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James Melotek, MD, discusses two clinical trials looking at the impact of cetuximab in patients with squamous cell carcinoma of the head and neck.
James Melotek, MD
Since its first FDA approval in squamous cell carcinoma of the head and neck (SCCHN) in 2006, cetuximab (Erbitux) has helped oncologists make significant strides in treating patients with the disease.
The EGFR inhibitor is currently approved for the treatment of head and neck cancer as initial treatment of locally or regionally advanced SCCHN in combination with radiation therapy, as first-line treatment of recurrent locoregional disease or metastatic SCCHN in combination with platinum-based therapy with 5-FU, and as a single agent for recurrent or metastatic SCCHN for which prior platinum-based therapy has failed.
A recent randomized phase II study, which was presented at the 2016 Multidisciplinary Head and Neck Cancer Symposium, investigated the addition of cetuximab to induction chemotherapy and hyperfractionated or accelerated chemoradiation therapy (CRT).1
Of the 103 patients included in the trial, 56 were HPV-negative. Those patients were randomized to receive 2 different chemoradiotherapy regimens—either concurrent cetuximab, 5-FU, hydroxyurea, and 1.5 Gy twice-daily radiotherapy (RT) every other week to 75 Gy, or cetuximab, cisplatin, and accelerated RT with delayed concomitant boost to 72 Gy in 42 fractions. Both arms received 2 cycles of weekly induction chemotherapy.
The overall survival (OS) of the entire cohort was 80.3% (95% CI, 73.1%-88.3%) at 5 years. For the HPV-negative subset, OS was 72.5% (95% CI, 61.6%-85.4%). Progression-free survival (PFS) at 5 years was 74.1% (95% CI, 66.3%-82.9%) for the entire cohort and 65.9% (95% CI 54.6%-79.6%) for the HPV-negative group.
No significant difference was found in OS (P = .43) or PFS (P = .57) between the 2 HPV-negative treatment arms after a median follow-up of 68 months.
Cetuximab is also being investigated in the RTOG 1216 trial (NCT01810913), a randomized phase II/III study of surgery and postoperative RT given with concurrent cisplatin versus docetaxel alone versus docetaxel and cetuximab in high-risk SCCHN. Disease-free survival (DFS) is the primary endpoint in the phase II portion, while OS is the primary endpoint in the phase III part of the ongoing study.
To learn more about the impact of both trials and the role of cetuximab in SCCHN, OncLive spoke with James Melotek, MD, a radiation oncology resident at the University of Chicago Medicine and the lead study on the phase II trial presented at the symposium.Melotek: This was a phase II randomized trial that investigated 2 endpoints. The primary endpoint of this trial was to invest the addition of cetuximab to both induction chemotherapy and chemoradiotherapy, and compare our results with a historical control.
The secondary endpoint of this trial was to investigate 2 chemoradiotherapy platforms; Cetux-FHX, which consists of cetuximab, 5-FU, hydroxyurea with concomitant twice-daily radiotherapy versus Cetux-PX, which consists of cetuximab, cisplatin, and accelerated radiotherapy with delayed concomitant boost.
Based on these findings, what role could cetuximab play in the treatment landscape for this disease?
What we found is that both subgroups performed far superior beyond the historical control. In particular, the HPV-negative subgroup did very well, perhaps due to the intensity of the treatment. With respect to the two chemoradiotherapy platforms there were no significant differences in survival outcomes, according to the platform treated.Currently, the role of cetuximab in locally advanced head and neck cancer is undetermined. We know that it increases survival when added to radiotherapy in the single modality setting, and that it increases survival when added to cytotoxic chemotherapy in the metastatic setting.
The question that still remains is, “How do we incorporate cetuximab best into locally advanced head and neck cancer?” One potential outcome of this trial is that these poor prognosis patients did particularly well, so it is possible that the integration of cetuximab into induction chemotherapy may have a potential role for the intensification of treatment in poor prognosis subgroups.
What are the next steps regarding the investigation of cetuximab in head and neck cancer?
It is also possible that there is a degree of activity between cetuximab and taxanes and perhaps cetuximab in combination with docetaxel, which is currently being investigated in the RTOG 1216 trial, is another option in the future.The RTOG 1216 trial is a very interesting study. It is investigating the role of cetuximab with taxanes and the results of that will be interesting. There was a presentation that showed that, in an earlier trial by the RTOG, there was a decrease in distant metastasis with the concurrent use of cetuximab with taxanes—despite the use of only radiosensitizing doses of taxane in the trial. It will be interesting to see what the results of RTOG 1216 are, with respect to the role of cetuximab and taxanes.Cetuximab cannot be recommended with concurrent cisplatin chemoradiotherapy, based on the RTOG trial. However, the use of cetuximab concurrent with other chemotherapy agents, such as a taxane, is certainly an option that will be investigated, especially with patients who are not candidates for platinum-based chemotherapy.
Melotek JM, Haraf DJ, Blair EA, et al. Final results of a randomized phase 2 trial investigating the addition of cetuximab to induction chemotherapy and accelerated or hyperfractionated chemoradiation therapy for locoregionally advanced head and neck cancer: HPV-negative subset analysis. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; Feb 18-20, 2016; Scottsdale, AZ. Abstract 7.