No Benefit Adding Lapatinib to Chemoradiotherapy for Patients With Non-HPV Head and Neck Carcinoma

According to a phase 2 clinical trial, the addition of lapatinib did not improve the benefit of chemoradiotherapy for patients with non-human papillomavirus (HPV) head and neck carcinoma.

While chemoradiotherapy with cisplatin plus an anti-EGFR antibody has improved overall survival in this patient population, there is preclinical data to “suggest that a small-molecule tyrosine kinase inhibitor dual EGFR and [HER2] inhibitor may be more effective than anti-EGFR antibody therapy in [head and neck carcinoma,” as Stuart J. Wong, MD, Medical College of Wisconsin, Milwaukee, and coauthors wrote.

In this multicenter, double-blind phase 2 trial, 142 patients with stage III to stage IV carcinoma of the oropharynx, larynx, and hypopharynx were enrolled between October 18, 2012, and April 18, 2017. Of the 142 patients enrolled, 127 were randomized on a 1-to-1 basis to receive 70 Gray over 6 weeks plus 2 cycles of cisplatin every 3 weeks, plus either 1500mg lapatinib daily (n = 63, lapatinib group) or placebo (n = 64, placebo group). The primary end point of this study was progression-free survival (PFS) with overall survival (OS) as the secondary end point.

In the final analysis, there was no improvement seen in either the PFS (hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.56 to 1.46; P = .34) or the OS (HR, 1.06; 95% CI, 0.61 to 1.86; P = .58) in the lapatinib group. There were no significant differences in grade 3/4 adverse events (83.3% in the lapatinib group vs 79.7% in the placebo group; P = .64) or late adverse event rates (44.4% vs 40.8%; P = .84) between the lapatinib and placebo groups.

Dr Wong et al concluded, “Despite preclinical activity of dual [EGFR] and [HER2] inhibition in head and neck squamous cell carcinoma, lapatinib is insufficiently effect to warrant further study in the definitive setting with chemoradiotherapy.” They added, “new strategies must be investigated to improve the outcome for this population with a poor prognosis.”

Source:

Wong SJ, Torres-Saavedra PA, Saba NF, et al. Radiotherapy plus cisplatin with or without lapatinib for non-human papillomavirus head and neck carcinoma: A phase 2 randomized clinical trial. JAMA Oncol. Published online: September 28, 2023. doi:10.1001/jamaoncol.2023.3809