Expert says Nivolumab Poised to Change Standard of Care in SCCHN

Source: www.onclive.com Author: Laura Panjwani Nivolumab (Opdivo) is a game-changing agent for the treatment of patients with squamous cell carcinoma of the head and neck (SCCHN), according to Robert L. Ferris, MD, PhD. “Recent findings have shown us that this agent is really the new standard-of-care option for all platinum-refractory patients with head and neck cancer,” says Ferris, vice chair for Clinical Operations, associate director for Translational Research, and co-leader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute. “This is regardless of whether patients are PD-L1–positive or negative or whether they are HPV-positive or negative.” The PD-L1 inhibitor received a priority review designation by the FDA in July 2016 based on the CheckMate-141 study, which demonstrated a median overall survival (OS) with nivolumab of 7.5 months compared with 5.1 months with investigator's choice of therapy (HR, 0.70; 95% CI, 0.51-0.96; P = .0101) in patients with recurrent or metastatic SCCHN. The objective response rate (ORR) was 13.3% with nivolumab and 5.8% for investigator's choice. The FDA is scheduled to make a decision on the application for the PD-1 inhibitor by November 11, 2016, as part of the Prescription Drug User Fee Act. Ferris was the lead author on an analysis that further evaluated preliminary data from CheckMate-141, which was presented at the 2016 ASCO Annual Meeting. In an interview with OncLive, he discusses the findings of this study, potential biomarkers for nivolumab, and questions that remain regarding the use of the immunotherapy in SCCHN. OncLive: What [...]

2016-08-24T13:28:58-07:00August, 2016|Oral Cancer News|

Integrative and Comparative Genomic Analysis of HPV-Positive and HPV-Negative Head and Neck Squamous Cell Carcinomas

Source: http://clincancerres.aacrjournals.org/Authors: Tanguy Y. Seiwert, Zhixiang Zuo, Michaela K. Keck, Arun Khattri, Chandra S. Pedamallu, Thomas Stricker, Christopher Brown, Trevor J. Pugh, Petar Stojanov, Juok Cho, Michael S. Lawrence, Gad Getz, Johannes Brägelmann, Rebecca DeBoer, Ralph R. Weichselbau, Alexander Langerman, Louis Portugal, Elizabeth Blair, Kerstin Stenson, Mark W. Lingen, Ezra E.W. Cohen, Everett E. Vokes, Kevin P. White, and Peter S. Hammerman  Abstract Purpose: The genetic differences between human papilloma virus (HPV)–positive and –negative head and neck squamous cell carcinomas (HNSCC) remain largely unknown. To identify differential biology and novel therapeutic targets for both entities, we determined mutations and copy-number aberrations in a large cohort of locoregionally advanced HNSCC. Experimental Design: We performed massively parallel sequencing of 617 cancer-associated genes in 120 matched tumor/normal samples (42.5% HPV-positive). Mutations and copy-number aberrations were determined and results validated with a secondary method. Results: The overall mutational burden in HPV-negative and HPV-positive HNSCC was similar with an average of 15.2 versus 14.4 somatic exonic mutations in the targeted cancer-associated genes. HPV-negative tumors showed a mutational spectrum concordant with published lung squamous cell carcinoma analyses with enrichment for mutations in TP53, CDKN2A, MLL2, CUL3, NSD1, PIK3CA, and NOTCH genes. HPV-positive tumors showed unique mutations in DDX3X, FGFR2/3 and aberrations in PIK3CA, KRAS, MLL2/3, and NOTCH1 were enriched in HPV-positive tumors. Currently targetable genomic alterations were identified in FGFR1, DDR2, EGFR, FGFR2/3, EPHA2, and PIK3CA. EGFR, CCND1, and FGFR1 amplifications occurred in HPV-negative tumors, whereas 17.6% of HPV-positive tumors harbored mutations in fibroblast growth factor receptor [...]

2015-02-05T14:34:06-07:00February, 2015|Oral Cancer News|

Five genetic subgroups revealed in head and neck tumor analysis

Source: www.onclive.com Author: Ben Leach Oncologists who treat patients with head and neck cancer are aware that those whose disease has been caused by human papillomavirus (HPV) have significantly better outcomes than those whose disease is caused by other factors such as smoking. However, new research suggests that there may be five distinct subgroups in which specific genetic profiles may be utilized to guide treatment decisions in patients. “Currently, we treat all patients with head and neck cancer in essentially the same way,” said Ezra E. W. Cohen, MD, co-director of the Head and Neck Cancer Program at the University of Chicago Medical Center. “But we do know that the prognosis for patients who are HPV-positive is much better.” To determine whether patients’ genetic profiles differed, Cohen and his colleagues at the University of Chicago, led by researcher Tanguy Seiwert, MD, took approximately 130 tumor samples from patients with stage IV squamous cell carcinoma of the head and neck and performed gene expression (mRNA) analysis. The samples were gathered before patients received therapy, and all of the participants subsequently were treated with a 5-fluorouracil, hydroxyurea, and concurrent radiation (FHX)-based regimen. This way, the researchers could determine the outcome as a function of gene expression in the groups identified through the analysis, since patients received the same treatment across all the subgroups eventually identified. Cohen said that patients were enrolled regardless of whether they were HPV-positive or HPV-negative. Based on these findings, the University of Chicago team was able to classify [...]

HPV infection may be linked to poor head and neck cancer survival rates in African Americans

Source: www.aacr.org Author: staff American Association for Cancer Research Hosts Press Conference on New Study A groundbreaking study in Cancer Prevention Research, a journal of the American Association for Cancer Research, suggests that having the human papillomavirus (HPV) improves survival in squamous cell carcinoma of the head and neck. Furthermore, African Americans had far less HPV infection than whites, which led to worse survival. "There is currently no consensus on why blacks fare worse with squamous cell carcinoma of the head and neck than whites, but this is the first clue that it may be biologic rather than related to issues of access, insurance or provider attitudes," said senior author Kevin Cullen, M.D., director of the University of Maryland Marlene and Stewart Greenebaum Cancer Center and professor of medicine at the University of Maryland School of Medicine. Cullen's research showed that median overall survival was more than threefold higher for whites (70.6 months) than for African Americans (20.9 months) who were treated with chemotherapy and radiation. When the researchers examined patients by HPV status, they found that HPV-negative patients had a median survival of 26.6 months, while the survival rate for HPV-positive patients could not be calculated because most were still alive. Overall, 4 percent of African American patients and 34 percent of white patients were HPV positive. Cullen said the survival difference was entirely due to HPV status, as survival rates were similar among HPV-negative patients. Scott Lippman, M.D., chair of the Department of Clinical Cancer Prevention at the [...]

Go to Top