Cyclin Dependent Kinase (CDK)4/6 Inhibitor, PD0332991 in Advanced Non-small Cell Lung Cancer NSCLC.

The oral drug PD0332991 is a highly selective reversible inhibitor of cyclin-dependent kinases 4 & 6 that is being studied for use in the treatment of advanced non-small cell lung cancer.

Inclusion criteria

• Histologically or cytologically proven non small cell lung cancer
• Stage IV (M1a or M1b) disease. Patients may also have recurrence of early-stage disease or locally advanced disease with the presence of new distant metastases.
• Cyclin dependent kinase (CDK)N2a (p16) protein absent or expressed at a low level in tumor biopsy specimen
• Failed or intolerant of at least one prior systemic chemotherapy regimen (there is no maximum number of prior chemotherapy regimens)
• Eastern cooperative oncology group (ECOG) performance status 0-2
• Age >18 years.
• Adequate organ and bone marrow function
• Measurable disease by standard RECIST v1.1 criteria
• Life expectancy of greater than 3 months

Exclusion criteria

• Inability to understand or sign the informed consent document
• Inability or unwillingness to take oral medications
• No available tissue specimen for p16 analysis
• Chemotherapy or radiotherapy within 3 weeks prior to beginning the study drug
• Other investigational agents within 4 weeks prior to beginning the study drug
• All side effects from previous chemotherapy, radiotherapy or investigational agents not resolved, returned to baseline or returned to Grade 1 toxicity (exceptions are grade 2 alopecia and grade 2 peripheral neuropathy)
• Major surgery within 4 weeks prior to beginning the study drug
• Surgical scar from previous surgery not healed prior to beginning the study drug
• High-dose or chronic steroid use
• High-dose statins within 7 days
• History of rhabdomyolysis
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled diabetes, stroke or myocardial infarction within 3 months, or psychiatric illness/social situations that would limit compliance with study requirements.
• Baseline corrected QT interval (QTc) >470ms
• Pre-existing clinically significant cardiac, hepatic or renal dysfunction at the discretion of the treating physician
• Untreated or uncontrolled (symptomatic or asymptomatic) brain metastases
• Leptomeningeal carcinomatosis
• Inability or unwillingness to use contraception during the treatment period by patients with reproductive potential.
• Pregnant or breastfeeding women
• HIV-positive patients on combination antiretroviral therapy