HPV Plays Growing Role in Evaluating Therapies

Barbara A. Burtness, MD

Chief, Head and Neck Medical Oncology Co-Leader, Developmental Therapeutics Fox Chase Cancer Center

Philadelphia, PA

With oncologists placing a greater emphasis on the role of the human papillomavirus (HPV) in the progression of head and neck cancers, researchers are dissecting new studies regarding targeted therapies as well as combined therapeutic approaches more thoroughly than ever, especially in light of encouraging new data regarding a more comprehensive approach in treating these patients.

“There has been a progressive move to more intensive therapy over the years, and there has been some sense that we’ve improved outcomes by using these more intensive approaches,” said Barbara A. Burtness, MD, in an interview during the 7th Annual Multidisciplinary Symposium on Head and Neck Cancer, held November 19 in Philadelphia, Pennsylvania.

Burtness, who served as a program director for the conference, made her presentation on state-of the-art therapy for locally advanced head and neck cancer.

Burtness noted that the results of studies that analyze more intensive care should be evaluated carefully, particularly because patients who test positive for HPV tend to have different outcomes than those who test negative for the virus, and there are subtypes within HPV that seem to exhibit different responses to therapies.

Such complexities are illustrated in trials involving cetuximab (Erbitux), a chimeric monoclonal antibody that inhibits epidermal growth factor receptor. In November, the FDA expanded the indications for cetuximab to include the treatment of patients with metastatic head and neck cancers in combination with chemotherapy after trial results showed a dramatic increase in median overall survival.

In the Radiation Therapy Oncology Group’s 0522 trial, investigators theorized that since the addition of cetuximab to platinum-containing regimens improves overall survival, the agent might also enhance survival if added to a regimen of radiation and cisplatin as front-line therapy. The study involved 940 patients who received radiation therapy plus cisplatin with or without cetuximab.

When preliminary results were first reported in June, the study showed that 64.3% of the cisplatinonly group achieved progression-free survival at 2 years, compared with 63.4% of patients who had also received cetuximab. Conversely, the cetuximab group achieved 82.6% overall survival after 2 years, compared with 79.7% of patients who did not receive cetuximab. (J Clin Oncol. 2011;29 [suppl;abstr 5500]).

Burtness noted that even though the trial enrolled more than 900 patients, the study was only statistically powered to 85%. Furthermore, the median follow-up time was 2.4 years, but Burtness said that some of those patients had been followed up for only a few weeks when the results were released.

“Even when final reporting is complete, we will have to bear in mind that this was a very ambitious study of moderate power only,” Burtness said.

Burtness said the results of such trials should be closely studied in terms of HPV involvement. Patients with HPV who also test positive for alterations in the p16 gene, which expresses a tumor suppressor protein, might have different results than patients who are HPV-positive but test negative for p16 mutations. In further analysis of RTOG 0522 results, patients who received cetuximab who were also p16-negative had a lower hazard ratio than those who were p16-positive.