Palbociclib and Letrozole or Fulvestrant in Treating Patients With Estrogen Receptor Positive, HER2 Negative Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. To estimate the safety and tolerability (adverse event rate) of the combination of
palbociclib and letrozole or fulvestrant in adults age 70 or older with estrogen
receptor-positive, HER2-negative metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To describe the full toxicity profile including all grade 2 and higher adverse events (per
National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE]
version [v.] 5.0), specifically estimating the rate of grade 2 and higher myelosuppression
(neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal
(GI) side effects (nausea, diarrhea, decreased appetite, vomiting, mucositis-oral), fatigue,
neuropathy, and thromboembolism.

II. To describe rates of dose reductions, dose holds, and hospitalizations. III. To estimate
median time to treatment failure, including progression free survival and overall survival.

IV. To estimate the rate of adherence to palbociclib, letrozole and fulvestrant.

V. To explore factors other than chronologic age that can affect toxicity rates as identified
using a cancer-specific geriatric assessment.

VI. To describe the results of the Overall Treatment Utility (OTU). VII. To determine the
degree of agreement between patient-reported adverse events (AEs) using Patient Reported
Outcomes (PRO)-CTCAE measures and those reported using traditional collections for AEs.

VIII. To examine the association between sarcopenia and the development of toxicity and
adverse events.

OUTLINE:

Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Patients also receive
letrozole PO QD on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1
and on day 1 of subsequent courses per Doctor of Medicine (MD) discretion. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Inclusion Criteria:

- Documentation of disease: estrogen receptor positive, HER2 negative metastatic breast
cancer; histologic confirmation is required

- Measurable disease or non-measurable disease

- Planning to begin endocrine therapy for metastatic disease; one prior line of
endocrine therapy or chemotherapy for metastatic disease is allowed

- No prior therapy with a CDK inhibitor

- Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE
grade =< 1 (except alopecia) prior to registration

- No untreated brain metastases; patients with treated brain metastases must have
completed treatment with steroids to be eligible

- No second malignancies other than non-melanoma skin cancers or cervical carcinoma in
situ

- No active infection requiring treatment with antibiotics

- Patients must be able to swallow and retain oral medication

- Patients must be able to read and comprehend English or Spanish

- Absolute neutrophil count (ANC) >= 1500/mm^3 (1.5 x 10^9/L)

- Platelet count >= 100,000/mm^3 (100 x 10^9/L)

- Creatinine clearance >= 30 ml/min calculated using the Cockcroft-Gault formula

- Total serum bilirubin =< 1.5 upper limit of normal (ULN) (< 3 ULN if Gilbert's
disease)

- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x ULN (=<
5.0 x ULN if liver metastases present)

- Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN if bone or liver metastases present)