Investigational drug may benefit head/neck cancer patients

The investigational drug dacomitinib may benefit patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), according to a clinical trial by researchers from South Korea. This is the most common form of head and neck cancer.

"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, MD, PhD, an associate professor at the Yonsei Cancer Center in Seoul, South Korea, in a press release. The researchers presented their findings at the recent American Association for Cancer Research meeting in San Diego. "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."

Byoung Chul Cho, MD, PhD. Image courtesy of the American Association for Cancer Research.

Dacomitinib showed positive results in their phase II clinical trial, but Dr. Cho noted the drug's benefits need to be confirmed in phase III trials that compare its efficacy with other palliative chemotherapy.

"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," Dr. Cho said.

Dacomitinib blocks the activity of a protein called epidermal growth factor receptor (EGFR). According to Dr. 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 clinical trials, dacomitinib could provide a new targeted treatment option for a disease for which new therapies are desperately needed," Dr. Cho said. "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.

Ten patients had a partial response, and 31 patients had stable disease. This meant that the overall response rate, which was the primary end point of the study, was 21%. 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 patients 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.

And another drug, afatinib, is slated for tests on patients with head and neck squamous cell carcinoma who have received definitive chemoradiotherapy. The Dana-Farber Cancer Institute is recruiting such patients for a phase III trial to compare the efficacy and safety of afatinib with a placebo as adjuvant therapy.

Pfizer, which makes dacomitinib, announced in January that results from two randomized phase III studies of dacomitinib in patients with advanced non-small cell lung cancer did not demonstrate statistically significant improvement in progression-free survival when compared with the EGFR inhibitor erlotinib.

And in an ongoing phase III trial, ARCHER 1050, is evaluating progression-free survival of dacomitinib in a different patient population than was studied in the prior two trials. The trial compares dacomitinib versus gefitinib in patients who had no prior treatment with EGFR-mutant advanced non-small cell lung cancer. The results are expected in 2015.