Head, Neck, and Non-Colorectal GI Cancers at ASCO 2012: Coverage with Commentary by Dr. Barbara Burtness
Dr. Barbara Burtness, MD
In the world of cancer, head and neck cancers are probably the most diverse category, comprising oral cancer, oropharyngeal cancer, throat cancer, and more. When trying to put a “face” on this diverse group, I think of the well-known actor Michael Douglas, who is in remission with his throat cancer. Other famous individuals who have died from a dreaded cancer type within this category include Sammy Davis, Jr., Babe Ruth, and Sigmund Freud. The overall incidence of head and neck cancers in the United States is approximately 15 per 100,000 persons.1
Medical oncologists who treat head and neck cancers might also be cross-trained in the treatment of noncolorectal gastrointestinal cancers, which include esophageal and esophagogastric cancers. More common in males than females, the incidence of esophageal and esophagogastric cancer is 7.8 per 100,000 men and 1.8 per 100,000 women.2
Head and neck cancers and noncolorectal GI cancers were covered in several sections at ASCO 2012. This article will highlight three abstracts in these areas. In the first of these oral abstracts, entitled “A randomized multicenter trial of epirubicin, oxaliplatin, and capecitabine (EOC) plus panitumumab in advanced esophagogastric cancer (REAL3),” the investigators aimed to evaluate the addition of the anti-EGFR antibody panitumumab (P) to EOC in patients with advanced esophagogastric cancer.3 Patients were randomized to receive EOC (E 50mg/m2, O 130mg/m2, C 1250mg/m2/day) or mEOC plus P (E 50mg/m2, O 100mg/m2, C 1000mg/m2/day, P 9mg/kg). Patients were then followed until they reached the primary end point: overall survival (OS); secondary end points included progression-free survival (PFS), response rate (RR), toxicity, and biomarker evaluation.
The trial met its primary end point, with a median OSEOC of 11.3 months compared to 8.8 months with mEOC plus P (HR 1.37: 95% CI 1.07–1.76, P=0.013). These results were concordant with a median PFS of 7.4 and 6.0 months, for EOC and mEOC plus P, respectively (HR 1.22: 95% CI 0.98–1.52, P=0.068). Response rates were 42% and 46% for EOC and mEOC plus P, respectively (odds ratio 1.16: 95% CI 0.81–1.57, P=0.467). In terms of adverse events, treatment with mEOC plus P was associated with increased grade 3/4 diarrhea (17% vs 11%), skin rash (14% vs 1%) and thrombotic events (12% vs 7%), but decreased hematological toxicity (14% vs 31).
“At one of the interim analyses, investigators had to close the trial because there was an increased hazard of death in the patients in the experimental arm,” said Barbara Burtness, MD, Fox Chase Cancer Center, Philadelphia, PA. “In response, investigators took all of the patients that were still in the panitumumab arm and crossed them over into the other arm…despite that, at this point, the hazard for death was still high.” According to Dr. Burtness, the following issues could have produced this outcome. The worst outcome is most likely explained by the reduction in the doses of the conventional chemotherapeutic drugs known to be effective in esophagogastric cancer. The response rate was just as high in the modified arm and the PFS was not nearly as divergent as the OS, thus raising the possibility of an unknown post-progression event that might have impacted survival. “This event could be related to toxicity or disease progression after panitumumab therapy was terminated, but the exact reason is difficult to discern,” said Dr. Burtness.