Investigational anticancer drug may benefit subgroup of patients with head and neck cancer

April 8, 2014, American Association for Cancer Research

Patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), the most common form of head and neck cancer, may benefit from treatment with the investigational drug dacomitinib if their cancer has no defects in a cell signaling pathway called the PI3K pathway and no signs of excessive inflammation, according to results of a phase II clinical trial presented here at the AACR Annual Meeting 2014, April 5-9.

"Patients with recurrent and/or metastatic SCCHN have a very poor prognosis. There are few approved therapies for these patients and their median survival is six to nine months," said Byoung Chul Cho, M.D., Ph.D., an associate professor at Yonsei Cancer Center in Seoul, the Republic of Korea. "Our data show that dacomitinib has promising antitumor activity in heavily treated recurrent and/or metastatic SCCHN in patients without PI3K pathway alteration or overexpression of proinflammatory cytokines.

"Our findings obviously need confirming in phase III clinical trials comparing the efficacy of dacomitinib with other palliative chemotherapy," added Cho. "By using our biomarker data to select those patients who are most likely to benefit from the drug—those without PI3K pathway alteration or overexpression of proinflammatory cytokines—the trial will be more likely to succeed."

Dacomitinib blocks the activity of a protein called epidermal growth factor receptor (EGFR). According to Cho, the rationale for their clinical trial is that most SCCHNs have elevated levels of EGFR, which makes it a potential therapeutic target.

"If our results are confirmed in phase III , dacomitinib could provide a new targeted treatment option for a disease for which new therapies are desperately needed," said Cho. "We are conducting further biomarker analysis to better define patients most likely to respond."

Cho and colleagues enrolled 48 patients with recurrent and/or metastatic SCCHN in their phase II clinical trial. All patients received oral dacomitinib once a day. Response Evaluation Criteria In Solid Tumors (RECIST) guidelines, version 1.1, were used to assess patients' responses.

Ten patients had a partial response and 31 patients had stable disease. This meant that the overall response rate, which was the primary endpoint of the study, was 21 percent. In addition, after a median follow-up of 8.4 months, the average time to disease progression was 3.9 months and the average overall survival time was 6.6 months.

The researchers performed genetic analyses of the patients' tumor samples and identified a number of markers associated with response. Patients with tumors containing mutations in either of two genes important for the PI3K pathway, PIK3CA and PTEN, had their disease progress more than twice as quickly as patients with tumors without PIK3CA or PTEN mutations: Average progression-free survival was 2.9 months and 4.9 months, respectively. For two of the patients with tumors lacking PIK3CA and PTEN mutations, the time to disease progression was much longer than the average, 13.1 and 18.9 months.

The researchers also found differences in average progression-free survival between with tumors with high and low levels of genes linked to inflammation, including IL6, IL8, PTGS2, and PLA2G2A: Average progression-free survival times were 2.8 months and 9.9 months, respectively.

Explore further: Palbociclib shows promising results in patients with hormone receptor-positive metastatic breast cancer

Related Stories

Palbociclib shows promising results in patients with hormone receptor-positive metastatic breast cancer

April 7, 2014
The drug palbociclib, an inhibitor of cyclin-dependent kinases (CDK) 4 and 6, significantly improved progression-free survival when administered as a first-line treatment in patients with hormone receptor-positive, metastatic ...

New drug combination delayed disease progression for subgroup of women with metastatic breast cancer

December 12, 2013
Adding the drug dasatinib to a standard antihormone therapy, letrozole, doubled the time before disease progressed for women with hormone receptor-positive, HER2-negative metastatic breast cancer, according to results of ...

Researchers narrow the search for biomarkers of drug resistance in head and neck cancer patients

May 31, 2013
Researchers from Fox Chase Cancer Center will present data at the 49th Annual Meeting of the American Society of Clinical Oncology on Saturday, June 1, which shows the discovery of potential biomarkers that may be used to ...

New combination therapy fails to delay progression of advanced breast cancer

December 13, 2013
Adding the antibody therapy ramucirumab to the chemotherapy drug docetaxel did not delay disease progression for patients with HER2-negative, advanced breast cancer, according to results of a placebo-controlled, randomized, ...

Investigational drug may increase survival for some patients with advanced melanoma

March 4, 2014
An experimental drug aimed at restoring the immune system's ability to spot and attack cancer halted cancer progression or shrank tumors in patients with advanced melanoma, according to a multisite, early-phase clinical trial ...

Biomarker analysis identified women most likely to benefit from T-DM1

April 7, 2013
For women with metastatic, HER2-positive breast cancer, the amount of HER2 on their tumor might determine how much they benefit from a drug called trastuzumab emtansine (T-DM1), according to data from a subanalysis of the ...

Recommended for you

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.