Panitumumab Extends Progression-Free Survival in HPV-Negative Subset of Advanced Head and Neck Cancer

Stockholm, Sweden—The addition of panitumumab to chemotherapy improved overall survival (OS) and progression-free survival (PFS) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck that were negative for the human papillomavirus (HPV), but no benefit was shown for HPV-positive tumors.

These results were presented in a subanalysis of the European SPECTRUM trial presented as a late-breaking abstract at 2011 European Multidisciplinary Cancer Congress (ECCO, ESMO, ESTRO).

The main results of SPECTRUM were reported at ESMO 2010, showing that patients who received panitumumab plus chemotherapy, versus chemotherapy alone, had a significant improvement in PFS but not OS.

The current sub-analysis is the first report of treatment outcomes related to HPV status with any drug in the first-line treatment of advanced squamous cell head and neck cancer, according to lead investigator Jan Vermorken, MD of Antwerp University Hospital in Belgium.

SPECTRUM evaluated panitumumab, a monoclonal antibody targeting the epidermal growth factor receptor (EGFR), plus platinum-based chemotherapy (cisplatin + 5-FU) in 657 patients with recurrent or metastatic disease. Three hundred seventy-seven (57%) had samples evaluable for HPV status, of which 22% were HPV-positive (ie, had staining in at least 10% of cells), and 78% were HPV-negative.

PFS and OS Improved in HPV-Negative Subset Only

Median OS, in the HPV-negative subset, was 11.8 months in the panitumumab/chemotherapy arm versus 8.6 months in the chemotherapy arm, for a 27% statistically significant reduction in the risk of death (P = 0.02). In contrast, in the HPV-positive subset, the addition of panitumumab was not associated with a survival benefit: median OS was 10.9 months with panitumumab/chemotherapy versus 12.1 months with chemotherapy alone (P = 0.88), Vermorken reported.

“The survival was strikingly and significantly different in the HPV-negative patients who received panitumumab, and this was not the case in the HPV-positive patients,” he noted. The test for interaction, however, was not significant (P = 0.332), possibly due to small numbers of patients in the HPV-negative group, he added.

Progression-free survival was also significantly, though not as strikingly, improved with panitumumab in the HPV-negative subset, where median PFS was 6.5 months with panitumumab/chemotherapy versus 5.1 months with chemotherapy alone (P = .002). In the HPV-positive subset, median PFS was 5.5 and 5.3 months, respectively. Again, the test for interaction was not significant (P = .097).

The effect of panitumumab in HPV-negative patients was consistent across all subsets, including patients with poor performance status and those with prior platinum chemotherapy. Adverse events in the panitumumab arm were as expected, with serious adverse events leading to study or drug discontinuation seen in 14% of the panitumumab arm and 12% of the chemotherapy-alone arm.

In the overall population, he added, there was a trend for a more favorable outcome in patients with HPV-positive disease; however, “this should be confirmed in an independent dataset,” he said.

“Although our data suggest that it may be worthwhile to use HPV status for stratification in future phase III trials with anti-EGFR treatment in recurrent/metastatic squamous cell carcinoma of the head and neck, it remains speculative and confirmation is first needed,” Dr. Vermorken said.

Jean Bourhis, MD, PhD, of the Institute Gustave Roussy, Villejuif, France, discussed the presentation, noting that HPV has become a major prognostic factor in locally advanced head and neck cancer (especially of the oropharynx); however, its prognostic value in recurrent and metastatic disease is unknown.

“The role of HPV in recurrent and metastatic disease for predicting response to EGFR monoclonal antibodies is also unknown,” he noted.

But the value of targeting EGFR with EGFR inhibitors, especially cetuximab, has been established, he said. “The amount of benefit in PFS is significant, and there is also a survival benefit for the first time in 30 years,” he said.

The SPECTRUM trial had a relatively similar design to the pivotal cetuximab trial, and it also demonstrated a significant PFS benefit but not an OS benefit, which was the primary endpoint, he noted. He also noted that in a phase II trial (unpublished) lapatinib, another EGFR inhibitor, has shown benefit in locally advanced disease.

“There are some clear limitations of the study,” according to Bourhis. It is a subgroup and retrospective analysis, only two thirds of the patients had HPV status evaluable, the analysis of HPV status was primarily performed on the primary tumor, and the test for interaction was nonsignificant.

Nevertheless, this is the first description of EGFR inhibition activity specifically in HPV-negative disease, and the data are consistent with previous findings.

“There is a potentially important clinical impact of these findings,” he commented. “But because of some limitations in the study there is a need for confirmation and for generating additional evidence-based medicine (level 1) in recurrent/metastatic disease.”