Merck’s Keytruda shores up head and neck case with first-line trial win

Author: Carly Helfand Source: www.fiercepharma.com Merck’s Keytruda may just be on its way to earlier use in head and neck cancer, an area where it once faced some questions. On Wednesday, the New Jersey drugmaker said that in a phase 3 trial in previously untreated patients, Keytruda topped a standard-of-care regimen that includes Eli Lilly’s Erbitux at extending overall survival in patients with tumors expressing a certain level of biomarker PD-L1. The data came from an interim analysis of the trial that also showed Keytruda hadn’t yet met the study’s other primary endpoint, which measures time to cancer progression. But overall survival is often considered the gold standard in cancer trials, and Merck will be taking the win in that department to regulators worldwide. Right now, Keytruda bears an approval in head and neck cancer but only in patients whose disease has worsened on or after chemo. And after snagging that conditional approval, last July it failed to prove that it could extend the lives of patients in that group. As analysts pointed out at the time, though, that miss was narrow, coming just shy of statistical significance. The FDA kept the approval in place, and now, Merck has the data to back it up. If Merck can win a new indication from the FDA, it could gain access to a patient pool that grows by about 63,000 U.S. cases per year. And that's a group Keytruda's rival, Bristol-Myers Squibb’s Opdivo, can't currently treat: Its approval only extends to previously [...]

Immunotherapies gaining traction in head and neck cancers

Source: www.targetedonc.com Author: Greg Kennelty An explosion of immunotherapies is on the horizon for patients with metastatic head and neck cancer, specifically as phase III trials begin to report findings for PD-1 inhibitors. This upcoming wave of new therapies places importance on understanding optimal treatment settings and adverse events associated with these therapies. In late January, the phase III CheckMate-141 trial investigating the anti–PD-1 agent nivolumab was stopped early, due to a substantial improvement in the primary endpoint of overall survival (OS). The drug was put up against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel following progression on a platinum-based therapy. At this time, data from the study have not yet been released but are being prepared for future presentation. Findings from the study are being discussed with the FDA and other health authorities. In addition to nivolumab, the PD-1 inhibitor pembrolizumab (Keytruda) demonstrated encouraging activity in patients with with advanced PD-L1–positive esophageal carcinoma during the phase Ib KEYNOTE-028 study. Additionally, the agent was effective for patients with squamous cell carcinoma of the head and neck in the phase I KEYNOTE-012 study. In the head and neck cancer population, the objective response rate with pembrolizumab was 24.8% in 117 evaluable patients. Tumor shrinkage was experienced by 56% of patients and another 25% had stable disease. The response rate seen with pembrolizumab was similar, regardless of HPV infection status. In those with HPV-positive disease, the ORR was 20.6% compared with 27.2% in the negative group. To gain further insight, [...]

2016-02-18T14:35:44-07:00February, 2016|Oral Cancer News|

Nivolumab Could Change Head and Neck Cancer Treatment Paradigm

Source: www.Targetedonc.comAuthor: Laura Panjwani "To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer." - Robert Ferris, MD, PhD With the phase III CheckMate-141 trial being stopped early due to the anti–PD-1 agent nivolumab having met its primary endpoint of overall survival improvement in head and neck cancer, Robert Ferris, MD, PhD, couldn't be more elated. "This is what I've devoted my career to, and it is gratifying to see that really come to pass," said Ferris, professor and chief, Division of Head and Neck Surgery, vice chair for Clinical Operations, associate director for Translational Research, and coleader of the Cancer Immunology Program at the University of Pittsburgh Cancer Institute, in an exclusive interview with Targeted Oncology. "To have an anti–PD-1 agent be proven to improve survival in head and neck cancer in a randomized phase III trial, and the potential for a new FDA approval in the near future is a game changer. There is now hope for a lot of patients and physicians who have been frustrated by this difficult-to-treat disease. This opens up a whole new class of therapies for this population." Ferris, who acted as cochair/coprimary investigator for the trial alongside Maura Gillison, MD, PhD, Ohio State University, said the trial pitted nivolumab against the investigator’s choice of cetuximab (Erbitux), methotrexate, or docetaxel in patients with platinum-refractory squamous cell carcinoma [...]

2016-02-16T09:24:23-07:00February, 2016|Oral Cancer News|

Keytruda doubles efficacy of only targeted therapy for head and neck cancer

Source: www.curetoday.com Author: Lauren M. Green The immunotherapy Keytruda (pembrolizumab), in a recent study, proved twice as effective for the treatment of head and neck cancer as Erbitux (cetuximab), the only targeted therapy indicated as a therapy for the disease. The multisite study offers the largest experience to date of how immunotherapy can be deployed in patients with head and neck cancer, and could change the way the disease is treated. The findings were announced May 29 during the annual meeting of the American Society of Clinical Oncology, a gathering of nearly 30,000 oncology professionals taking place in Chicago. Keytruda is an antibody designed to disable the protein PD-1 so it cannot do its job of keeping the immune system in check; this allows T cells to become more active in recognizing and fighting cancer cells. In the study, investigators found that the drug produced broad and durable responses in patients with advanced head and neck cancer. Fifty-six percent of patients in the study experienced some tumor shrinkage with Keytruda, and 86 percent of those patients continued to respond to treatment at data cutoff on March 23, 2015. Keytruda produced an overall response rate (ORR) of 25 percent, and it proved active in both HPV (human papillomavirus)-positive and HPV-negative patients. “The efficacy was remarkable — pembrolizumab seems to be roughly twice as effective, when measured by response, as our only targeted therapy, cetuximab,” said Tanguy Seiwart, an assistant professor of medicine and associate leader of the head and neck cancer [...]

Merck immunotherapy appears effective in head and neck cancer – study | Reuters

Source: www.firstpress.comAuthor: Bill Berkrot  A Merck & Co drug that helps the immune system fight cancer was about twice as effective as the current standard therapy for patients with recurrent or advanced head and neck cancers, according to study data released on Friday. A quarter of the 132 patients who received the drug, Keytruda (pembrolizumab), saw their tumors shrink by at least 30 percent. Fifty-six percent of patients experienced at least some tumor shrinkage in the ongoing single drug Phase I study dubbed Keynote-012, researchers reported. "This is remarkable because we don't usually see this level of activity with new agents. We have a track record of failure," said Dr. Tanguy Seiwert, lead investigator of the study from the University of Chicago. Advanced head and neck cancer is currently treated with Eli Lilly's Erbitux, known chemically as cetuximab, which typically has a response rate of 10 percent to 13 percent. "The only thing that works is cetuximab and this looks at least twice as good," said Seiwert, who was presenting the Keytruda data at the American Society of Clinical Oncology meeting in Chicago. ADVERTISING Merck shares rose more than 1 percent to $60.43 on the New York Stock Exchange. Keytruda and Opdivo from Bristol-Myers Squibb Co are at the forefront of a promising new class of drugs called PD-1 inhibitors that block a mechanism tumors use to evade the immune system. Keytruda is approved to treat advanced melanoma and awaits a decision for use in lung cancer. It is being [...]

Experimental EGFR inhibitor added nothing but rash

Source: www.oncologypractice.com Author: Neil Osterweil, Oncology Report Digital Network The addition of the experimental targeted agent zalutumumab to primary curative chemoradiation for head and neck cancers did not improve locoregional control, disease-specific survival, or overall survival at 3 years of follow-up. The only thing that zalutumumab added to therapy was a skin rash in the large majority of patients who received it, reported Dr. Jens Overgaard, of the department of experimental clinical oncology at Aarhus University, Denmark. Response to zalutumumab, a monoclonal antibody targeted to the epidermal growth factor receptor (EGFR), was not related to tumor human papillomavirus 16 (HPV/p16) status or to chemoradiotherapy, Dr. Overgaard reported at the Multidisciplinary Head and Neck Cancer Symposium. The results of the DAHANCA 19 trial echo those of the RTOG (Radiation Oncology Therapy Group) trial 0522, which found no benefit from the addition of the EGFR inhibitor cetuximab (Erbitux) to accelerated cisplatin-based chemoradiotherapy, said Dr. Paul Harari, an invited discussant from the University of Wisconsin, Madison. "Where I think we have a lot of unanswered questions is acknowledging how little we actually understand about EGFR biology, despite now 40 years of progressive knowledge," Dr. Harari said. "We’re now seeing very clearly in molecular and clinical correlate studies that the more we suppress the EGFR, the more we see collateral overexpression of additional RTKs [receptor tyrosine kinases], including members of the HER family, such as HER-3, that enable an escape mechanism for tumors that become resistant to EGFR inhibition," he said. Dr. Overgaard and [...]

Erbitux add-on falls short in esophageal cancer

Source: www.medpagetoday.com Author: Charles Bankhead, Staff Writer, MedPage Today The addition of a targeted agent to definitive chemoradiation failed to improve survival in an unselected population with esophageal cancer, a randomized trial showed. In fact, patients who received cetuximab (Erbitux) with chemoradiation had significantly worse overall survival (OS) reflected in a 50% increase in the hazard versus chemoradiation alone, reported Thomas Crosby, MD, of Velindre Hospital in Cardiff, Wales, and colleagues. Investigators could not find any subgroup of patients who benefited from cetuximab, they said in a presentation at the Gastrointestinal Cancers Symposium. "The addition of cetuximab cannot be recommended to standard definitive chemoradiotherapy in the treatment of unselected patients with esophageal cancer," Crosby said. "The use of high-quality definitive chemoradiotherapy in the treatment of localized, poor-prognosis esophageal cancer was associated with excellent survival compared with previous radiotherapy and surgical series," he added. Randomized trials have shown that definitive (or primary) chemoradiation improves survival in localized esophageal cancer compared with a single treatment modality. In England, definitive chemoradiation has been used primarily for patients with localized disease that is unsuitable for surgery, Crosby said. Add-on therapy with cetuximab has improved outcomes in other cancers, notably head and neck cancer and colorectal cancer. The findings provided a rationale for evaluating the addition of cetuximab to primary radiation therapy for localized esophageal cancer. Crosby presented results of a randomized trial wherein patients with localized (stage I-III) esophageal cancer (less than 10 cm). Patients were excluded if they had celiac lymph-node involvement. The [...]

Scientists find new way to boost cancer drugs

Source: www.drbicuspid.com Author: DrBicuspid Staff Shutting down a specific pathway in cancer cells appears to improve the ability of common drugs to wipe those cells out, according to new research from scientists at Fox Chase Cancer Center (Cancer Discovery, January 2013, Vol. 3:1, pp. 96-111). The new approach appears to enhance the tumor-killing ability of a commonly prescribed class of drugs that includes cetuximab (Erbitux), used to treat head and neck cancers. These drugs work by blocking the activity of the epidermal growth factor receptor (EGFR), which sits on the cell surface and senses cues from the environment, telling cancer cells to grow and divide, according to co-author Igor Astsaturov, MD, PhD, an attending physician in the department of medical oncology at Fox Chase. In 2010, Dr. Astsaturov and his colleagues identified a pathway in the cell that, when blocked, completely suppressed EGFR activity. Interestingly, the pathway consists of a series of enzymes that, when working in concert, synthesize new molecules of cholesterol. Working with cancer cells in the lab, the researchers inactivated a key gene in the cholesterol synthesis pathway, and found the cells became more vulnerable to treatment with cetuximab. The same was true in mice that lacked this particular pathway, according to Dr. Astsaturov. "Most tumors are only moderately sensitive to inhibitors of EGFR, but when these tumors lack an essential gene in the cholesterol pathway, they become exquisitely sensitive to the anti-EGFR drugs," he said. "The cancers literally melt away in mice." The researchers then removed [...]

Germany’s Merck halts supply of cancer drug to Greek hospitals

Source: Reuters.com Date: November 3, 2012 German pharmaceuticals firm Merck KGaA is no longer delivering cancer drug Erbitux to Greek hospitals, a spokesman said on Saturday, the latest sign of how an economic and budget crisis is hurting frontline public services. Drugmakers raised concerns with EU leaders earlier this year over supplies to the euro zone's crisis-hit southern half and Germany's Biotest in June was the first to stop shipments to Greece because of unpaid bills. Publicly-owned hospitals in some countries worst hit by the euro zone debt crisis had been struggling to pay their bills, Merck's chief financial officer, Matthias Zachert, was quoted as saying by German paper Boersen-Zeitung in an interview on Saturday. He said however that the only country where Merck had stopped deliveries was Greece. "It only affects Greece, where we have been faced with many problems. It's just the one product," he told the paper. A spokesman for the company told Reuters that the drug concerned was Erbitux and that ordinary Greeks can still purchase it from pharmacies. Some countries have taken action to pay bills, such as in Spain, where the government has said it will help hospitals to pay off debts. "That has improved things, even though the situation should still be regarded as critical for the coming years," Zachert said. Erbitux is Merck's second best-selling prescription drug, bringing in sales of 855 million euros ($1.1 billion) in 2011 from treating bowel cancer and head and neck cancer. ($1 = 0.7785 euros) This news story was resourced by the Oral Cancer [...]

2012-11-05T11:16:35-07:00November, 2012|Oral Cancer News|

Facing the facts: HPV-associated head and neck cancers get a second look

Source: www.curetoday.com Author: Charlotte Huff Kevin Pruyne knew he didn’t fit the stereotype of a hard drinker or heavy smoker who one day develops an oral cancer. The 52-year-old mechanic had been working a three-week stint in a remote section of northern Alaska, repairing trucks on an oil field, when he noticed a hard lump beneath his jaw while shaving. For nearly three months, as Pruyne was prescribed antibiotics for a possible infection and then later shuttled between physician specialists, he kept hearing the same thing: the lump could not be cancer. Pruyne only occasionally consumed alcohol and had never smoked. His wife, Kathy, began researching her husband’s symptoms, which included repetitive throat clearing, a nagging sensation that something was lodged in his throat and ringing in his ears. And the lump, which looked like the top half of an egg, felt solid to the touch. This wasn’t some inflamed lymph node from a lingering head cold, Kathy Pruyne says. “He had every symptom [of cancer], but nobody would listen to me.” Pruyne received a diagnosis of stage 4 oral cancer, which started with a tumor at the base of his tongue. He had already begun chemotherapy when he learned that researchers had discovered an association between the human papillomavirus (HPV) and increasing rates of oropharyngeal cancers. He asked that his tissue be tested; the results came back positive. Pruyne says he wanted to know whether his cancer was caused by HPV because “the prognosis is considerably better with HPV-positive cancer.” [...]

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