CONCERTed View is Panitumumab Should Not Adjunct, Replace Chemoradiotherapy in SCCHN

Phase II trial results do not support the use of panitumumab as an adjunct to or substitute for cisplatin in combination chemoradiotherapy in patients with squamous-cell carcinoma of the head and neck

medwireNews: Results of the CONCERT-1 and -2 trials suggest that patients with locally advanced squamous-cell carcinoma of the head and neck (SCCHN) do not benefit from being given panitumumab as an adjunct to or replacement for cisplatin-based chemoradiotherapy.

In both trials, the panitumumab group fared worse in terms of the primary and secondary endpoints compared with the control group, calling into question the role of Epidermal growth factor receptor inhibition in this patient population, the two groups of researchers report.

Final analyses of the open-label, phase II CONCERT-1 and -2 trials, of treatment-naïve patients with stage III, IVa or IVb SCCHN are reported in The Lancet Oncology.

In CONCERT-1, patients were randomly assigned to receive either three cycles of panitumumab 9 mg/kg every 3 weeks plus cisplatin at a dose of 75 mg/m2 or three cycles of cisplatin 100 mg/m2. All patients were given standard fractionation radiation at doses of 70 Gy and 50 Gy for gross tumour and areas at risk of subclinical disease, respectively.

Sixty-one percent of the 87 patients who received panitumumab plus chemoradiotherapy achieved local-regional control at 2 years from treatment initiation, as did a comparable 68% of the 63 patients given chemoradiotherapy alone.

At 2 years, progression-free survival (PFS) and overall survival (OS) rates were 61% and 69%, respectively, in the panitumumab plus chemoradiotherapy group, and 65% and 78%, respectively, in the chemoradiotherapy group.

Kaplan Meier analysis confirmed there was no significant difference in the three outcomes between the two treatment groups, although panitumumab was associated with a significantly higher rate of serious adverse events.

Researcher Ricard Mesía, from Institut Català d’Oncologia in Barcelona, Spain, and team speculate that the lower cisplatin dose and more radiotherapy interruptions may have negatively affected the outcomes in the panitumumab plus chemoradiotherapy group.

Participants in the CONCERT-2 trial were randomly assigned to receive three cycles of panitumumab 9 mg/kg every 3 weeks or two cycles of cisplatin 100 mg/m2, alongside 70 to 72 Gy accelerated fractionation radiotherapy for gross tumour and 54 Gy for areas of subclinical disease.

Of the 89 individuals who received panitumumab plus radiotherapy and the 61 chemoradiotherapy-treated patients, 51% and 61%, respectively, achieved local-regional control at 2 years, a non-significant difference.

Moreover, after 2 years patients given panitumumab had a significantly lower PFS rate and a trend towards a lower OS rate than those given cisplatin, at 41% versus 62% and 63% versus 71%, respectively, report Jordi Giralt, from Hospital Vall d’Hebron in Barcelona, Spain.

CONCERT-2 also found that incorporation of panitumumab “seemed to increase toxicity”, the researchers say. Mucosal inflammation, dysphasia and radiation skin injury were the most common grade 3 or 4 adverse events in both trials, with each occurring more frequently in the panitumumab than the control group.

The two trials were exploratory in design, a point noted by Vassiliki Saloura and Everett Vokes, from University of Chicago in Illinois, USA, in a linked commentary.

“Nevertheless, the consistency of their results and absence of a positive outcomes signal do provide guidance with respect to the future use of panitumumab in the curative-intent setting and reconfirm chemoradiotherapy as the primary standard care option”, the authors say.

References

Mesía R, Henke M, Fortin A, et al. Chemoradiotherapy with or without panitumumab in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-1): a randomised, controlled, open-label phase 2 trial. Lancet Oncol; Advance online publication 15 January 2015. doi:10.1016/S1470-2045(14)71198-2

Giralt J, Trigo J, Nuyts S, et al. Panitumumab plus radiotherapy versus chemoradiotherapy in patients with unresected, locally advanced squamous-cell carcinoma of the head and neck (CONCERT-2): a randomised, controlled, open-label phase 2 trial. Lancet Oncol; Advance online publication 15 January 2015. doi: 10.1016/S1470-2045(14)71200-8

Saloura V, Vokes EE. EGFR-based bioradiotherapy in SCCHN. Lancet Oncol; Advance online publication 15 January 2015. doi:10.1016/S1470-2045(15)70006-9

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