Induction chemotherapy followed by low-dose radiation/cetuximab appears safe, effective in HPV-associated OPSCC

CHICAGO — Induction chemotherapy followed by reduced-dose radiation with concurrent cetuximab induced high response rates and was well tolerated among patients with stage III/IV HPV-associated resectable oropharyngeal squamous cell carcinoma, according to results of a phase 2 study presented at the ASCO Annual Meeting.

“This study once again proves that HPV-positive oropharynx squamous cell cancer patients respond well to therapy and have an excellent prognosis,” Shanthi Marur, MD, of the department of oncology at The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, told HemOnc Today. “From retrospective studies, we now know among the HPV-positive patients there is a group considered low-risk for death and developing distant metastases. This study appears to indicate these low-risk patients would benefit from de-escalation of treatment. It will take many years for data to mature and the preliminary results should be interpreted cautiously.”

Previous research has shown that induction chemotherapy followed by standard radiation with 70 Gy paclitaxel resulted in improvements in 2-year PFS among patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).

Marur and colleagues set out to assess the effect of a reduced radiation dose of 54 Gy with concurrent cetuximab (Erbitux, Eli Lilly) in patients with HPV-positive stage III and Iva OPSCC who demonstrated clinical complete response to induction chemotherapy.

The treatment regimen consisted of induction chemotherapy for 3 weeks (paclitaxel 90 mg/m2 on days 1, 8 and 15, and cisplatin 75 mg/m2 on day 1), plus cetuximab 400 mg/m2 on day 1 of cycle 1 followed by 250 mg/m2 weekly from thereon for three complete cycles.

Patients then were assigned to either 54 Gy or 69.3 Gy of intensity-modulated radiation therapy (IMRT) plus once-weekly cetuximab.

Two-year PFS served as the primary outcome measure. Secondary outcome measures were 2-year OS, correlative biomarkers, quality of life, response rate and toxicity.

The analysis included 80 patients (mean age, 57 years; 93% white; 95% men). Six patients had biopsy of primary site after post-baseline measurements.

Overall, the rate of primary site clinical complete response to induction chemotherapy was 71.3% (95% CI, 60-80.8). The best overall clinical response to induction chemotherapy followed by low-dose radiation with concurrent cetuximab at primary site (complete response plus partial response) was 94%, with 5% unevaluable.

Common grade 3 and 4 toxicities reported during induction chemotherapy included neutropenia (11%) and rash (25%), while toxicities reported during radiation and concurrent cetuximab included mucositis (31%), dysphagia (17%) and radiation dermatitis (8%).

With a median follow-up of 16.2 months, researchers reported low failure rates and distant failure rates in the low-dose radiation therapy and cetuximab arm.

The 1-year PFS among patients with complete clinical response after induction chemotherapy followed by the low-dose IMRT plus cetuximab was 90% (95% CI, 0.77-0.96), and the 1-year PFS in the low-dose radiation therapy arm among ≤10 pack-year smokers was 97% (0.83-0.996).

The 1-year PFS looks promising in the low-dose IMRT arm, but longer follow up is necessary to determine if dose de-escalation is worthy of further study, Marur told HemOnc Today. “Induction chemotherapy appears to identify a group of patients who would benefit from dose de-escalation without compromising locoregional control,” Marur said. “Once again, the data is preliminary but promising.

“Currently, we do not recommend any changes in standard practice,” Marur added. “The induction chemotherapy regimen in this study looks promising, with high response rates and a low toxicity profile. This needs to be tested in a larger phase 3 trial and compared to [docetaxel/cisplatin/5-fluorouracil], the current standard regimen.”

For more information:

Marur S. Abstract #6005. Presented at: ASCO Annual Meeting; May 31-June 4, 2013; Chicago.

Disclosure: The researchers report research funding and honoraria from, as well as consultant or advisory roles with Bristol-Myers Squibb.