ESMO 2018: Cetuximab vs Cisplatin in Patients With HPV-Positive Oropharyngeal Cancer Receiving Radiotherapy
Patients with human papillomavirus (HPV)-positive throat cancer responded better to chemoradiotherapy than to cetuximab (Erbitux) with radiotherapy, according to late-breaking research reported by Mehanna et al at the European Society for Medical Oncology (ESMO) 2018 Congress (Abstract LBA9_PR).
“Many patients have been receiving cetuximab with radiotherapy on the assumption that it was as effective as chemotherapy with radiotherapy and caused less side effects, but there has been no head-to-head comparison of the two treatments,” said study author Hisham Mehanna, PhD, BMedSc, MBChB, FRCS, FRCS(ORL-HNS), Chair, Head and Neck Surgery, Institute of Cancer and Genomic Sciences, University of Birmingham.
HPV-positive throat cancer responds well to a combination of cisplatin chemotherapy and radiotherapy, and patients can survive for 30 to 40 years, but the treatment causes lifelong side effects including dry mouth, difficulty swallowing, and loss of taste. Patients deemed unable to tolerate chemotherapy—for example, because of poor kidney function or older age—receive cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, and radiotherapy.
Study Methods and Findings
This study compared side effects and survival with the 2 treatments in 334 patients with HPV-positive throat cancer enrolled from 32 centers in the United Kingdom, Ireland, and the Netherlands. Patients were randomly allocated to radiotherapy and either cisplatin or cetuximab. Overall, 8 in 10 patients were male, and the average age was 57 years.
During the 2-year study, there were 10 recurrences and 6 deaths with cisplatin, compared to 29 recurrences and 20 deaths with cetuximab. Patients on cisplatin had a significantly higher 2-year overall survival rate (97.5%) than those on cetuximab (89.4%; P = .001, hazard ratio [HR] = 4.99, 95% confidence interval [CI] = 1.70–14.67). Cancer was over 3 times more likely to recur in 2 years with cetuximab compared to cisplatin, with recurrence rates of 16.1% vs 6.0%, respectively (P = .0007, HR = 3.39, 95% CI = 1.61–7.19).
There were no differences between groups in the overall number of side effects, or of acute or late severe (grade 3–5) toxic events, including dry mouth and difficulty swallowing. There were significantly more serious adverse events with cisplatin than with cetuximab.
Dr. Mehanna said, “Cetuximab did not cause less toxicity and resulted in worse overall survival and more cancer recurrence than cisplatin. This was a surprise—we thought it would lead to the same survival rates, but better toxicity. Patients with throat cancer who are HPV-positive should be given cisplatin, and not cetuximab, where possible.”
Commentary
Commenting on the study for ESMO, Branislav Bystricky, MUDr, Head, Medical and Radiation Oncology Department, University Hospital Trencín, Slovakia, said in a statement, “It was believed that cetuximab causes less side effects and was therefore a good option for patients with HPV-positive throat cancer who are young and expected to survive for several decades, as well as those less able to tolerate chemotherapy. This study shows that the best treatment choice for patients with HPV-positive throat cancer is cisplatin and radiotherapy. This combination gives ‘double’ the benefit, since it is more effective in terms of survival and does not worsen all-grade toxicity compared to cetuximab with radiotherapy.”
Dr. Bystricky noted that the results were in agreement with interim findings of the U.S. National Cancer Institute’s RTOG 1016 trial, which was reported at the 2018 ASTRO Annual Meeting. He said, “We now have two studies showing that these patients should not be given cetuximab. Future research should examine whether genotyping for the KRAS variant can select a group of patients who will benefit from cetuximab treatment with radiotherapy.”
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