Palbociclib Plus Cetuximab in Platinum- and Cetuximab-Resistant HPV-Unrelated Head and Neck Cancer


Key Points

  • Activity of the combination was observed in platinum-resistant and cetuximab-resistant disease.
  • Objective response rates were 39% in patients who had experienced disease progression on platinum therapy but were cetuximab-naïve, and 19% in patients with cetuximab-resistant disease.

In a phase II study reported in The Lancet Oncology, Adkins et al 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.

Study Protocol and Responses

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.

Adverse Events

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.”

Douglas Adkins, MD, of the Division of Medical Oncology, Washington University School of Medicine, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Pfizer. For full disclosures of the study authors, visit

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