In a phase II study reported in The Lancet Oncology, Douglas Adkins, MD, and colleagues found that the combination of the cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib and the EGFR inhibitor cetuximab showed activity in patients with either platinum- or cetuximab-resistant human papillomavirus (HPV)-unrelated head and neck squamous cell carcinoma.
Douglas Adkins, MD
In the study, 62 patients from eight sites who had experienced disease progression on platinum therapy but were cetuximab-naive (group 1; n = 30, 28 in the per-protocol population) and those with cetuximab-resistant disease (group 2; n = 32, 27 in the per-protocol population) were treated between October 2015 and November 2018. They received palbociclib at 125 mg/d on days 1 to 21, and cetuximab at 400 mg/m² on day 1 of cycle 1 and then 250 mg/m² once per week in 28-day cycles. The primary endpoint was objective response in the per-protocol population.
Median follow-up was 5.4 months for group 1 and 5.5 months for group 2. Objective response was observed in 11 (39%) of 28 evaluable patients in group 1 and in 5 (19%) of 27 evaluable patients in group 2. Median durations of response were 4.0 and 6.0 months, and median progression-free survival was 5.4 and 3.5 months, respectively.
Treatment-related grade 3 or 4 adverse events occurred in 52% of patients (60% of group 1 and 44% of group 2), with palbociclib-related events occurring in 42%; the most common palbociclib-related grade 3 or 4 adverse event was neutropenia (34%). Treatment-related serious adverse events occurred in three patients in group 1 (febrile neutropenia, fatigue, and infusion-related reaction). No treatment-related deaths were reported.
The investigators concluded, “In patients with platinum-resistant or cetuximab-resistant HPV-unrelated head and neck squamous cell carcinoma, [the combination of] palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated head and neck squamous cell carcinoma.” ■