Chemoradiotherapy superior to panitumumab-radiotherapy combination

Issue: November 10, 2012

Chemoradiotherapy conferred better locoregional control rates than panitumumab plus radiotherapy in a cohort of patients with locally advanced squamous cell carcinoma of the head and neck, according to results of the CONCERT-2 study.

Perspective from Barbara Burtness, MD

Researchers conducted the randomized, open-label phase 2 study to evaluate the efficacy of panitumumab (Vectibix, Amgen), a monoclonal antibody against epidermal growth factor receptor.

The researchers enrolled 151 patients with previously untreated, locally advanced, stage III, IVA or IVB squamous cell carcinoma of the head and neck.

The researchers assigned 90 patients to panitumumab plus radiotherapy, and they assigned 61 patients to chemoradiotherapy.

The patients had a median age of 58 years.

Patients in the panitumumab arm underwent three cycles at a dose of 9 mg/kg. Each cycle was administered with accelerated fractionation radiotherapy (XRT). Patients assigned to chemoradiotherapy underwent two cycles of cisplatin (100 mg/m² during XRT).

Locoregional control served as the primary endpoint. Secondary endpoints included PFS, OS and safety.

At 2 years, the locoregional control rate was 61% among patients assigned to chemoradiotherapy compared with 51% for patients assigned to panitumumab plus radiotherapy.

Outcomes for PFS (HR=1.73; 95% CI, 1.07-2.81) and OS (HR=1.59; 95% CI, 0.91-2.79) favored the chemoradiotherapy group.

Dose intensity was high for both groups, according to researchers. Median dose intensity was 100% for panitumumab and 99% for cisplatin, while median XRT dose was 100% in both arms, the researchers wrote.

Grade-3 or higher adverse events occurred in 85% of patients assigned to panitumumab plus radiotherapy and 81% of patients assigned to chemoradiotherapy.

Grade-3 or higher skin disorders occurred more frequently among patients assigned to panitumumab plus radiotherapy (35% vs. 3%). Patients assigned to chemoradiotherapy more frequently reported grade-3 or higher neutropenia (13% vs. 0%) and febrile neutropenia (8% vs. 0%).

For more information:

Giralt J. Abstract #1016O. Presented at: European Society for Medical Oncology; Sept. 28-Oct. 2, 2012; Vienna.

Disclosure: The researchers report advisory board positions and employment relationships with Amgen.

Perspective

Barbara Burtness, MD

This trial was a randomized phase 2 study that compared radiation plus cisplatin with radiation plus panitumumab, a humanized anti-EGFR antibody. This is the first random assignment trial of radiosensitization with an EGFR inhibitor compared directly with radiosensitization with cisplatin. Retrospective studies comparing the two approaches are difficult to interpret because cisplatin is withheld from patients with greater co-morbidity, making it more likely that these are the patients treated with cetuximab/radiation off study. Preliminary reports of R0522 did not demonstrate that the administration of cetuximab on top of chemoradiation improved outcomes. Thus, the results of this trial have been awaited with some interest, not withstanding its relatively small size and the use of panitumumab — for which no evidence of a survival benefit has been shown in head and neck cancers — rather than cetuximab (Erbitux; Bristol-Myers Squib, Eli Lily).

Surprisingly, the study showed a significant decrement in outcome for the patients treated with panitumumab rather than cisplatin. The study may not be large enough to permit subset analysis to discern whether panitumumab was inferior only in patients with the most advanced nodal disease, in whom control of distant micrometastases is a potentially important effect of the cisplatin, in addition to its radiosensitizing properties. The ongoing RTOG trial R1016 compares cisplatin/radiation to cetuximab/radiation in favorable prognosis, p16-positive oropharynx cancers. This large trial focuses on toxicity sparing for a group with good survival, and it utilizes an antibody with proven impact on survival in head and neck cancers. In the meantime, cisplatin plus radiation remains an appropriate standard for those patients fit enough to receive cisplatin.

Barbara Burtness, MD

HemOnc Today Editorial Board member

Disclosures: Burtness reports no relevant financial disclosures.

European Society for Medical Oncology Congress

Chemoradiotherapy superior to panitumumab-radiotherapy combination

Perspective