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Articles

Researchers at the NCI have developed the most comprehensive analysis of coding variants in the most frequently studied human tumor cell lines in cancer research.

NCI Releases Largest-Ever Dataset of Genetic Variants in Cell Lines for Nine Types of Cancer

Head and neck squamous cell carcinomas have different patterns of genetic alterations, some of which may be druggable, according to a study by The Cancer Genome Atlas.

Genomic Alterations Characterized in HNSCC

Based on findings from the phase 2b GT-201 and phase 3 ROMAN trials, the FDA has granted priority review to the new drug application for avasopasem manganese as a treatment for radiotherapy-induced severe oral mucositis in patients with head and neck cancer.

FDA Grants Priority Review to NDA of Avasopasem for RT-Induced Severe Oral Mucositis

In an interview with Targeted Oncology, Everett E. Vokes, MD, discussed precision oncology for head and neck cancer and how the molecular biology of head and neck cancers is an opportunity for new investigations and treatment development. 

Precision Oncology Inches into Head and Neck Cancer Paradigm

The FDA has not made a decision on the approval application for toripalimab plus chemotherapy or toripalimab monotherapy for the treatment of advanced recurrent or metastatic nasopharyngeal carcinoma.

FDA Decision on Toripalimab for Advanced Nasopharyngeal Carcinoma Pending Due COVID-19 Travel Restrictions

In an interview with Targeted Oncology, Jimmy Caudell, MD, PhD, discussed the biggest challenges being faced in the head and neck cancer space.

Evaluating the Incidence of HPV-Positive/-Negative, According to NCCN Guidelines 

In an interview with Targeted Oncology, Allan Pickens, MD, discussed research on racial disparities in surgery for esophageal cancer.

Racial Disparities Flood the Esophageal Cancer Space

Jimmy Caudell, MD, PhD, senior member and vice chair for the Clinical Research Department of Radiation Oncology at Moffitt Cancer Center, discusses the overall incidence of human papillomavirus (HPV)-positive and negative oropharyngeal cancers in the United States.

According to Caudell, patients with HPV-positive cancers are overall younger in age while the incidence of HPV-positive oropharynx cancer is increasing among older adults.

However, the overall incidence of HPV-positive oropharynx cancers is increasing in the United States as a whole. At the same time, the incidence of HPV-negative cancer is decreasing. Both are likely linked with the impact of smoking and cancer stage of patients.

 Overall, the incidence of oropharyngeal cancer is relatively stable, but within the incidence of HPV-positive oropharyngeal cancer, it is increasing quite rapidly, whereas HPV-negative, at least in the United States, is decreasing. Recent publications released in the last 5-10 years consider HPV-related oropharyngeal cancer to be an epidemic.

Similar to many other smoking-related cancers, HPV-negative cancers of the head and neck have been decreasing because people have been smoking less or not smoking at all. HPV-positive oropharyngeal cancer is increasing in incidence because, at the base of it, it is a sexually transmitted disease.

Videos

Jimmy Caudell, MD, PhD, discusses the overall incidence of human papillomavirus-positive and negative oropharyngeal cancers in the United States.


News

Varying Incidence of HPV-Positive and Negative Oropharyngeal Cancers

Jean Bourhis, MD, a professor of radiation oncology at the University of Paris, discusses results from the phase 2 study of xevinapant plus chemoradiation vs placebo and chemoradiation in patient with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN; NCT02022098).

Results from the 5-year analysis of the study were presented during the European Society of Medical Oncology Congress 2022 by Bourhis. It was shown that the addition of xevinapant to standard-of-care chemoradiation improved the durability of responses in patients with LA SCCHN.

The study was a phase 2 randomized trial comparing placebo versus xevinapant with standard of care in patients with locally advanced from cell carcinoma the head and neck. These patients were really high-risk patients, the most advanced among the locally advanced cases. And we knew already that xevinapant was active and well tolerated in the same study. tThe results that we presented [at ESMO] are long-term follow up results. And especially we have data here on overall survival at 5 years, which we didn't have before.

 What do we see here in this study with long-term follow up the 5-year overall survival is markedly improved with the xevinapant when compared to placebo. And there is nearly a doubling of the overall survival at 5 years. The data [shows that] it's from 28%, with placebo to 53% with xevinapant and we can say that in this selection of patients, again with really high-risk, locally advanced squamous cell cancer of the head and neck. This is something we've never seen in the last 3 decades because the standard of care, cisplatin radiotherapy, has never been improved with the new treatme

Jean Bourhis, MD, discusses results from the phase 2 study of xevinapant plus chemoradiation vs placebo and chemoradiation in patients with locally advanced squamous cell carcinoma of the head and neck.

Duration of Response With Xevinapant Plus Standard Chemoradiation in LA SCCHN

Joseph M. Curry, MD, a professor in the department of otolaryngology and vice chairman of research at Thomas Jefferson University, discusses the introduction of immune checkpoint inhibitors (ICIs) for the treatment of patients with head and neck cancers.

Anti–PD-1 therapies have shown efficacy in head and neck cancer in clinical trials, leading to the approval of pembrolizumab (Keytruda) based on the KEYNOTE-012 trial (NCT01848834), and nivolumab (Opdivo) based on the CheckMate 141 trial (NCT02105636) for recurrent and metastatic head and neck squamous cell carcinoma. Curry notes that pembrolizumab is now considered first-line therapy for unresectable metastatic disease based on the results of the KEYNOTE-048 trial (NCT02358031).

ICIs also have potential for use in the neoadjuvant setting even for resectable disease. Curry and other investigators are conducting a phase 1 trial (NCT03618654) of durvalumab (Imfinzi) and metformin in head and neck squamous carcinoma. The trial is exploring the efficacy of PD-1 inhibition in the 4-week window prior to surgery, indicating that ICIs play multiple valuable roles in treating head and neck cancer.

 ICIs have been a popular and exciting development because of the efficacy they've shown in head and neck cancer—specifically within head and neck cancer, anti–PD-1 therapy. So, both pembrolizumab and nivolumab have been approved for the treatment of recurrent and metastatic head and neck cancer and squamous cell carcinoma because of the efficacy that they've shown in a number of clinical trials. And in fact, after the initial approval, they've moved up in the algorithm such that pembrolizumab is now included in first line therapy for metastatic and inoperable disease.

And so, these therapies have really expanded what we think of as options in terms of non-surgical therapies. And in terms of this specific clinical trial, they've also expanded how we approach disease, which is in some cases operable, looking at neoadjuvant strategies for the use of immune checkpoint inhibitors.

Joseph M. Curry, MD, discusses the introduction of immune checkpoint inhibitors for the treatment of patients with head and neck cancers.

Immune Checkpoint Inhibitors Offer New Approaches in Head and Neck Cancer

Christine Dierks, MD, senior physician at the University Hospital Freiburg in Germany, describes the prognosis of the anaplastic thyroid carcinoma and differentiated thyroid cancer populations.

Dierks says that the prognosis is very poor for both patient populations but especially for those with anaplastic thyroid carcinoma. Poor outcomes are seen with patients who have anaplastic thyroid carcinoma even if they have combined therapy, which can include surgery and radiotherapy, followed by chemotherapy. In these patients, the life expectancy is about 4 to 5 months after therapy, according to Dierks.

In terms of survival, there is an exception for patients who had 

-positive disease because imatinib (Gleevec) is available for these patients. Dierks notes that for the other 80% of patients, the prognosis remains poor due to a lack of agents.

Christine Dierks, MD, describes the prognosis of the anaplastic thyroid carcinoma and differentiated thyroid cancer populations.










Outcomes Underscore Need for New Agents to Treat Anaplastic Thyroid Carcinoma

Christopher Nutting, MD, joint head of the Division of Radiotherapy and Imaging at The Institute of Cancer Research and consultant clinical oncologist at The Royal Marsden, discusses the results of a randomized phase 3 trial using dysphagia-optimized intensity modulated radiotherapy (Do-IMRT) versus standard IMRT (S-IMRT) in patients with head and neck cancer.

This study included 112 patients who were randomized 1:1 to receive either S-IMRT or Do-IMRT. The primary end point was the MD Anderson Dysphagia Inventory (MDADI), which was collected 12 months after patients completed treatment. Most of the patients were male, and the most common tumor location was the oropharynx. Among the patients participating, 90% had prior chemotherapy and radiation, which is standard protocol in this setting. A majority of patients were human papilloma virus-positive, which is a group with good long-term prognosis for carrying the burden of the treatment, according to Nutting.

Nutting says the first finding in the study was that the investigators were able to reduce the radiation dose to the muscles in the experimental arm, which is what the investigators were hoping for. The MDADI score at 12 months was about 70 points out of 100 in the group of patients receiving S-IMRT, which is expected in pretrial analyses. The Do-IMRT group had about 78 points for the MDADI score. This was statistically significant, with a 

value of 0.016. A score difference of 5 to 10 points is considered to be a clinically relevant improvement in the MDADI score, he explains.

<< View more resources and information in head and neck cancers

Christopher Nutting, MD, discusses the results of a randomized phase 3 trial using dysphagia-optimized intensity modulated radiotherapy versus standard IMRT in patients with head and neck cancer.

Dysphagia-Optimized IMRT Shows Significance in Head and Neck Cancer

Robert L. Ferris, MD, PhD, director of the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center; Hillman Professor of Oncology; associate vice chancellor for cancer research; professor of otolaryngology, immunology, and radiation oncology; co-director, Tumor Microenvironment Center, discusses the rationale for evaluating STING agonists as treatment for patients with head and neck cancers. ADU-S100/MIW815, in particular, is under evaluation in combination with the checkpoint inhibitor pembrolizumab (Keytruda) in the phase II ADU-CL-20 clinical trial for patients with PD-L1–positive recurrent or metastatic squamous cell carcinoma of the head and neck.

The compound is a proinflammatory agonist that stimulates the STING pathway, says Ferris. Data have shown that the STING pathway is an important inflammatory pathway in a number of epithelial cancers, including head and neck cancer.

Data suggest that intralesional and intratumoral injection with a STING agonist, such as ADU-S100/MIW815 and other compounds that stimulate the STING pathway, can trigger beneficial inflammation and draw immune cells into the tumor microenvironment, says Ferris. This was the rationale for evaluating this agent in combination with an immune checkpoint inhibitor in the phase II study.

Robert L. Ferris, MD, PhD, discusses the rationale for evaluating STING agonists as treatment for patients with head and neck cancers. 

Rationale for Evaluating STING Agonists in Head and Neck Cancer

Standard Approach to Treating DLBCL

Treatment Limitations in DLBCL

Selecting Therapy for Relapsed-Refractory DLBCL

Anti-CD19 Monoclonal Antibody Therapy in DLBCL

CAR T-Cell Therapy in DLBCL

Tailoring Therapy for Patients With DLBCL

DLBCL

Bladder Cancer

Emerging Data in R/R DLBCL

Marcelo C. Pasquini, MD, associate professor of medicine, Medical College of Wisconsin and senior scientific director of Center for International Blood and Marrow Transplant Research (CIBMTR) Clinical Trials Support, discusses the rationale for analyzing real-world data for the use of tisagenlecleucel (Kymriah), a chimeric antigen receptor (CAR) T-cell therapy, as a treatment for patients with acute lymphoblastic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL). This CD19 CAR T cell was approved 2 years ago for use in both ALL and DLBCL.

When the FDA approved the CAR T cell, the FDA mandated that the industry develop an infrastructure to follow these patients long-term as part of the approval process. There were concerns over whether these patients would develop secondary malignancies in the process of manufacturing the cells, so patients had to be followed for 15 years.

Marcelo C. Pasquini, MD, discusses the rationale for analyzing real-world data for the use of tisagenlecleucel, a chimeric antigen receptor T-cell therapy, as a treatment for patients with acute lymphoblastic leukemia and diffuse large B-cell lymphoma. This CD19 CAR T cell was approved 2 years ago for use in both ALL and DLBCL.

Analyzing Real-World Data for CAR T-Cell Therapy in Patients With ALL and DLBCL

TRK as Ideal Candidate for Targeted Therapy

Scientific Rationale for Development of TRK Inhibitors

Early Development of TRK Inhibitor-Larotrectinib

Efficacy of TRKi-Larotrectinib Among Tumor Types

Safety and Efficacy Profile for TRKi-Larotrectinib

Patient Selection for TRKi-Larotrectinib

TRKi: High Response Rate in Patients With Primary CNS Disease

Entrectinib-A Multitargeted TKI

Entrectinib-Selective ROS Inhibition

Investigational Approaches for TRK-Fusion Cancers

NGS Testing to Detect TRK Fusions

Molecular Testing for RAI-Refractory Thyroid Cancer

Dirty Kinases in TRK-Fusion Malignancies

Prostate Cancer

Ovarian Cancer

Colorectal Cancer

EGFR+ Lung Cancer

TRK Inhibitors: A Tumor Agnostic Approach to Treatment of Solid Tumors

Danny Rischin, MD, director, Division of Cancer Medicine, head, Department of Medical Oncology, Peter MacCallum Cancer Centre, discusses results from the protocol-specified final analysis of the phase III KEYNOTE-048 trial of pembrolizumab (Keytruda) as frontline therapy for recurrent/metastatic head and neck squamous cell carcinoma.

Conference News

Final KEYNOTE-048 Results With Frontline Pembrolizumab in Recurrent/Metastatic HNSCC

In the coming years, we are going to continue to see the development and FDA approval of a lot of novel targeted drugs for patients with relapsed large-cell lymphoma. And I think specifically, a lot of these drugs are being developed for patients who are failing a transplant, or are ineligible for a transplant, or cannot get into a remission with salvage chemotherapy. I mentioned tafasitamab. I talked a little about CAR [chimeric antigen receptor] T cells, polatuzumab. There are several other drugs also being developed in this space, which are biological, and some of them are targeted drugs.

As we move forward, as these drugs all become available to the clinician, the big thing is going to be deciding which of these drugs to use in which patient populations. This decision should be based on the drug&rsquo;s adverse-effect profile, as well as the activity of the drug. In patients, for example, who potentially have compromised organ function, we might not want to use drugs like CAR T cells that could have a really tough effect on their performance status, or drugs that maybe affect heart function or kidney function.

In patients who are of great performance status and are great candidates, I would probably pick CAR T-cell therapy. In patients who are older and have compromised organ function, I might be thinking about a more biological regimen, like tafasitamab plus lenalidomide or, potentially, an emerging novel biological regimen. It&rsquo;s important to look at the entire profile of the drug, or of the combination, when you&rsquo;re making these decisions. Again, not only adverse effects but also what the goals of therapy are and what the activity of the combination or the single drug is that you&rsquo;re planning on using.

Thank goodness there are a lot of other things in this space. There are a lot of drugs that are being developed for patients who either relapse after a transplant, or are ineligible for a transplant, or cannot get into remission prior to transplant. There recently was the FDA approval of the combination of the drugs bendamustine-rituximab plus polatuzumab. This is an anti-CD79b antibody, and this is also approved in patients with relapsed large-cell lymphoma.

There are ongoing trials with many other targeted drugsdrugs that are targeting different cell surface antigens. We have several combination trials ongoing looking at the potential benefit of drugs like venetoclax and other next-generation immunomodulatory drugs. Hopefully, as these trials continue to progress, we&rsquo;ll see other good options for patients with relapsed large-cell lymphoma.

I think 1 of the most exciting things to come out in the last couple [of] decades for large-cell lymphoma is CAR [chimeric antigen receptor] T-cell therapy. The reason CAR T cells are so exciting is because they use a very novel mechanism to target the relapsed large-cell lymphoma. This is a mechanism, or I should say an approach that has been very successful in children with relapsed B-cell leukemia, and is also being used in many other different types of B-cell malignancies. Essentially, what we do is take the patient&rsquo;s own T cells and train them in the lab to recognize cancer cells. These T cells are then reinfused into a patient, where they expand and then go on the attack. What happens is these T cells then find, recognize, and kill malignant B cells within the patient.

These approaches, again using CAR T cells in relapsed large-cell lymphoma, have been associated with long-term or durable remissions in anywhere from 30% to 50% of patients. Many of these patients had failed a prior autologous stem cell transplant or were ineligible for a stem cell transplant. Again, the most exciting thing is not just how they work but that these drugs are working very well, potentially curing patient populations for which we did not have a lot of options previously.

These drugs are associated with adverse effects, so they are not without risk. Many times, patients can develop very severe cytokine release syndrome. This is a syndrome that can lead to multiorgan damage. It can sometimes lead to very severe neurological changes in the patientseverything from seizures, to patients having respiratory failure, to confusion. Unfortunately, at least today, we do not have a good way to predict for whom or when adverse effects will occur.

Many of these patients are watched very closely for the first 2 weeks after receiving CAR T cells. It&rsquo;s quite uncommon to have late adverse effects with CAR T cells, with the exception of cytopenias. If patients make it the first 2 weeks and have a remission, especially a complete remission, it&rsquo;s likely that they can maintain a durable remission or a cure. So these are very exciting times.

HEAD & NECK CANCERS

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