Research Leader Discusses FDA-Funded Immunotherapy for Head and Neck Cancer

 Source: www.onclive.comAuthor: Gina Columbus  Brett Miles, MD, DDS   The investigational immunotherapy axalimogene filolisbac (ADXS11-001) has emerged as a potentially practice-changing agent in the treatment of HPV-related oropharyngeal cancer. Shown to generate T cells directed against a cancer antigen and neutralize suppressor regulatory T cells and myeloid-derived suppressor cells that protect the tumor microenvironment from an immunologic attack and contribute to tumor growth, ADXS11-001 is the first of its kind—a therapeutic vaccine for the disease. The agent is being examined in an ongoing phase II trial, which was reported as one of 18 recipients of research grants recently awarded by the FDA’s Office of Orphan Product Development. The grants, given to sites for product development in rare diseases, total more than $19 million. The ADXS11-001 grant provides collaborating researchers from Baylor College of Medicine and the Icahn School of Medicine at Mount Sinai with more than $1.1 million over 3 years. Eligible patients for the phase II study are newly diagnosed with stage II to IV HPV16-positive oropharynx squamous cell carcinoma who are scheduled to receive ablative transoral robotic surgery. In an interview with OncLive, the study’s surgical principal investigator, Brett Miles, MD, DDS, associate professor of Otolaryngology Head and Neck Surgery, co-chief, Division of Head and Neck Oncology, Icahn School of Medicine at Mount Sinai, discusses the potential of ADXS11-001 in HPV-associated head and neck cancer and other emerging therapies and treatment strategies. OncLive: Congratulations on your study being awarded a research grant from the FDA. How does it [...]

2015-09-29T11:26:02-07:00September, 2015|Oral Cancer News|

Researchers propose new staging model for HPV+ oropharyngeal cancer

Source: www.drbicuspid.com Author: Donna Domino Researchers are proposing a new tumor-staging model for predicting the outcomes and guiding treatments for patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC), according to a new study in the Journal of Clinical Oncology. Since HPV-related cancer differs significantly from smoking-related cancer, less intensive treatment strategies may be more appropriate, the study authors concluded. Treatment regimens for oropharyngeal cancer have intensified over time and carry a toxicity burden, the Canadian researchers noted. In the last few years, research has found that oropharyngeal cancer caused by HPV behaves differently than OPC caused by smoking and alcohol, yet both cancers use the same tumor classification model. Therefore, regardless of whether the OPC was caused by HPV or smoking, the treatment and perceived prognosis based on tumor staging has remained the same, even though patient outcomes vary considerably, the study authors noted (Journal of Clinical Oncology, February 10, 2015, Vol. 31:5, pp. 543-550). A new tumor-staging model will help separate patients with promising prognoses from those with negative ones to design the most appropriate treatment strategies for each group, according to the researchers from Toronto's Princess Margaret Cancer Centre. The researchers analyzed 899 oropharyngeal cancer patients, including 505 (56%) patients with HPV who had been treated with radiotherapy or chemoradiotherapy from 2001 to 2009. The HPV-positive patients (382) had higher recurrence-free survival rates after about four years compared with HPV-negative patients (123). Disease recurrence was 16.7% (64) among HPV-positive patients; 38.2% among HPV-negative patients (47). The tumor staging [...]

2015-02-25T08:55:13-07:00February, 2015|Oral Cancer News|

Docetaxel regimen tops cisplatin in head and neck cancer

Source: www.cancernetwork.com Author: Anna Azvolinsky, PhD A phase II study has demonstrated that combining docetaxel-based chemoradiotherapy and the antibody cetuximab postoperatively in patients with high-risk squamous cell carcinoma of the head and neck led to improved disease-free and overall survival, with no unexpected toxicities. The results of the study were published in the Journal of Clinical Oncology. Two-hundred and thirty-eight stage III and IV patients were randomized to receive radiation therapy (60 Gy) plus cetuximab and either cisplatin (30 mg/m2) or docetaxel (15 mg/m2) once per week as part of the Radiation Therapy Oncology Group (RTOG) 0234 clinical trial. The 2-year overall survival (OS) was 69% in the cisplatin treatment arm and 79% in the docetaxel treatment arm. The 2-year disease-free survival (DFS) was 57% and 66% in the cisplatin and docetaxel arms, respectively. Previously, two large phase III trials, the RTOG 9501 and the European Organisation for Research and Treatment of Cancer (EORTC) 22931 trials, both showed a small but significant survival benefit for postoperative head and neck cancer patients who received adjuvant radiation and chemotherapy concurrently, resulting in the incorporation of cisplatin in an adjuvant regimen for high-risk patients. The drawback was that adding cisplatin to radiation therapy increased toxicity. Many of these patients are not candidates for the combination therapy due to poor performance status, older age, and renal insufficiency. The purpose of the current trial was to test whether combining a molecular therapy such as cetuximab with chemotherapy would improve survival with a better toxicity profile, [...]

Ten year results of landmark neck cancer trial published

Source: www.modernmedicine.com Author: Gabriel Miller The latest data from a trial that opened in 1992 confirm that for locally advanced laryngeal cancer, sequential and concomitant chemoradiotherapy each produce similar survival rates, but the concomitant approach more often allows the larynx to be preserved. When the results of RTOG 91-11 were first published in 2003. "they changed the standard of care treatment for preserving the larynx from the sequential use of chemotherapy then radiotherapy to giving both together," said lead investigator Dr. Arlene Forastiere of Johns Hopkins University in an email to Reuters Health. "The results have held up over the last decade," she said, "...and this exact treatment remains the standard of care today because on average, 15% will ultimately require laryngectomy with the concomitant approach, compared to double that, or 30%, with either giving chemotherapy and radiation in sequence or giving radiotherapy alone." "There's no question that this study has changed the way we approach and treat this disease, so it is truly a landmark study," said Dr. Chris Holsinger, a head and neck cancer surgeon at MD Anderson Cancer Center in Houston, Texas who wasn't involved in the research. Between 1992 and 2000, 547 patients were randomly assigned to three treatment groups: induction chemotherapy followed by radiation; concomitant chemoradiotherapy; and radiotherapy alone. The induction group received up to three cycles of cisplatin 100 mg/m2 on day one and fluorouracil 1,000 mg/m2 per day for five days, every three weeks. Responders then received up to 70 Gy of radiotherapy [...]

2012-11-30T05:39:25-07:00November, 2012|Oral Cancer News|

Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

Source: Journal of Clinical Oncology Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and Methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 to [...]

2012-06-11T10:02:05-07:00June, 2012|Oral Cancer News|

Tobacco Smoking and Increased Risk of Death and Progression for Patients With p16-Positive and p16-Negative Oropharyngeal Cancer

Source: Journal of Clinical Oncology Abstract Purpose Tobacco smoking is associated with oropharynx cancer survival, but to what extent cancer progression or death increases with increasing tobacco exposure is unknown. Patients and methods Patients with oropharynx cancer enrolled onto a phase III trial of radiotherapy from 1991 to 1997 (Radiation Therapy Oncology Group [RTOG] 9003) or of chemoradiotherapy from 2002 to 2005 (RTOG 0129) were evaluated for tumor human papillomavirus status by a surrogate, p16 immunohistochemistry, and for tobacco exposure by a standardized questionnaire. Associations between tobacco exposure and overall survival (OS) and progression-free survival (PFS) were estimated by Cox proportional hazards models. Results Prevalence of p16-positive cancer was 39.5% among patients in RTOG 9003 and 68.0% in RTOG 0129. Median pack-years of tobacco smoking were lower among p16-positive than p16-negative patients in both trials (RTOG 9003: 29 v 45.9 pack-years; P = .02; RTOG 0129: 10 v 40 pack-years; P < .001). After adjustment for p16 and other factors, risk of progression (PFS) or death (OS) increased by 1% per pack-year (for both, hazard ratio [HR], 1.01; 95% CI, 1.00 to 1.01; P = .002) or 2% per year of smoking (for both, HR, 1.02; 95% CI, 1.01 to 1.03; P < .001) in both trials. In RTOG 9003, risk of death doubled (HR, 2.19; 95% CI, 1.46 to 3.28) among those who smoked during radiotherapy after accounting for pack-years and other factors, and risk of second primary tumors increased by 1.5% per pack-year (HR, 1.015; 95% CI, 1.005 [...]

2012-05-08T09:07:47-07:00May, 2012|Oral Cancer News|

Epidermal Growth Factor Receptor and the Changing Face of Oropharyngeal Cancer

Source: Journal of Clinical Oncology To the Editor: In their article, Chaturvedi et al1 document the rise in human papillomavirus (HPV) –associated cancers as a proportion of squamous cell carcinomas of the oropharynx over the last 25 years. The contemporary figures are mirrored by two recent British studies2,3 demonstrating that the majority of oropharyngeal cancers are now HPV related. In the accompanying editorial,4 Mroz et al rightly highlight the importance of evaluating HPV vaccination for both men and women in the light of these data and lament the lack of significant improvement in the outcomes for non–HPV-associated head and neck cancers. However, they also suggest that the benefit of targeting epidermal growth factor receptor (EGFR) through concurrent cetuximab may be confined to HPV-associated tumors. Although EGFR expression per se does not correlate closely with response to cetuximab, there is increasing evidence of an inverse correlation between p16INK4A expression (as a marker of HPV association) and EGFR expression shown by immunohistochemistry.5,6 Though suppressed by viral oncogenes, HPV-associated tumors retain wild-type P53,7 and patients with this tumor type have demonstrated excellent survival with existing protocols such as concurrent chemoradiotherapy or surgery with postoperative radiotherapy. Conversely, non-HPV tumors, harboring a range of mutations,8 may respond less well to DNA-damaging agents, but patients with these tumors might benefit from the addition of concurrent EGFR blockade to radiotherapy. Data from the recent SPECTRUM (Study of Panitumumab Efficacy in Patients With Recurrent and/or Metastatic Head and Neck Cancer) study of adding another EGFR-targeting monoclonal antibody, panitumumab,9 [...]

2012-03-09T10:34:29-07:00March, 2012|Oral Cancer News|

A Planned Neck Dissection is Not Necessary in All Patients with N2-3 Head-and-Neck Cancer After Sequential Chemoradiotherapy

Source: DocGuide.com PURPOSE: To assess the role of a planned neck dissection (PND) after sequential chemoradiotherapy for patients with head-and-neck cancer with N2-N3 nodal disease. METHODS AND MATERIALS: We reviewed 90 patients with N2-N3 head-and-neck squamous cell carcinoma treated between 1991 and 2001 on two sequential chemoradiotherapy protocols. All patients received induction and concurrent chemotherapy with cisplatin and 5-fluorocuracil, with or without tirapazamine. Patients with less than a clinical complete response (cCR) in the neck proceeded to a PND after chemoradiation. The primary endpoint was nodal response. Clinical outcomes and patterns of failure were analyzed. RESULTS: The median follow-up durations for living and all patients were 8.3 years (range, 1.5-16.3 year) and 5.4 years (range, 0.6-16.3 years), respectively. Of the 48 patients with nodal cCR whose necks were observed, 5 patients had neck failures as a component of their recurrence [neck and primary (n = 2); neck, primary, and distant (n = 1); neck only (n = 1); neck and distant (n = 1)]. Therefore, PND may have benefited only 2 patients (4%) [neck only failure (n = 1); neck and distant failure (n = 1)]. The pathologic complete response (pCR) rate for those with a clinical partial response (cPR) undergoing PND (n = 30) was 53%. The 5-year neck control rates after cCR, cPR→pCR, and cPR→pPR were 90%, 93%, and 78%, respectively (p = 0.36). The 5-year disease-free survival rates for the cCR, cPR→pCR, and cPR→pPR groups were 53%, 75%, and 42%, respectively (p = 0.04). CONCLUSION: In our [...]

2011-12-13T10:52:02-07:00December, 2011|Oral Cancer News|

Implications of the Oropharyngeal Cancer Epidemic

Source: Journal of Clinical Oncology Chaturvedi et al,1 analyzing specimens back to 1984, validate the long-held hypothesis that infection with human papillomavirus (HPV) has increased oropharyngeal squamous cell carcinoma (OPSCC) incidence in the US. They find the incidence of OPSCC in men—who have higher risks of both HPV-positive and HPV-negative OPSCC than women—similar to that of cervical cancer in women. From 1988 to 2004, incidence of HPV-negative OPSCC decreased in parallel with smoking whereas incidence of HPV-positive OPSCC increased at about 7.5% per year, so the percentage of OPSCC that was HPV-positive went from less than 20% to more than 70%. HPV-positive and HPV-negative OPSCC are etiologically and clinically distinct,2,3 with HPV-positive disease having better outcome.4–6 In the current study,1 the hazard ratio of 0.3 for HPV-positive/HPV-negative in survival analysis essentially balances the difference in prevalence so each form of OPSCC now accounts for a similar number of deaths. Notably, the authors found that outcomes for HPV-positive OPSCC have improved over time, whereas outcomes for HPV-negative OPSCC are as dismal as they were 25 years ago. The authors argue convincingly that vaccination to prevent oral HPV infections should be evaluated and that better treatments for both types of OPSCC should be developed. We are unlikely to get a better picture of the recent history of OPSCC in the United States. This study used all available OPSCC specimens from the three Surveillance, Epidemiology, and End Results (SEER) registries that participate in the Residual Tissue Repositories Program, analyzed them in several ways, [...]

2011-11-09T15:24:59-07:00November, 2011|Oral Cancer News|

Palifermin Decreases Severe Oral Mucositis of Patients Undergoing Postoperative Radiochemotherapy for Head and Neck Cancer: A Randomized, Placebo-Controlled Trial

Source: OncologyStat.com TAKE-HOME MESSAGE This randomized, placebo-controlled trial found that weekly palifermin was associated with decreased incidence and duration of severe oral mucositis in patients undergoing postoperative chemoradiotherapy for head and neck cancer. SUMMARY OncologySTAT Editorial Team Combined chemoradiotherapy (CRT) offers improved outcomes after resection of locally advanced head and neck cancer but also increases the risk of oral mucositis, a debilitating and potentially dose-limiting toxicity of locoregional treatment. Palifermin, an analogue of keratinocyte growth factor, is FDA approved to prevent and treat mucositis in patients undergoing high-dose myelotoxic therapy for hematologic malignancies. In this multicenter, randomized, placebo-controlled trial, Henke et al evaluated whether palifermin reduces severe oral mucositis in patients undergoing CRT after surgical resection of locally advanced head and neck cancer. Adult patients receiving postoperative CRT for high-risk stage II to IVB head and neck squamous cell carcinoma and with an ECOG performance status of 0 to 2 were enrolled from 38 centers in Europe, Australia, and Canada. Eligible study patients were stratified by tumor location (oral cavity/oropharynx or hypopharynx/larynx) and residual tumor (R0 [complete resection] or R1 [incomplete resection]). Study patients received a radiation dose of 60 Gy (R0 group) or 66 Gy (R1 group) plus cisplatin 100 mg/m2 on days 1 and 22, with the study drug administered 3 days prior to starting CRT and then weekly for 6 weeks. Patients who underwent radiotherapy after 6 weeks received an additional 100 mg/m2 of cisplatin and study drug. Oral saline rinses, topical anesthetics, feeding tubes, and hematopoietic [...]

2011-09-20T10:21:43-07:00September, 2011|Oral Cancer News|
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