Giving hope: research on rare head and neck cancer treatment options

Source: www.curetoday.com
Author: Antonia DePace

Findings from a phase 3 clinical trial demonstrated improved tumor shrinkage rates with the immune checkpoint inhibitor toripalimab and a first-line chemotherapy combination for nasopharyngeal carcinoma, a tumor that occurs in the nasopharynx (located behind the nose and above the back of the throat). The promising results may open the door to new clinical trials assessing triplet therapies with Food and Drug Administration (FDA)-approved drugs and provide hope for better treatment options for this patient population.

Results from the JUPITER-02 trial were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. In 2020, toripalimab received a breakthrough-therapy designation (approval to expedite drug development) for metastatic nasopharyngeal carcinoma. Of note, toripalimab is approved in China for several indications, but it is not FDA approved.

Currently, the worldwide standard of care for these patients is first-line chemotherapy with gemcitabine and cisplatin. “By adding immunotherapy to the combination, we hope to improve survival and increase the time from starting therapy to progression of the cancer,” said Dr. Glenn Hanna, director of the Center for Salivary and Rare Head and Neck Cancers at Dana-Farber Cancer Institute in Boston, in response to the trial results. “If the triplet (therapy) has better rates of tumor shrinkage and prolongs survival with a reasonable side effect profile, that’s a win.”

The possible addition of a novel regimen is exciting. “Treatment advances for late-stage nasopharyngeal carcinoma have lagged behind those of other cancers,” Dr. Julie R. Gralow, ASCO chief medical officer and executive vice president, said in a news release. “Findings from the JUPITER-02 study offer new hope for patients with advanced disease, changing how we care for them.”

The trial was performed in China, and researchers observed an improved median progression-free survival (the length of time during and after treatment of a disease that a patient lives with the disease without it getting worse) of 11.7 months with the treatment regimen of toripalimab plus gemcitabine and cisplatin compared with eight months in patients treated with chemotherapy alone.

“It does get a little tricky when they’re testing an agent that’s primarily manufactured and approved in another country, but we did see practice-changing results,” said Dr. Malini Patel, a medical oncologist in the lung cancer/thoracic oncology and head and neck oncology programs at Rutgers Cancer Institute of New Jersey. “I’m fairly confident that in the near future, we should be able to see this drug in the United States.”

Patel noted that new clinical trials are underway replicating a similar treatment regimen with already-approved checkpoint inhibitors. “(JUPITER-02) is the first study to show a response like this in the first- line, recurrent and metastatic setting, and there are other trials using agents that we use in the United States that are piggybacking off this design,” she explained.

Hanna noted a new trial by the nonprofit research organization NRG Oncology, which is examining the efficacy of gemcitabine and cisplatin in combination with Opdivo (nivolumab). The hope is to see similar, if not identical, results by using the FDA-approved immune checkpoint inhibitor Opdivo in place of the not-yet-approved toripalimab. “The concept is built on the success that’s been observed in Asia,” he said. “I think it will be an analogous study in our population. So, hopefully, we see similar results.”

Both Hanna and Patel acknowledged, however, the possibility of seeing different results due to the difference in populations. Nasopharyngeal carcinoma is considered endemic in Southern China, Southeast Asia and Northern Africa, whereas it’s rare in the United States, with less than 1 case per 100,000 people each year, according to the American Cancer Society.

Although the exact reason for the uneven geographic distribution is unknown, it is partly due to the association with Epstein-Barr virus (EBV) — the infection of nasopharyngeal epithelial cells — that differs between the populations. EBV is known to increase the risk of developing various diseases, including nasopharyngeal carcinoma. “There are some EBV-associated endemic nasopharyngeal carcinomas that we see in the United States, primarily from those who migrate from areas of high risk to areas of low risk, but we encounter more smoking-related, non-EBV-related nasopharyngeal carcinomas (in the United States),” Patel explained.

Patel added that this doesn’t change the importance of the trial results. “I don’t think it should underscore the results of the study,” she emphasized. “Our survival data (are) certainly immature, but we do see a trend for improvement in survival.”

In addition to these studies, other trials have examined the use of drugs such as Keytruda (pembrolizumab) and Opdivo as single agents for the treatment of nasopharyngeal carcinoma. Hanna also noted that exciting new therapies targeting the EBV virus are on the horizon, as are studies combining immunotherapy with vascular targeting drugs, but that agreement on an official second-line treatment option remains an open question.

“Right now, outside of a clinical trial, it’s a little bit heterogeneous in what doctors prescribe and use. We are in need of trials that focus on the population that (progressed after) chemotherapy and immunotherapy in the first-line setting,” he explained. “It’s a tough disease to treat.”

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 favorable prognosis with improved rates of response prognosis with improved rates of response to treatment and overall survival. Because of the difference in tumor biology, the National Comprehensive Cancer Network (NCCN) has adopted different staging criteria for HPV+ and HPV– disease and recommends that HPV status be used to stratify patients with OPC.1

The treatment landscape for localized OPC typically involves a multidisciplinary approach consisting of chemotherapy, radiation, and/or surgery. For fit patients with locally advanced OPC who are able to tolerate intensive therapy, concurrent radiation with systemic high-dose cisplatin chemotherapy is the preferred treatment regimen.1 Unfortunately, treatment of OPC is associated with a high risk of treatment-related morbidity, which may leave patients cured of their malignancy but with lifelong complications, such as dysgeusia, dysphagia, and xerostomia, but also systemic complications from cisplatin chemotherapy, including hearing loss and neurotoxicity.

Because patients with HPV+ OPC are generally younger with more favorable prognoses, clinicians have hypothesized that less intensive treatment could result in fewer long-term complications from treatment but with continued favorable cancer-related outcomes.5 This concept, called deintensification, has become popular in recent years. Several strategies for treatment deintensification have been proposed, including reducing the dose of radiation; substituting cisplatin for an alternative agent with less toxicity, such as cetuximab; and surgical resection. Several phase 3 comparison trials have been conducted, and other trials are ongoing.

Aptly named De-ESCALaTE (NCT01874171), this phase 3 trial randomized patients with 334 HPV+ OPC to receive radiation plus cetuximab or cisplatin.6

Unfortunately, the trial results did not favor substitution of cisplatin with cetuximab. At 2 years, the incidence of severe toxicities did not significantly differ between cetuximab and cisplatin (P = .98), nor did rates of overall toxicities (P = .49). Significant differences in 2-year overall survival rates and recurrence rates were seen. However, these results favored cisplatin (HR, 5.0; P = .001 for overall survival; HR, 3.4; P = .0007 for recurrence).6

RTOG-1016 (NCT01302834) was a second phase 3 trial published comparing cetuximab with cisplatin in HPV+ OPC patients.7 This trial analyzed 805 patients who were randomized to receive radiation plus cetuximab or cisplatin. Similar to the De-ESCALaTE trial, the RTOG-1016 trial results favored cisplatin over cetuximab, with 5-year overall survival rates of 84.6% versus 77.9%.8

Because of the De-ESCALaTE and RTOG-1016 results, experts advise against the substitution of cisplatin for chemoradiation regimens for patients with localized HPV+ OPC, and cisplatin plus radiation continues to be the preferred systemic treatment option per the NCCN guidelines.1,5 Because cisplatin continues to be standard of care for the treatment of localized OPC, the role of deintensification for patients with HPV+ OPC may lie in adjustments to surgical strategies or radiation therapy. Treatment deintensification should be pursued only through clinical trials, and experts encourage clinicians to conduct and analyze phase 2 trials before moving on to phase 3 studies.1,5

CONCLUSION
The treatment landscape of cancer is ever-changing. Specifically in localized HPV+ OPC, the difference in tumor biology presents a unique clinical area where reducing the intensity of treatment may be warranted, particularly with long- and short-term toxicities associated with cisplatin. Interestingly, phase 3 data have shown evidence of harm in removing cisplatin from chemoradiation regimens for HPV+ OPC; therefore, cisplatin-based chemoradiation remains the standard of care for these patients. Future trials may support treatment deintensification in ways other than removing cisplatin.

REFERENCES
1. NCCN. Clinical Practice Guidelines in Oncology. Head and neck cancers, version 3.2021. Accessed June 16, 2021. https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf

2. Cancer stat facts: oral cavity and pharynx cancer. National Cancer Institute. Accessed June 16, 2021. https://seer.cancer.gov/statfacts/html/oralcav.html

3. Genital HPV infection – fact sheet. CDC. Updated January 19, 2021. Accessed June 17, 2021. https://www.cdc.gov/std/hpv/stdfact-hpv.htm
4. HPV and oropharyngeal cancer. CDC. Updated September 3, 2020. Accessed June 17, 2021. https://www.cdc.gov/cancer/hpv/basic_info/hpv_oropharyngeal.htm

5. Mehanna H, Rischin D, Wong SJ, et al. De-escalation after DE-ESCALATE and RTOG 1016: a head and neck cancer intergroup framework for future de-escalation studies. J Clin Oncol. 2020;38(22):2552-2557. doi:10.1200/JCO.20.00056

6. Mehanna H, Robinson M, Hartley A, et al; De-ESCALaTE HPV Trial Group. Radiotherapy plus cisplatin or cetuximab in low-risk human papillomavirus-positive oropharyngeal cancer (De-ESCALaTE HPV): an open-label randomised controlled phase 3 trial. Lancet. 2019;393(10166):51-60. doi:10.1016/S0140-6736(18)32752-1

7. Gillison ML, Trotti AM, Harris J, et al. Radiotherapy plus cetuximab or cisplatin in human papillomavirus-positive oropharyngeal cancer (NRG Oncology RTOG 1016): a randomised, multicentre, non-inferiority trial. Lancet. 2019;393(10166):40-50. doi:10.1016/S0140-6736(18)32779-X

8. Gardasil 9. Prescribing information. Pfizer; 2017. Accessed June 23, 2021. https://www.fda.gov/fi les/vaccines,%20blood%20&%20biologics/published/Package-Insert—Gardasil.pdf

Henderson throat cancer patient rallies after cutting-edge treatment

Source: www.reviewjournal.com
Author: Mary Hynes, Las Vegas Review-Journal

In February, a cancerous tumor caused extreme swelling in Ruben Solis’ neck and face, blocking his airway. After an emergency tracheotomy, an incision to his windpipe that allowed him to breathe, Solis had to decide whether he wanted to enter a clinical trial to receive an experimental treatment.

The 54-year-old Henderson resident was skeptical. But with stage 4 laryngeal cancer that had spread to his lungs, he was running out of options. Three months later, after three treatments, the tumors in his throat and lungs have dramatically shrunk and the swelling subsided.

“I feel much better,” Solis said Monday.

The father and grandfather, who worked in banquets and as a food and beverage manager on the Strip before falling ill, is the first person in the world to receive a combination of two experimental drugs, Enoblituzumab and Retifanlimab, as part of a new clinical trial for head and neck cancer, according to Comprehensive Cancer Centers of Nevada, the local site participating in the global study.

Solis and his oncologist, Dr. Anthony Nguyen, spoke with reporters prior to the patient receiving his fourth infusion of the two drugs. The treatment is a new form of immunotherapy, which boosts the body’s immune system to combat the cancer.

“So his immune system is actually being manipulated, turned on, to actually fight the cancer from inside,” Nguyen said.

In this way it is different from traditional chemotherapy.

“When we think of chemotherapy and cancer medicine, we think of dropping bombs on the cancer, and the bombs will kill the cancer, but they also will hurt the surrounding tissue in the person as well,” Nguyen said. “So we’re trying to move away from traditional chemotherapy and customize it to provide something that’s a lot easier” for patients to tolerate.

The combination of drugs was customized to fit the unique molecular profile of Solis’ tumor.

The tumor in Solis’ throat grew to about an inch and a half in diameter, causing severe swelling of the neck and face, the oncologist said. A Comprehensive Cancer Centers publicist wrote to reporters that the mass grew to the size of “a football,” though Nguyen said the swelling gave the patient’s head and neck the appearance of a watermelon.

Solis, who was diagnosed with cancer in December 2019, was at first treated with more standard radiation and chemotherapy. The cancer went into remission, only to return and to spread.

The sponsor of the trial is biopharmaceutical company MacroGenics, based in Rockville, Maryland. The trial, with about 80 participants, will take place in 35 centers in the U.S., Australia and Europe.

Comprehensive Cancer Centers of Nevada is involved in about 170 clinical trials, 86 of which are in the active phase; in the remainder, the patients continue to be evaluated after the completion of the treatment phase. Medications in the trials are provided free.

Through such trials in Southern Nevada, “We’re crushing that notion that one has to travel far to get cutting edge, new medicines that are not FDA approved or not available,” Nguyen said.

New therapy shortens treatment for HPV-related cancers of the tonsils, tongue

Source: medicalxpress.com
Author: From Mayo Clinic News Network, Mayo Clinic News Network

Patients with HPV-related oropharyngeal cancer who undergo surgery and are treated with chemotherapy, may be able to forgo significant radiation therapy without increasing the risk of their cancer spreading, according to the results of a clinical trial led by researchers at Mayo Clinic.

“We found that decreasing the amount of radiation therapy after a minimally invasive robotic surgery improved the quality of life of patients with HPV-related oropharyngeal cancer while delivering excellent cure rates,” says Dr. Eric Moore, a Mayo Clinic otolaryngologist. “In essence, we found exactly the right amount of treatment to deliver without over-treating these patients.”

Dr. Moore and his colleagues compared 79 patients treated at Mayo Clinic for HPV-related tonsil and tongue cancer with surgery and two weeks of radiation therapy to a group of 115 patients with the same cancer who were treated with surgery, and the standard six weeks of radiation therapy and chemotherapy.

Dr. Moore and his colleagues found no decrease in survival or cancer recurrence in the group that received two weeks of radiation therapy, compared to the group that received six weeks of radiation therapy. He says that by decreasing the amount of radiation therapy after minimally invasive robotic surgery, physicians were able to improve the quality of life of patients and achieve excellent cure rates.

“In essence, we found exactly the right amount of treatment to deliver without overtreating,” says Dr. Moore.

Dr. Moore says Mayo Clinic now offers dose de-escalation radiation therapy to appropriately selected patients with HPV-related cancers of the tonsils and tongue.

“This approach shortens the treatment time for these patients by several weeks and reduces side effects without sacrificing the effectiveness of the treatment,” Dr. Moore says.

Deal-making in head and neck cancer to start yielding dividends for patients

Source: www.thepharmaletter.com
Author: staff

A frenzy of deal-making activity in head and neck cancer is bringing late-stage clinical candidates into view, according to GlobalData.

Intelligence from the data and analytics provider shows that there have been some 340 licensing agreements since 2004 in head and neck cancer, amounting to an approximate total value of $35 billion.

Aarohi Rede, oncology analyst at GlobalData, said: “The past few years have seen several licensing deals globally for clinical development in head and neck cancer. Merck KGaA’s collaboration with Debiopharm has the potential to transform the current treatment paradigm for head and neck squamous cell carcinoma (HNSCC) by combining xevinapant, a new molecular entity, with Merck KGaA’s strong commercialization capabilities.”

Of the total licensing agreements signed, the highest recorded licensing agreements took place in North America, followed by Asia-Pacific, while the lowest recorded number of deals belonged to South and Central America.

Dr Rede added: “Head and neck cancer is largely a chemotherapy-dominated market, but the past few years have seen effective use of Keytruda (pembrolizumab) and Bristol Myers Squibb’s Opdivo (nivolumab) in the recurrent or metastatic settings. The current clinical development pipeline has around 20 late-stage agents in the immuno-modulating therapy or cell inhibitor classes, thus revealing a robust late-stage pipeline that is highly conducive to future partnerships for licensing and commercialization, and is expected to contribute to significant market growth over the next ten years.”

Many of these licensing deals involve strategic partnerships between Asia-Pacific, namely Chinese manufacturers, and US pharmaceuticals for joint clinical and commercial development of oncology assets, with the purpose of gaining market access in the USA.

“While the currently marketed agents are patent protected, the introduction of drugs through these alliances poses competition for some of the premium-priced therapies, both from a market share and price perspective,” Dr Rede said.

“While licensing agreements have been one of the key business development tactics in oncology, venture financing ($8.6 billion valuation), asset transactions ($4 billion valuation), and contract service agreements ($30 million valuation) are some of the other investment approaches considered in recent years to advance drug development science in the head and neck space by way of investment capitalism.”

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 receive cisplatin. Generally, we reserve definitive radiation alone options for patients who are completely ineligible for any systemic therapy.

If definitive therapy would be considered too difficult, or for those who have metastatic disease, still other palliative regimens are available.

When should clinicians consider nivolumab or pembrolizumab?
Jhawar:
At this time, immuno-oncology agents such as nivolumab or pembrolizumab are approved and used regularly only in the recurrent or metastatic setting. Even in the recurrent setting, they are generally considered only if surgery or re-irradiation therapy is not an option.

These novel agents should only be considered earlier in a patient’s treatment course in place of more traditional systemic options via a clinical trial.

What are the potential benefits of the combined use of immunotherapy, chemotherapy, and vaccines?
Jhawar:
The potential benefits of combination strategies using checkpoint inhibitors and other immuno-oncology treatments, including vaccines, in combination with more traditional therapies including surgery, radiation, and chemotherapy are still being worked out. It is likely that we will first see applications of these newer therapies in the recurrent and metastatic setting, but they may be incorporated earlier into patient care as more data about safety and efficacy emerges.

We have seen regular use of immuno-oncology treatments in other disease sites, and these therapies are being introduced earlier in the treatment course for patients. I would expect a similar pattern to emerge for HNSCC, although we will need to wait for phase III randomized controlled trial data for these immunotherapies to be ready for prime time.

It should be noted, however, that given the heterogeneity of HNSCC, there are certain scenarios in which we are working towards de-escalation of therapy, and addition of more therapies may not be needed.

In the patients with HPV-positive oropharyngeal squamous cell carcinoma and less than 10 pack-year smoking histories, the cure rates are more than 90% with current standard-of-care treatment. We are now working towards de-escalating therapy. It is not clear what role, if any, immuno-oncology will play in these already favorable situations.

What about the potential synergy of molecular targeted agents with radiation?
Jhawar:
There are multiple potential targets that could lead to synergy with radiation. Cetuximab actually acts on one of these targets, the epidermal growth factor receptor. Other potential targets that are being studied for combinations with radiation include cell signaling pathways (mTOR, AKT), cancer metabolism, tumor hypoxia, and DNA repair pathways (PARP, ATR).

There are other studies that have been completed or are ongoing that use agents to improve radioprotection of normal tissues. To date, none of these targeted agents are being regularly used on their own or in combination in the care of patients outside of clinical trials.

What improvements with new targeted therapies and immunotherapies do you foresee?
Jhawar:
As our understanding of the molecular mechanisms of carcinogenesis, aberrant cancer signaling pathways, and the tumor microenvironment improves, I expect that the number of targets and, therefore, the number of molecular targeted agents will grow. This will lead to a large increase in the number of clinical trials and expansion of our armamentarium against HNSCC.

Similarly, as our understanding of the interplay between cancer and the immune system and mechanism of immune escape improves, I suspect we will be able to improve response rates from immuno-oncology drugs. Currently, only 10% to 20% of patients respond to immuno-oncology treatments, leaving a great deal of room for improvement.

Taken together, this will allow for more individualized, patient-specific care and afford the ability to test novel combinations to improve cure rates. Simultaneously, this will decrease toxicity by choosing the right treatment for the right patient, rather than having a one-size-fits-all approach to therapy.

What’s the take-home message for practicing oncologists?
Jhawar:
There is a great deal of change forthcoming in the treatment of HNSCC, but at this time standard-of-care therapy still consists of some combination of traditional cancer therapies, including radiation, surgery, and chemotherapy.

Read the study here and expert commentary about the clinical implications here.

Thousands of Britons with deadly mouth cancer will be spared gruelling chemotherapy thanks to immune-boosting drug

Source: www.dailymail.co.uk
Author: Eve Simmons for The Mail on Sunday

Thousands of Britons with deadly mouth cancer will now be spared grueling chemotherapy thanks to an immune-boosting drug. The treatment, given the green light by health chiefs last week, offers fresh hope to patients whose cancer has either spread or deemed inoperable.

Currently, these patients have two options to prolong their life – chemotherapy and weekly infusions of potent cancer drugs, which often leave patients debilitated and confined to bed for the short time they have left. But now immunotherapy drug pembrolizumab can help some patients with the disease live up to 30 per cent longer than they would with chemotherapy, with 50 per cent fewer side effects.

Last week’s ruling by UK health watchdog NICE, which was based on the results of final-stage international trials, permits the treatment not only for advanced mouth cancer but also cancers of the nose, sinuses and salivary glands, known collectively as head and neck cancers.

Doctors must first test patients’ tumours for a protein called PD-L1, which limits the immune system’s ability to find and destroy the cancer.

Immunotherapy drugs such as pembrolizumab blocks PD-L1, helping the body’s fighter cells to attack tumours.The majority of people with advanced head and neck cancer will test positive for PD-L1.

Roughly 12,000 Britons are diagnosed with these cancers every year – mostly men over the age of 70. In the majority of cases, head and neck cancers are spotted at a late stage as they are often mistaken for other less serious conditions. By the time they are diagnosed, the cancer has spread to other nearby tissues and prognosis is poor, with many surviving just six months.

Researchers from the Institute of Cancer Research who trialled the new drug discovered that some patients lived for more than a year following pembrolizumab treatment. Pembrolizumab is already used widely on the NHS to treat skin, bladder and small cell lung cancers.

Professor Kevin Harrington, consultant clinical oncologist at The Royal Marsden Hospital in London, welcomed the decision. He said: ‘Pembrolizumab can improve survival, while avoiding some of the most challenging side effects.’

Prof Harrington said he was ‘disappointed’ that health chiefs did not extend approval for combination therapy – using pembrolizumab alongside chemotherapy, which is shown to have the most significant impact on survival.

He remains ‘hopeful’ that NICE may go further and fund combination therapy in the future, for those whom it is appropriate.

Home-based chemo skyrockets at one US center

Source: www.medscape.com
Author: Nick Mulcahy

In the fall of 2019, the University of Pennsylvania in Philadelphia started planning a pilot program of home-based chemotherapy for two treatment regimens (one via infusion and one via injection). Six months later, the Cancer Care at Home program had referred 40 patients.

The uptake within the university’s large regional health system was acceptable but not rapid, admitted Amy Laughlin, MD, a hematology-oncology fellow involved with the program.

Then COVID-19 arrived, along with related travel restrictions.

Suddenly, in a 4-week period (March 10 to April 7), an additional 135 patients had been referred ― a 300% increase from earlier. The list of chemotherapies delivered went from two to seven, with more coming.

“We’re not the pilot anymore ― we’re the standard of care,” Laughlin told Medscape Medical News.

“The impact [on patients] is amazing,” she said. “As long as you are selecting the right patients and right therapy, it is feasible and even preferable for a lot of patients.”

For example, patients with hormone-positive breast cancer who receive leuprolide (to shut down the ovaries and suppress estrogen production) ordinarily would have to visit a Penn facility for an injection every month, potentially for years. Now, a nurse can meet patients at home (or before the COVID-19 pandemic, even at their place of work) and administer the injection, saving the patient travel time and associated costs.

This home-based chemotherapy service does not appear to be offered elsewhere in the United States, and a major oncology organization ― the Community Oncology Alliance ― is opposed to the practice because of patient safety concerns.

The service is not offered at a sample of cancer centers queried by Medscape Medical News, including the Dana-Farber Cancer Institute in Boston, the Moffitt Cancer Center in Tampa, the Huntsman Cancer Institute in Salt Lake City, Utah, and Moores Cancer Center, the University of California, San Diego.

Opposition Because of Safety Concerns
On April 9, the Community Oncology Alliance (COA) issued a statement saying it “fundamentally opposes home infusion of chemotherapy, cancer immunotherapy, and cancer treatment supportive drugs because of serious patient safety concerns.”

The COA warned that “many of the side effects caused by cancer treatment can have a rapid, unpredictable onset that places patients in incredible jeopardy and can even be life-threatening.”

In contrast, in a recent communication related to COVID-19, the National Comprehensive Cancer Network tacitly endorsed the concept, stating that a number of chemotherapies may potentially be administered at home, but it did not include guidelines for doing so.

The American Society of Clinical Oncology said that chemotherapy at home is “an issue [we] are monitoring closely,” according to a spokesperson.

What’s Involved
Criteria for home-based chemotherapy at Penn include use of anticancer therapies that a patient has previously tolerated and low toxicity (that can be readily managed in the home setting). In addition, patients must be capable of following a med chart.

The chemotherapy is reconstituted at a Penn facility in a Philadelphia suburb. A courier then delivers the drug to the patient’s home, where it is administered by an oncology-trained nurse. Drugs must be stable for at least a few hours to qualify for the program.

The Penn program started with two regimens: EPOCH (etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone) for lymphoma, and leuprolide acetate injections for either breast or prostate cancer.

The two treatments are polar opposites in terms of complexity, common usage, and time required, which was intended, said Laughlin.

Time to deliver the chemo varies from a matter of minutes with leuprolide to more than 2 hours for rituximab, a lymphoma drug that may be added to EPOCH.

The current list of at-home chemo agents in the Penn program also includes bortezomib, lanreotide, zoledronic acid, and denosumab. Soon to come are rituximab and pembrolizumab for lung cancer and head and neck cancer.

Already Practiced in Some European Countries
Home-based chemotherapy dates from at least the 1980s in the medical literature and is practiced in some European countries.

Gabapentin shows efficacy as opioid alternative for patients with head and neck cancer

Source: www.healio.com
Author: Jennifer Byrne

For many patients with head and neck cancer, treatment-associated oral mucositis is a source of severe pain. Managing this pain is a priority for physicians and interdisciplinary care teams.

Although opioid painkillers historically have been used for this purpose, researchers at Roswell Park Comprehensive Cancer Center investigated the use of gabapentin, a drug used to alleviate nerve pain, as an alternative to narcotics for this patient population.

“Virtually all patients will require some type of pain relief or analgesic medication during the course of chemotherapy and radiation,” study author Anurag K. Singh, MD, professor of oncology and director of radiation research at Roswell Park, told Healio. “We’ve been studying better ways to improve pain control in this population because standard narcotics just don’t work that well. Patients tend to use a lot and they still experience pain, but they are sleepier.”

A dose-dependent effect
In their study, published in Cancer, Singh and colleagues randomly assigned 60 patients with head and neck squamous cell carcinoma to one of two treatment regimens: high-dose gabapentin (2,700 mg daily), progressing sequentially to hydrocodone-acetaminophen and fentanyl when needed (n = 31), or low-dose gabapentin (900 mg daily) progressing to methadone as needed (n = 29).

Safety and toxicity served as the study’s primary endpoints. Pain, opioid requirement and quality of life served as secondary endpoints.

Results showed no difference in pain between the treatment groups, but more patients in the high-dose gabapentin group did not need an opioid while receiving treatment (42% vs. 7%; P = .002). Patients whose treatment progressed to methadone rather than hydrocodone and fentanyl had significantly better quality-of-life outcomes in terms of general health (P = .05), physical functioning (P = .04) role functioning (P = .01) and social functioning (P = .01).

“The bottom line is there was a dose-dependent effect of gabapentin,” Singh told Healio. “When you go from 7% in the lower-dose arm, or 0% if you weren’t giving gabapentin at all, to 42% in the higher-dose arm, that’s a really obvious difference.”

‘Potential arrow in our quiver’
The team at Roswell Park has begun using gabapentin as a first-line approach to pain for patients with head and neck cancer, Singh said.

“We use even higher-dose gabapentin now. We go up to 3,600 mg and follow it with methadone when needed,” he told Healio. “We’re having excellent results. Currently, we’re studying whether we can add something to the gabapentin to get narcotics even further out of the equation.”

Singh and study first author Gregory Hermann, MD, MPH, resident physician in radiation medicine at Roswell Park, have started to evaluate use of the antidepressant venlafaxine (Effexor, Pfizer), which was shown in a study conducted in Europe to enhance the effects of gabapentin.

“Venlafaxine is an SNRI [serotonin-norepinephrine reuptake inhibitor] that is similar to other drugs like duloxetine (Cymbalta, Eli Lilly) that have been used for neuropathic pain in diabetes. It’s a very common medication that is used in primary care,” Hermann told Healio. “At the end of the study, we’ll be able to say whether 3,600 mg is more effective than 2,700 mg and whether venlafaxine adds anything.”

Although opioid painkillers are known for their addictive potential, opioid abuse is less likely among patients with head and neck cancer, provided they are used properly, according to Heath Skinner, MD, PhD, associate professor of radiation oncology at UPMC Hillman Cancer Center. improve significantly within a few weeks of treatment completion,” Skinner told Healio. “In that situation, the goal is to manage pain to allow for eating and drinking as much as possible. Once the acute event leading to the pain is at least partially resolved, we start to wean those medications down. So, in the acute setting, I think these medications have a very limited addiction potential.”

However, if improperly prescribed for long-term use, opioid painkillers could become addictive, Skinner said. Moreover, narcotic painkillers are associated with significant toxicities for an already sick population.

“Constipation is a common effect with opioids and can be particularly challenging for [patients with head and neck cancer] because they’re not drinking a lot of fluids or eating much food,” Skinner told Healio. “That could exacerbate a problem known to happen with narcotic-based pain medications.”

Skinner said gabapentin is a promising alternative to opioids that is readily accessible to clinicians.

“It’s available in the setting of pain control and easily prescribed,” he said. “It’s not something that’s proprietary that a clinician couldn’t acquire. It’s nice to have another potential arrow in our quiver.” – by Jennifer Byrne

Reference:
Hermann GM, et al. Cancer. 2020;doi:10.1002/cncr.32676,

Survivorship clinic helps patients with what comes after head and neck cancer

Source: www.pittwire.pitt.edu/
Author: Gavin Jenkins, excerpted from the fall 2019 issue of Pitt Med magazine

Jonas Johnson presses his hand on Edward Christopher’s neck. The examination room at the UPMC Head and Neck Cancer Survivorship Clinic is chilly on this June morning as Johnson, chair of the University of Pittsburgh Department of Otolaryngology, glides his fingers along the left side of Christopher’s throat.

“Your skin is stiff,” Johnson says. “Scar tissue doesn’t go away.”

Five years ago, Christopher was diagnosed with human papillomavirus (HPV) positive cancer on the base of his tongue, left tonsil and the lymph nodes on the left side of his neck. After undergoing surgery to remove the tumors, he received radiation treatment and chemotherapy, followed by another procedure to remove his lymph nodes.

When he completed the treatment, he posted a picture on Facebook holding a sign that read “cancer free!” That night, he and his family celebrated with dinner at an Italian restaurant. Christopher felt lucky to be alive and grateful to Pitt doctors. He had no idea how difficult the years to come would be. He credits Marci Lee Nilsen, a nurse who is an assistant professor in Pitt’s School of Nursing, with opening his eyes.

In 2016, Johnson and Nilsen created the Survivorship Clinic to help patients like Christopher improve their quality of life after beating head and neck cancer. Most patients grapple with dysphagia—difficulty swallowing—and trismus, commonly known as lockjaw. They might experience a loss of taste, tooth decay, dry mouth and mouth sores. The side effects from radiation and chemotherapy can often cause patients to struggle to talk, hear and sleep, as well. The combination of these treatments with surgery can also lead to mobility issues; many patients end up on disability. Insomnia and sleep apnea can exacerbate anxiety and depression, which also are common issues.

Getting care for these conditions can place a financial strain on patients who have already spent tens of thousands of dollars to overcome cancer.

Survivorship clinics for head and neck cancer are sprouting up across the country. Some of those clinics have more than a few specialists. UPMC’s clinic patients see an otolaryngologist, audiologist, dentist, speech pathologist and physical therapist in one day. And unlike any other survivorship clinic in the United States, they are charged just one co-pay.

The Survivorship Clinic also sets itself apart by how it monitors patients from the start. Nilsen and Johnson meet with patients before they receive radiation and chemotherapy, and then again a month after treatment is completed. After that, patients visit the clinic at least once a year, and depending on their needs, Johnson and Nilsen will coordinate with the appropriate primary care physician, dentist or physical therapist.

Historically, the struggles of head and neck cancer survivors have been approached as an afterthought by many hospitals and primary care physicians. That’s changing as providers recognize the fallout from treatments, which can be lifesaving but also life hobbling. Johnson and Nilsen have seen more than a thousand patients in their three years at UPMC’s Survivorship Clinic. Their work has highlighted the importance of long-term care.

For Johnson, a renowned head and neck cancer surgeon who has been with Pitt since 1977, the Survivorship Clinic represents a new chapter in his career.

“I’ve reinvented myself,” he says. “I say to my residents: Don’t think I’ve repudiated the last 40 years of my career. I still believe in surgery. But I’ve embraced the notion that we must recognize the trouble we cause (treating cancer), and we have to help people with it.”

There’s more to this story. Continue reading about Johnson and Nilsen’s partnership and more patients benefiting from their work.

2019-11-19T14:11:06-07:00November, 2019|Oral Cancer News|
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