemetrexed with Bevacizumab as Initial Therapy for Patients with Advanced Lung Adenocarcinomas.

INTRODUCTION: Many patients with lung cancers cannot receive platinum-containing regimens owing to comorbid medical conditions. We designed the PPB (paclitaxel, pemetrexed, and bevacizumab) regimen to maintain or improve outcomes while averting the unique toxicities of platinum-based chemotherapies. METHODS: We enrolled patients with untreated, advanced lung adenocarcinomas with measurable disease and no contraindications to bevacizumab. Participants received paclitaxel, 90 mg/m(2), pemetrexed, 500 mg/m(2), and bevacizumab, 10 mg/kg, every 14 days for 6 months and continued to receive pemetrexed and bevacizumab every 14 days until progression or unacceptable toxicity. RESULTS: Of the 44 patients treated, 50% were women; the median age was 61 years and 89% had a Karnofsky performance status of at least 80%. We genotyped 38 patients with the following results: Kirsten rat sarcoma viral oncogene homolog gene (KRAS), 16; anaplastic lymphoma receptor tyrosine kinase gene (ALK), three; B-Raf proto-oncogene, serine/threonine kinase gene (BRAF) V600E, two; erb-b2 receptor tyrosine kinase 2 gene (HER2)/phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), one; epidermal growth factor receptor gene (EGFR) exon 20 insertion, one; and driver 15, none. A total of 23 patients achieved a PR (52%, 95% confidence interval: 37-68), including seven of 16 with KRAS-mutant tumors. The overall survival rate at 2 years was 43% with a median of 17 months (95% confidence interval: 10-29). Grade 3/4 treatment-related toxicities included elevated alanine transaminase level (16%), fatigue (16%), leukopenia (9%), anemia (7%), elevated aspartate transaminase level (7%), edema (5%), and pleural effusions (5%). Two patients died of respiratory failure without disease progression. CONCLUSIONS: The PPB regimen produced a high response rate in patients with lung adenocarcinomas regardless of mutational status. Survival and toxicities were comparable to those in the phase II reports testing platinum-containing doublets with bevacizumab. These results justify use of the PPB regimen in fit patients in whom three-drug regimens including bevacizumab are appropriate.

Large Cell Neuroendocrine Carcinoma of the Lung: Clinico-Pathologic Features, Treatment, and Outcomes.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) accounts for approximately 3% of lung cancers. Pathologic classification and optimal therapies are debated. We report the clinicopathologic features, treatment and survival of a series of patients with stage IV LCNEC. MATERIALS AND METHODS: Cases of pathologically-confirmed stage IV LCNEC evaluated at Memorial Sloan Kettering Cancer Center from 2006 to 2013 were identified. We collected demographic, treatment, and survival data. Available radiology was evaluated by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. RESULTS: Forty-nine patients with stage IV LCNEC were identified. The median age was 64 years, 63% of patients were male, and 88% were smokers. Twenty-three patients (n = 23/49; 47%) had brain metastases, 17 at diagnosis and 6 during the disease course. Seventeen LCNEC patients (35%) had molecular testing, of which 24% had KRAS mutations (n = 4/17). Treatment data for first-line metastatic disease was available on 37 patients: 70% (n = 26) received platinum/etoposide and 30% (n = 11) received other regimens. RECIST was completed on 23 patients with available imaging; objective response rate was 37% (95% confidence interval, 16%-62%) with platinum/etoposide, while those treated with other first-line regimens did not achieve a response. Median overall survival was 10.2 months (95% confidence interval, 8.6-16.4 months) for the entire cohort. CONCLUSION: Patients with stage IV LCNEC have a high incidence of brain metastases. KRAS mutations are common. Patients with stage IV LCNEC do not respond as well to platinum/etoposide compared with historic data for extensive stage small-cell lung cancer; however, the prognosis is similar. Prospective studies are needed to define optimum therapy for stage IV LCNEC.