Reference Detail

Ref Type

Journal Article

PMID

(27311401)

Authors

Michel L, Ley J, Wildes TM, Schaffer A, Robinson A, Chun SE, Lee W, Lewis J, Trinkaus K, Adkins D

Title

Phase I trial of palbociclib, a selective cyclin dependent kinase 4/6 inhibitor, in combination with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Oral oncology	58		2016 Jul	41-8	Oral Oncol

URL

Abstract Text

To test the safety of the CDK4/6 inhibitor palbociclib with cetuximab in patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).A phase I trial using 3+3 design was performed to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of palbociclib with standard dose weekly cetuximab. Palbociclib was administered orally days 1-21 every 28days: dose level 1 (100mg/d) and 2 (125mg/d; approved monotherapy dose). Pharmacokinetic assessments were performed on cycle 2, day 15. Cyclin D1, p16(INK4a), and Rb protein expression were measured on pre-treatment tumor. Tumor response was assessed using RECIST1.1.Nine patients (five p16(INK4a) negative; four positive) were enrolled across dose levels 1 (n=3) and 2 (n=6) and none experienced a DLT. A MTD of palbociclib was not reached. Myelosuppression was the most common adverse event. Six of nine patients had cetuximab-resistant and 4/9 had platin-resistant disease. Disease control (DC) occurred in 89%, including partial response (PR) in two (22%) and stable disease in six (67%) patients. PRs occurred in p16(INK4a) negative HNSCC. Five patients (56%) had measurable decreases in tumor target lesions. In cetuximab-resistant HNSCC, best tumor response was PR in 1 and DC in 5 and median TTP was 112days (range: 28-168). In platin-resistant HNSCC, best tumor response: PR in 1, DC in 3 and median TTP was 112days (range: 28-112). The Cmax and AUC0-24h appeared comparable in patients receiving 125 vs 100mg dose of palbociclib.This trial, the first to evaluate a CDK4/6 inhibitor in HNSCC, determined that palbociclib 125mg/day on days 1-21 every 28days with cetuximab was safe. Tumor responses were observed, even in cetuximab- or platin-resistant disease.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
CDKN2A negative	head and neck squamous cell carcinoma	predicted - sensitive	Cetuximab + Palbociclib	Case Reports/Case Series	Actionable	In a Phase I trial, Erbitux (cetuximab) and Ibrance (palbociclib) combination therapy was safe and resulted in a disease control rate of 89% (8/9, 2 partial responses, 6 stable disease) in patients with recurrent or metastatic head and neck squamous cell carcinoma, both responders had CDKN2A-negative tumors (PMID: 27311401).	27311401