In a phase II trial (RTOG 3501, TRYHARD) reported in JAMA Oncology, Wong et al found that the addition of lapatinib to chemoradiotherapy with cisplatin did not appear to improve progression-free survival in front-line therapy for stage III to IV non–human papillomavirus (HPV)-related head and neck carcinoma.
Study Details
One hundred and twenty-seven patients from sites in the United States and Canada were enrolled into the double-blind trial between October 2012 and April 2017. Patients were randomly assigned to receive chemoradiotherapy with radiotherapy at 70 Gy in 35 fractions over 6 weeks and cisplatin at 100 mg/m2 on days 1 and 22 of radiotherapy, plus either lapatinib (n = 63) or placebo (n = 64). Lapatinib at 1,500 mg/day or placebo were started 1 week before radiotherapy and continued through 3 months after radiotherapy completion. The primary endpoint of the study was progression-free survival.
Key Findings
Median follow-up was 4.1 years (range = 0.003–7.1 years). Median progression-free survival was 2.2 years (95% confidence interval [CI] = 1.3 years to not reached) in the lapatinib group vs 2.7 years (95% CI = 1.3–4.2 years) in the control group (hazard ratio [HR] = 0.91, 95% CI = 0.56-1.46, P = .34. Rates at 1 through 5 years were 70.4% vs 71.1%, 50.6% vs 56.2%, 43.1% vs 48.4%, 43.1% vs 37.1%, and 43.1% vs 34.6%.
No benefit in overall survival was observed in the lapatinib group vs the control group (HR = 1.06, 95% CI = 0.61–1.86, P = .58). Rates at 1 through 5 years were 86.2% vs 93.1%, 71.8% vs 76.0%, 62.6% vs 72.1%, 58.3% vs 58.0%, and 49.9% vs 55.1%, respectively.
Grade 3 or 4 acute adverse events occurred in 83.3% of patients in the lapatinib group vs 79.7% of the control group (P = .64); grade 3 or 4 late adverse events occurred in 44.4% vs 40.8% (P = .84).
The investigators concluded, “In this randomized clinical trial, dual EGFR-ERBB2 inhibition with lapatinib did not appear to enhance the benefit of chemoradiotherapy. Although the results of this trial indicate that accrual to a non-HPV head and neck carcinoma–specific trial is feasible, new strategies must be investigated to improve the outcome for this population with a poor prognosis.”
Stuart J. Wong, MD, of the Medical College of Wisconsin, Hematology and Oncology, Milwaukee, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by Novartis. For full disclosures of the study authors, visit jamanetwork.com.
