cetuximab

Treatment paradigms are shifting for locally advanced HPV-positive head and neck cancers

Source: www.onclive.com Authors: Kaveh Zakeri, MD, MAS, Nancy Y. Lee, MD The standard of care for patients with locally advanced head and neck squamous cell carcinomas does not substantially differ according to human papillomavirus (HPV) status in the National Comprehensive Cancer Network guidelines.1 Resectable tumors can be treated with surgery followed by adjuvant therapy. Alternatively, definitive chemoradiation therapy with cisplatin is the other dominant treatment paradigm. Incidence of HPV-associated oropharyngeal squamous cell carcinoma has increased rapidly and is associated with higher overall survival (OS) compared with cancers caused by smoking and alcohol.2,3 Given the unique biology of HPV-associated oropharyngeal disease, a separate staging system was developed for these tumors.4 HPV-associated oropharyngeal cancers are more radiosensitive and chemosensitive than cancers caused by smoking and alcohol, yet the traditional treatment paradigms—including high doses of radiation and chemotherapy—were developed prior to the epidemic of HPV-associated disease. De-escalation of therapy has been proposed for HPV-associated oropharyngeal cancer based on data demonstrating high OS and progression-free survival (PFS).5 De-escalation of therapy has been investigated for both definitive surgical and chemoradiation therapy paradigms. Most de-escalated approaches focus on selecting patients according to clinical features, such as disease stage and smoking status, whereas personalized de-escalation reduces treatment intensity for patients according to treatment response. Transoral Robotic Surgery Followed by Adjuvant Radiotherapy Transoral robotic surgery (TORS) is a minimally invasive approach that reduces morbidity compared with traditional, open surgery for patients with oropharyngeal cancers. TORS is a standard of care option for patients with resectable tonsil or base [...]

Oral Cancer Foundation News Team - A2021-11-23T08:16:08-07:00November, 2021|Oral Cancer News|

Calls grow for treatment deintensification of HPV-positive OPC

Source: ww.pharmacytimes.com Author: Bryan Fitzgerald, PharmD, BCOP Health-System Edition, July 2021, Volume 10, Issue 4 Oropharyngeal cancer (OPC) is a type of head and neck cancer that affects structures in the back of the throat, including the base of the tongue, the posterior pharynx, the soft palate, and the tonsils.1 In the United States, rates of OPC are increasing each year, with an estimated 54,010 new cases in 2021.2 Well-established risk factors include alcohol abuse; exposure to tobacco, including chewing tobacco, cigarettes, and pipes; and infection with human papillomavirus (HPV). With an estimated 43 million infections in 2018, HPV is the most common sexually transmitted infection in the United States.3 HPV infection is causally linked with cancers of the anogenital region, including anal, cervical, penile, vaginal, and vulvar cancers. When HPV is spread orally, infections can also lead to the development of OPC. In the United States, more than 70% of OPC cases are caused by HPV.4 HPV is a group of more than 100 viruses, including certain high-risk strains associated with the development of cancer. The HPV-16 strain is responsible for causing the majority of HPV-positive (HPV+) OPC cases, with HPV-18, HPV-33, and HPV-35 also contributing, albeit significantly less than HPV-16.1 In these high-risk HPV strains, the viral genome encodes several oncogenic proteins that inhibit tumor suppressor proteins, leading to chromosomal instability and malignancy in infected cells. HPV+ OPC is considered a genetically distinct form of OPC. Compared with HPV-negative (HPC–) OPC cases, HPV+ OPC is associated with a [...]

Oral Cancer Foundation News Team - A2021-07-21T10:05:34-07:00July, 2021|Oral Cancer News|

On treating advanced head and neck cancer without cisplatin – an oncology grand rounds discussion

Source: www.medpagetoday.com Author: Mark L. Fuerst An oncology grand rounds discussion with Sachin Jhawar, MD. Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous set of diseases with different features and treatment recommendations. Physicians face challenges in initial treatment decision-making and response assessments, including the changing role of surgery, the incorporation of human papilloma and Epstein Barr virus status, as well as the potential for treatment de-escalation using patient-related and tumor-related factors. A recent "Oncology Grand Rounds" article in the Journal of Clinical Oncology provides an overview of treating advanced HNSCC when cisplatin is not an option, including concurrent chemotherapy, cetuximab, targeted therapy, and immunotherapy. In the following interview, the paper's lead author, Sachin Jhawar, MD, of Ohio State University Comprehensive Cancer Center in Columbus, reviews the main issues. What is the focus of the article? Jhawar: We focused on patients with locally advanced disease who would be receiving definitive non-surgical treatment when possible treatment with concurrent cisplatin, delivered either every 3 weeks or weekly, is always the preferred treatment. We specifically wanted to delve into the subset of patients who we would not recommend to receive cisplatin because of age or comorbidities. This could be concurrent chemotherapy (carboplatin/paclitaxel), concurrent cetuximab, and altered or standard fractionation radiation schedules without systemic therapy, as well as when to consider immunotherapy and palliative radiation for those with recurrent or metastatic disease. There is also a great deal of institutional preference involved. At our institution, we prefer concurrent carboplatin/paclitaxel in patients who cannot [...]

Oral Cancer Foundation News Team - A2021-03-19T09:09:44-07:00March, 2021|Oral Cancer News|

FDA grants fast track designation to NBTXR3 in locally advanced head and neck cancers

Source: www.targetedonc.com Author: Nichole Tucker An FDA Fast Track Designation was granted to the first-in-class radioenhancer NBTXR3 with or without cetuximab (Erbitux) for the treatment of patients with locally advanced head and neck squamous cell cancer who are not eligible for platinum-based chemotherapy, according to a press release from Nanobiotix.1 NBTXR3 showed preliminary signals of antitumor activity in this patient population in a phase I study of 12 patients with advanced-stage head and neck squamous cell carcinoma (HNSCC). Specifically, 10 of the 11 evaluable patients had a complete response (CR) or a partial response to treatment, which included 2 CRs at dose levels ≤10% and 5 CRs at dose levels >10%.2 Treatment with NBTXR3 was also found to be safe and tolerable in patients with HNSCC. There were no serious adverse events or dose-limiting toxicities (DLTs) observed, which allowed patients to continue with their treatment as planned. The adverse events found to be related to injection with NBTXR3 included grade 1/2 injection pain and tumor hemorrhage. Patients in the study received either a single intratumor injection or single-arterial injection of NBTXR3 on day 1 followed by intensity-modulated radiation therapy 2 hours later, which lasted for up to 7 weeks. Radiotherapy was continued in all patients unless their tumor did not shrink by 50% of the baseline size. Those patients who did achieve the tumor shrinkage goals then received salvage tumor surgery. The primary end point of the study was the determination of the recommended dose of the drug and early [...]

Oral Cancer Foundation News Team - A2020-02-11T08:31:16-07:00February, 2020|Oral Cancer News|

Palbociclib plus cetuximab shows antitumor activity among head and neck cancer subset

Source: www.healio.com Author: Adkins D, et al. A combination of palbociclib and cetuximab demonstrated substantial antitumor activity among patients with platinum- or cetuximab-resistant HPV-unrelated head and neck squamous cell carcinoma, according to results of a multigroup phase 2 trial published in The Lancet Oncology. “Currently, effective therapeutic options for patients with cetuximab-resistant HNSCC are few. Traditional chemotherapy has marginal activity, with 6% of patients or fewer achieving a tumor response,” Douglas R. Adkins, MD, professor in the oncology division of the department of medicine at Washington University School of Medicine in St. Louis, and colleagues wrote. “The most effective therapy for these patients might be pembrolizumab [Keytruda, Merck] or nivolumab [Opdivo, Bristol-Myers Squibb], which have resulted in responses in 11% to 16% of patients and median OS of 6.9 months to 8 months. Novel treatment strategies are needed for patients with recurrent or metastatic HNSCC.” The combination of the cyclin-dependent kinase (CDK) 4/6 inhibitor palbociclib (Ibrance, Pfizer) and epidermal growth factor receptor inhibitor cetuximab (Erbitux, Eli Lilly) appeared safe and tolerable in the phase 1 portion of the multicenter trial, conducted across eight U.S. university sites. For phase 2, Adkins and colleagues divided 62 patients with HPV-unrelated HNSCC (median age, 66 years; interquartile range [IQR], 58-70; 71% men) into two groups: those who were platinum-resistant (group 1; n = 30) and those who were resistant to cetuximab (group 2; n = 32). Primary tumor sites included the oral cavity (42%) and larynx (29%), and 81% of patients had received one [...]

Oral Cancer Foundation News Team - A2019-08-21T17:26:46-07:00August, 2019|Oral Cancer News|

No De-escalation of Therapy for HPV+ Throat Cancer

Source: www.medscape.com Author: Alexander M. Castellino, PhD Another trial has shown that de-escalating therapy does not work in patients with good prognosis human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma or throat cancers. Results from the De-ESCALaTE HPV study show that using the targeted drug cetuximab with radiotherapy does not improve side effects and, more importantly, has worse survival compared with the standard of care — chemotherapy with cisplatin and radiotherapy. The finding echoes the results from the US National Cancer Institute's Radiation Therapy Oncology Group (RTOG) 1016 trial, the top-line results of which were released earlier this year, and details of which were presented this week at the American Society of Radiation Oncology (ASTRO) 2018 meeting. "Do not change your clinical practice of using cisplatin with radiotherapy in these patients," cautioned Hisham Mehanna, MBChB, PhD, chair of head and neck surgery at the University of Birmingham, United Kingdom, and lead investigator of the De-ESCALaTe study. He presented the results during a presidential session here at the European Society for Medical Oncology (ESMO) 2018 Congress (abstract LBA9). "Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise — we thought it would lead to the same survival rates but better toxicity. Patients with throat cancer who are HPV+ should be given cisplatin, and not cetuximab, where possible," Mehanna said in a statement. Hope for Fewer Side Effects Cetuximab with radiation is already approved by the US Food and Drug [...]

Charlotte Parker2018-10-28T11:45:33-07:00October, 2018|OCF In The News, Oral Cancer News|

Patients with HPV-positive oropharynx cancer should receive chemoradiation

Source: medicalxpress.com Author: provided by European Society for Medical Oncology Patients with human papilloma virus (HPV)-positive throat cancer should receive chemoradiotherapy rather than cetuximab with radiotherapy, according to late-breaking research reported at the ESMO 2018 Congress in Munich. "Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects but there has been no head-to-head comparison of the two treatments," said study author Prof Hisham Mehanna, Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham, UK. Throat cancer is rapidly becoming more common in Western countries. For example in the UK, incidence was unchanged in 1970 to 1995, then doubled in 1996 to 2006, and doubled again in 2006 to 2010.The rise has been attributed to HPV, a sexually transmitted infection. Most throat cancer was previously caused by smoking and alcohol and affected 65-70 year-old working class men. Today HPV is the main cause and patients are around 55, middle class, working, and have young children. HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30-40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy, for example because of poor kidney function or older age, receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy. This study compared side effects and survival with the two treatments in [...]

Oral Cancer Foundation News Team - A2018-10-23T12:14:09-07:00October, 2018|Oral Cancer News|

HPV16 vaccine yields added benefit in recurrent throat cancer

Source: www.medpagetoday.com Author: Ian Ingram, Deputy Managing Editor, MedPage Today Adding a tumor-specific vaccine to PD-1 checkpoint inhibition was safe and effective in HPV16-positive patients with recurrent or metastatic oropharyngeal cancer, a small phase II trial found. Among 24 patients treated with nivolumab (Opdivo) and the ISA101 long peptide vaccine, 22 of whom had oropharyngeal cancer, 33% responded and median overall survival was 17.5 months, Cornelis Melief, PhD, of ISA Pharmaceuticals in the Netherlands, reported here at the 4th annual Cancer Immunotherapy Conference. All eight of the responders had oropharyngeal cancer (36%), with two complete and six partial responses. The median duration of response among these patients was 10.3 months, and responses were seen in both platin- and cetuximab-refractory patients, and those refractory to both. Melief noted that one of the partial responders had total clearance of the primary tumor, but a solitary lung metastasis remained, but was stable at 2.5 years. Rate of overall survival at 6 and 12 months was 75% and 70%, respectively. The combination was well tolerated and safe, said Melief, with no increase in the rate of serious adverse events. A randomized trial is planned to confirm the findings. "The results of our trial are among the first clinical data to support the general concept of combining cancer vaccination with immune checkpoint blockade to enhance efficacy of vaccine-activated T cells in the immunosuppressive tumor environment," Melief's group wrote in JAMA Oncology, where the findings were also published. The findings compare favorably to outcomes in a [...]

Oral Cancer Foundation News Team - A2018-10-04T09:03:12-07:00October, 2018|Oral Cancer News|

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 [...]

Charlotte Parker2016-08-24T13:28:58-07:00August, 2016|Oral Cancer News|

Nivolumab Improved Survival For Patients With Head and Neck Squamous Cell Carcinoma

Source: www.aacr.orgAuthor: AACR Newsroom Staff NEW ORLEANS — Treatment with the immunotherapeutic nivolumab (Opdivo) improved survival for patients with recurrent or metastatic head and neck squamous cell carcinoma that progressed after platinum-based chemotherapy compared with single-agent chemotherapy of the investigator’s choice, according to results from the CheckMate-141 phase III clinical trial presented here at the AACR Annual Meeting 2016, April 16-20. “Recurrent or metastatic head and neck squamous cell carcinoma that is not responsive to platinum-based chemotherapy progresses very rapidly, and patients have a very poor prognosis,” said Maura L. Gillison, MD, PhD, a professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. “Treatment usually involves single-agent chemotherapy. However, no therapy has been shown to improve survival for this patient population. New treatment options are desperately needed. “This study is the first randomized clinical trial to clearly demonstrate improved overall survival for patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma,” continued Gillison. “We hope that the results will establish nivolumab as a new standard of care option for this patient population and thereby fulfill a huge unmet need.” CheckMate-141 was a randomized, phase III clinical trial designed to determine whether the PD-1 inhibitor nivolumab could extend overall survival for patients with platinum-refractory recurrent or metastatic head and neck squamous cell carcinoma compared with treatment of the investigator’s choice, which was any of the commonly used therapeutics docetaxel, methotrexate, or [...]

Charlotte Parker2016-04-19T10:49:39-07:00April, 2016|OCF In The News, Oral Cancer News|