Cetuximab and radiotherapy no better than chemoradiotherapy in SCC of head and neck

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.

CHICAGO – Cetuximab combined with radiotherapy was no better than conventional chemoradiotherapy for the treatment of locally advanced squamous cell carcinomas of the head and neck, based on data from a phase II/III study presented at the annual meeting of the American Society of Clinical Oncology.

"No differences in activity and efficacy were observed between the two treatments," said Dr. Maria Grazia Ghi, of Ospedale Civile Venezia in Venice, Italy. However, while the treatments did not significantly differ in severe toxicities, compliance was better with concomitant therapy than with chemoradiotherapy (CRT), with more patients completing treatment and fewer having unplanned treatment interruptions, she noted.

The phase II/III study compared concomitant CRT with cetuximab and radiotherapy (CET/RT) – with and without induction therapy – with docetaxel, cisplatin, and 5-fluorouracil (TPF) in treatment-naive patients with unresectable squamous cell carcinomas of the head and neck. In 2010, phase II results were reported indicating that TPF induction was feasible in this population and did not compromise subsequent CRT. In addition, TPF induction chemotherapy significantly increased the chance of complete response (P = .004). Preliminary in-field toxicity results were reported at the 2012 ASCO meeting.

At this year’s meeting, data were presented on overall survival with or without induction therapy, and on grade 3 or worse in-field toxicities with CRT vs. CET/RT.

A total of 420 patients with squamous cell cancers of the oral cavity, hypopharynx, or oropharynx with good performance status (Eastern Cooperative Oncology Group 0 or 1) were randomized in a 2 x 2 factorial design to receive either TPF induction every 3 weeks for three cycles, or no induction, with each group then further randomized to either two cycles of cisplatin and 5-fluorouracil (5-FU) delivered concomitantly with 70 Gy of radiation divided into 35 fractions, or 7 weeks of cetuximab and the same radiotherapy dose.

There were no significant differences in the primary endpoint, in-field toxicities, with grade 3 mucositis occurring in 35% of patients on CRT, compared with 34% on CET/RT. Grade 4 mucositis occurred in 3% and 2% of patients, respectively. Grade 3 or 4 skin toxicities were also similar between the groups, with grade 3 adverse events seen in 12% of patients on CRT, vs. 19% on CET/RT, and grade 4 events occurring in 1% and 0.6%, respectively.

However, treatment compliance was significantly better with CRT, with 91% of patients assigned to this therapy completing both cycles, compared with 81% of patients assigned to CET/RT (P = .005). In addition, 23% of patients on CRT required interruption of radiotherapy for more than 3 consecutive days, compared with 38% of patients on CET/RT (P less than .001).

Median progression-free survival rates were 20.9 months for CRT vs. 20.7 months for CET/RT, a difference that was not significant. At 2 years, 48% of patients on CRT and 43% on CET/RT were alive without progression.

Median overall survival durations were 39.5 vs. 38.2 months, and overall survival at 2 years’ follow-up was 65% and 59%, respectively; the differences were not statistically significant.

There was an evident trend toward better progression-free survival and overall survival on CRT for patients with oropharyngeal cancers, but these differences were not significant at most recent follow-up, Dr. Ghi said.

Response rates to therapy, regardless of induction status, did not differ significantly, with 34% on CRT and 38% on CET/RT having a complete response, 47% and 46% having partial responses, 5% and 6% having stable disease, and 14% and 11% experiencing disease progression.

Invited discussant Dr. Danny Rischin, professor of oncology at the Peter MacCallum Cancer Centre in Melbourne, noted that the study was limited by its inclusion of patients from the randomized phase II induction comparison who were not later randomized to cetuximab, thereby confounding results of the phase III portion of the study. He added that it is still unknown whether there is an interaction between induction chemotherapy and the type of subsequent concomitant treatment, since the phase II data on the induction phase have not yet been reported.

Additionally, it is uncertain whether cisplatin/5-FU with a lower dose of cisplatin as given in this study – 20 mg/m² on days 1-4 – is equivalent to three cycles of cisplatin when given with conventionally fractionated radiation, Dr. Rischin said.

"We really need to wait for the final study results, including outcomes with TPF, and HPV [human papillomavirus] analyses, particularly for understanding what was happening in oropharyngeal cancer patients, and we need to see interaction results before drawing any final conclusions," he added.

Dr. Ghi reported having no relevant disclosures. Dr. Rischin reported receiving research funding from Genentech and Serono.