Abstract 4758
Background
HPV induces many alterations in CDK4-Cyclin D-Rb and apoptotic pathways such as up-regulation of p16, loss of Rb and p53 functions in SCCHN carcinogenesis. Loss of p16 expression is known as a poor prognostic marker in SCCHN for survival. Palbociclib is a highly selective inhibitor of CDK4/6 by blocking Rb phosphorylation with radiosensitizing activity in preclinical studies. Addition of palbociclib to cetuximab and IMRT provides a strong rationale to improve efficacy of treatment in locally advanced SCCHN, especially in p16/HPV-negative tumour.
Methods
This is a phase I study designed to determine the maximum tolerated dose (MTD) and toxicity of palbociclib, cetuximab, and IMRT, using a classical 3 + 3 design (NCT03024489). The study included locally advanced SCCHN of oral cavity, oropharynx, larynx, and hypopharynx. Palbociclib dose was escalated with 3 dose levels (DLs), starting from 75 to 125 mg/d orally for 21 day-on and 7 day-off for 2 cycles. For all DLs, cetuximab was administered at 400 mg/m2IV on day -7 and then 250 mg/m2weekly for 7 weeks. IMRT was delivered 5 day-on and 2 day-off with a total dose of 70 Gy for 33 fractions. MRI and PET scans pre- and post-treatment was used to evaluate preliminary efficacy.
Results
A total of 13 eligible patients were enrolled in the dose escalation cohort. No MTD was observed. One DLT, febrile neutropenia (FN) was reported in 1 of 7 patients who received 125 mg of palbociclib (DL3) at the 6thweek of IMRT. The FN recovered without G-CSF support within 7 days after discontinuation of palbociclib. Overall, toxicities were related to cetuximab and IMRT. Complete response was observed in 7 of 10 evaluable patients (70%), while overall objective response was demonstarted in 9 of 10 patients (90%).
Conclusions
The recommended phase 2 dose was palbociclib 125 mg/d for 21 days on and 7 days off with full standard dose of cetuximab and IMRT for locally advanced SCCHN. MTD was not achieved. The combination was well tolerated with promising preliminary efficacy. The expansion cohort of palbociclib 125 mg/d is currently accruing up to 15 locally advanced p16-negative SCCHN patients.
Clinical trial identification
NCT#03024489.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Pfizer.
Disclosure
N. Ngamphaiboon: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy: Boehringer Ingelheim; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Taiho. T. Siripoon: Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Boehringer Ingelheim. S. Lukerak: Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca. N. Sankaseam: Research grant / Funding (institution): Roche; Research grant / Funding (institution): MSD; Research grant / Funding (institution): AstraZeneca. E. Sirachainan: Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self): Sanofi/Aventis; Honoraria (self): Merck; Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Mundipharma; Honoraria (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): LF Asia; Honoraria (self): Diethelm Keller Logistics; Honoraria (self): BMS; Honoraria (self): Boehringer Ingelheim. All other authors have declared no conflicts of interest.
Resources from the same session
2494 - CAR-T Nursing Education at a UK Specialist Cancer Hospital
Presenter: Rose Ellard
Session: Poster Display session 3
Resources:
Abstract
2438 - Professional Quality of Life, Perceived Stress and Psychological Resistance Levels of Oncology-Hematology Nurses and the Factors Affecting
Presenter: Tugba Pehlivan
Session: Poster Display session 3
Resources:
Abstract
3541 - Representation of cancer survivors’ preferences in policies for supportive care: Implications for oncology nursing
Presenter: Samantha Mayo
Session: Poster Display session 3
Resources:
Abstract
5093 - Vaginal moisturizing post PDR-Pulse Dose Rate Brachytherapy.
Presenter: Pilar Fernández
Session: Poster Display session 3
Resources:
Abstract
1066 - The stomized, chemo and radiotreated patient vs untreated patient: complications and comparison with data literature
Presenter: Cristoforo Ferrero
Session: Poster Display session 3
Resources:
Abstract
1724 - Evaluating the role of clinical nurse specialist
Presenter: Anita Zeneli
Session: Poster Display session 3
Resources:
Abstract
3753 - Role of the Advanced Practice Nurse (APN) in a Functional Unit for Lung cancer at the Catalan Institute of Oncology
Presenter: Isabel Brao
Session: Poster Display session 3
Resources:
Abstract
2676 - A bottom-up approach for prioritising the scientific activities of the Italian Association of Cancer Nurses (AIIAO): rationale and topic identification
Presenter: Valentina Biagioli
Session: Poster Display session 3
Resources:
Abstract
575 - Investigating quality of care for people with cancer and dementia
Presenter: Naomi Farrington
Session: Poster Display session 3
Resources:
Abstract
5578 - Two years of BRCA1 and BRCA2 somatic External Quality Assessment with Gen&tiss Tiss scheme in France
Presenter: Kelly Dufraing
Session: Poster Display session 3
Resources:
Abstract