Top Line: Does dual EGFR and ERBB2 inhibition improve outcomes for head and neck cancer treated with chemoradiation?
The Study: In RTOG 0522, adding the EGFR inhibitor cetuximab to cisplatin and radiation did not improve treatment outcomes for patients with locally advanced head and neck squamous cell carcinoma. Lapatinib is a small molecule tyrosine kinase inhibitor that blocks both EGFR and ERBB2 (HER2). TRYHARD was a randomized phase 2 trial that hypothesized lapatinib would be a more effective addition to chemoradiation than cetuximab for locally advanced, non-HPV-mediated HNSCC. 127 patients were randomized to receive standard RT (70 Gy in 35 fractions over 6 weeks with 6 fractions given per week) and 2 cycles of Q3wk cisplatin with or without daily lapatinib. Unfortunately, the addition of lapatinib did not significantly improve median PFS (2.2 v 2.7 years) or the rate of PFS at 2 years (56.2% v 50.2%). Likewise, there was no improvement in OS or locoregional failure. On the bright side, adding lapatinib to CRT did not significantly increase acute or late toxicity.
TBL: In TRYHARD, the addition of lapatinib to concurrent cisplatin and radiation did not improve any treatment outcomes for HPV-negative HNSCC. | Wong, JAMA Oncol 2023
The Study: In RTOG 0522, adding the EGFR inhibitor cetuximab to cisplatin and radiation did not improve treatment outcomes for patients with locally advanced head and neck squamous cell carcinoma. Lapatinib is a small molecule tyrosine kinase inhibitor that blocks both EGFR and ERBB2 (HER2). TRYHARD was a randomized phase 2 trial that hypothesized lapatinib would be a more effective addition to chemoradiation than cetuximab for locally advanced, non-HPV-mediated HNSCC. 127 patients were randomized to receive standard RT (70 Gy in 35 fractions over 6 weeks with 6 fractions given per week) and 2 cycles of Q3wk cisplatin with or without daily lapatinib. Unfortunately, the addition of lapatinib did not significantly improve median PFS (2.2 v 2.7 years) or the rate of PFS at 2 years (56.2% v 50.2%). Likewise, there was no improvement in OS or locoregional failure. On the bright side, adding lapatinib to CRT did not significantly increase acute or late toxicity.
TBL: In TRYHARD, the addition of lapatinib to concurrent cisplatin and radiation did not improve any treatment outcomes for HPV-negative HNSCC. | Wong, JAMA Oncol 2023