Cetuximab versus cisplatin in patients with human papillomavirus (HPV)-positive oropharyngeal cancer

In the randomized RTOG-1016 trial (NCT01302834), patients with HPV-positive (determined by central confirmation of p16 immunohistochemistry) oropharyngeal cancer were randomly assigned (1:1) to receive either radiation therapy with cetuximab or radiation therapy with cisplatin. This trial aimed to determine whether treatment with radiation therapy and cetuximab produced noninferior survival compared with treatment using radiation therapy and cisplatin. Of the 987 patients enrolled, 849 were randomly assigned to receive radiation therapy plus cetuximab (n = 425) or radiation therapy plus cisplatin (n = 424). Subsequently, 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were determined to be eligible. Patients received 70 Gy of radiation therapy in 6 weeks accelerated (six fractions/week) with either two cycles of cisplatin (100 mg/m2) every 3 weeks or weekly cetuximab.[37][Level of evidence A1]

In the randomized RTOG-1016 trial (NCT01302834), patients with HPV-positive (determined by central confirmation of p16 immunohistochemistry) oropharyngeal cancer were randomly assigned (1:1) to receive either radiation therapy with cetuximab or radiation therapy with cisplatin. This trial aimed to determine whether treatment with radiation therapy and cetuximab produced noninferior survival compared with treatment using radiation therapy and cisplatin. Of the 987 patients enrolled, 849 were randomly assigned to receive radiation therapy plus cetuximab (n = 425) or radiation therapy plus cisplatin (n = 424). Subsequently, 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were determined to be eligible. Patients received 70 Gy of radiation therapy in 6 weeks accelerated (six fractions/week) with either two cycles of cisplatin (100 mg/m2) every 3 weeks or weekly cetuximab.[37][Level of evidence A1]

After a median follow-up duration of 4.5 years, radiation therapy plus cetuximab did not meet the noninferiority criteria for OS (HR, 1.45; one-sided 95% upper CI, 1.94; P = .5056 for noninferiority; one-sided log-rank P = .0163).[38][Level of evidence A1]

In the randomized RTOG-1016 trial (NCT01302834), patients with HPV-positive (determined by central confirmation of p16 immunohistochemistry) oropharyngeal cancer were randomly assigned (1:1) to receive either radiation therapy with cetuximab or radiation therapy with cisplatin. This trial aimed to determine whether treatment with radiation therapy and cetuximab produced noninferior survival compared with treatment using radiation therapy and cisplatin. Of the 987 patients enrolled, 849 were randomly assigned to receive radiation therapy plus cetuximab (n = 425) or radiation therapy plus cisplatin (n = 424). Subsequently, 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were determined to be eligible. Patients received 70 Gy of radiation therapy in 6 weeks accelerated (six fractions/week) with either two cycles of cisplatin (100 mg/m2) every 3 weeks or weekly cetuximab.[37][Level of evidence A1]

The estimated 5-year OS rate was 77.9% (95% CI, 73.4%–82.5%) in the cetuximab group versus 84.6% (80.6%–88.6%) in the cisplatin group.

In the randomized RTOG-1016 trial (NCT01302834), patients with HPV-positive (determined by central confirmation of p16 immunohistochemistry) oropharyngeal cancer were randomly assigned (1:1) to receive either radiation therapy with cetuximab or radiation therapy with cisplatin. This trial aimed to determine whether treatment with radiation therapy and cetuximab produced noninferior survival compared with treatment using radiation therapy and cisplatin. Of the 987 patients enrolled, 849 were randomly assigned to receive radiation therapy plus cetuximab (n = 425) or radiation therapy plus cisplatin (n = 424). Subsequently, 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were determined to be eligible. Patients received 70 Gy of radiation therapy in 6 weeks accelerated (six fractions/week) with either two cycles of cisplatin (100 mg/m2) every 3 weeks or weekly cetuximab.[37][Level of evidence A1]

PFS was significantly lower in the cetuximab group than in the cisplatin group (HR, 1.72; 95% CI, 1.29–2.29; P = .0002; 5-year PFS rate 67.3%; 95% CI, 62.4%–72.2% vs. 78.4%, 73.8%–83.0%), and locoregional failure was significantly higher in the cetuximab group than in the cisplatin group.

In the randomized RTOG-1016 trial (NCT01302834), patients with HPV-positive (determined by central confirmation of p16 immunohistochemistry) oropharyngeal cancer were randomly assigned (1:1) to receive either radiation therapy with cetuximab or radiation therapy with cisplatin. This trial aimed to determine whether treatment with radiation therapy and cetuximab produced noninferior survival compared with treatment using radiation therapy and cisplatin. Of the 987 patients enrolled, 849 were randomly assigned to receive radiation therapy plus cetuximab (n = 425) or radiation therapy plus cisplatin (n = 424). Subsequently, 399 patients assigned to receive cetuximab and 406 patients assigned to receive cisplatin were determined to be eligible. Patients received 70 Gy of radiation therapy in 6 weeks accelerated (six fractions/week) with either two cycles of cisplatin (100 mg/m2) every 3 weeks or weekly cetuximab.[37][Level of evidence A1]

Acute moderate to severe toxicity (77.4%, 95% CI, 73.0%–81.5% vs. 81.7%, 77.5%–85.3%; P = .1586) and late moderate to severe toxicity (16.5%, 95% CI, 12.9%–20.7% vs. 20.4%, 16.4%–24.8%; P = .1904) were similar between the cetuximab and cisplatin groups.

De-ESCALaTE HPV [NCT01874171] was an open-label, randomized, controlled, phase III trial at 32 head and neck treatment centers in Ireland, the Netherlands, and the United Kingdom. It included patients aged 18 years or older with HPV-positive, low-risk oropharyngeal cancer (nonsmokers or lifetime smokers with a smoking history of <10 pack-years).[39] Patients were randomly assigned (1:1) to receive, in addition to radiation therapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grades 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group).

De-ESCALaTE HPV [NCT01874171] was an open-label, randomized, controlled, phase III trial at 32 head and neck treatment centers in Ireland, the Netherlands, and the United Kingdom. It included patients aged 18 years or older with HPV-positive, low-risk oropharyngeal cancer (nonsmokers or lifetime smokers with a smoking history of <10 pack-years).[39] Patients were randomly assigned (1:1) to receive, in addition to radiation therapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grades 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group).

Overall (acute and late) severe (grades 3–5) toxicity did not differ significantly between treatment groups at 24 months (mean number of events per patient, 4.8 [95% CI, 4.2–5.4] with cisplatin vs. 4.8 [4.2–5.4] with cetuximab; P = .98).[39][Level of evidence A1]

De-ESCALaTE HPV [NCT01874171] was an open-label, randomized, controlled, phase III trial at 32 head and neck treatment centers in Ireland, the Netherlands, and the United Kingdom. It included patients aged 18 years or older with HPV-positive, low-risk oropharyngeal cancer (nonsmokers or lifetime smokers with a smoking history of <10 pack-years).[39] Patients were randomly assigned (1:1) to receive, in addition to radiation therapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grades 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group).

At 24 months, overall all-grade toxicity did not differ significantly (mean number of events per patient, 29.2 [95% CI, 27.3–31.0] with cisplatin vs. 30.1 [28.3–31.9] with cetuximab; P = .49).

De-ESCALaTE HPV [NCT01874171] was an open-label, randomized, controlled, phase III trial at 32 head and neck treatment centers in Ireland, the Netherlands, and the United Kingdom. It included patients aged 18 years or older with HPV-positive, low-risk oropharyngeal cancer (nonsmokers or lifetime smokers with a smoking history of <10 pack-years).[39] Patients were randomly assigned (1:1) to receive, in addition to radiation therapy (70 Gy in 35 fractions), either intravenous cisplatin (100 mg/m2 on days 1, 22, and 43 of radiation therapy) or intravenous cetuximab (400 mg/m2 loading dose followed by seven weekly infusions of 250 mg/m2). The primary outcome was overall severe (grades 3–5) toxicity events at 24 months from the end of treatment. The primary outcome was assessed by intention-to-treat and per-protocol analyses. Between Nov 12, 2012, and Oct 1, 2016, 334 patients were recruited (166 in the cisplatin group and 168 in the cetuximab group).

OS was inferior and local recurrence rate was higher in the cetuximab arm. The 2-year OS rate was 97.5% for the cisplatin group versus 89.4% for the cetuximab group (HR, 5.0; 95% CI, 1.7–14.7; P = .001), and the 2-year recurrence rate was 6.0% for the cisplatin group versus 16.1% for the cetuximab group (HR, 3.4; 1.6–7.2; P = .0007).