Lead Investigator: Khandan Keyomarsi, The University of Texas MD Anderson Cancer Center
Title of Proposal Research: Validation of Predictive Molecular Biomarker for Predicting Response to Cyclin-Dependent Kinase 4 and 6 (CDK4/6) Inhibitors in Breast Cancer Using Data from PALOMA-2 and PALOMA-3 Studies
Vivli Data Request: 10471
Funding Source: CPRIT multi-investigator grant RP180712
Potential Conflicts of Interest: None
Summary of the Proposed Research:
Breast cancer is a major health issue affecting millions of people worldwide. One type of breast cancer, called hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-), can be particularly difficult to treat, especially when it spreads to other parts of the body, which is known as metastatic breast cancer (mBC).
In HR+ breast cancer, the cancer cells have certain proteins, called hormone receptors, that can attach to hormones like estrogen and progesterone. These hormones can help the cancer cells grow. If the cancer cells have these receptors, it means the cancer is “hormone receptor-positive” (HR+), which occurs in about two-thirds of breast cancers. This type of cancer can often be treated with medicines that block the hormones, slowing the cancer’s growth.
HER2 is a protein located on the surface of breast cells that helps regulate cell growth – too much HER2 can cause cells to grow uncontrollably. HER2-negative (HER2-) means the cancer cells do not have an excess of the HER2 protein, which means that specific HER2-targeted treatments will not work for them. Understanding whether a breast cancer is HR+ and HER2- is important because it helps doctors choose the best treatment.
HR+ and HER2- breast cancer can be especially challenging to treat when it spreads, and current treatments may not work for everyone. In this form of breast cancer, treatments that target hormone receptors are often used. A newer class of drugs called cyclin-dependent kinase 4/6 inhibitors (CDK4/6 inhibitors) has shown promise in treating this type of cancer by slowing down the growth of cancer cells. However, not all patients respond equally well to these drugs, which highlights the need for better ways to predict which patients will benefit most from them.
Our research aims to address this critical need by identifying and validating biomarkers—molecules in the blood or tissues that can indicate how well a treatment will work. Specifically, we are focusing on biomarkers that can predict how well patients with HR+/HER2- metastatic breast cancer will respond to CDK4/6 inhibitors, like palbociclib. If successful, this could lead to more personalized treatment plans, improving outcomes and reducing unnecessary side effects for patients.
To achieve this, we will use a method called single-cell RNA sequencing. This technique allows us to examine the gene activity of individual cancer cells, helping us identify specific biomarkers associated with responses to CDK4/6 inhibitors. To confirm these findings, we will use data from two large clinical trials known as PALOMA-2 and PALOMA-3. These trials involved patients with HR+/HER2- breast cancer who were treated with palbociclib as either their first or second treatment option. By analyzing the data from these trials, we aim to validate whether our identified biomarkers can accurately predict patient responses to treatment.
Requested Studies:
MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 TRIAL OF FULVESTRANT (FASLODEX (REGISTERED)). WITH OR WITHOUT PD-0332991 (PALBOCICLIB) +/- GOSERELIN IN WOMEN WITH HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE THERAPY
Data Contributor: Pfizer Inc.
Study ID: NCT01942135
Sponsor ID: A5481023
A RANDOMIZED, MULTICENTER, DOUBLE-BLIND PHASE 3 STUDY OF PD-0332991 (ORAL CDK 4/6 INHIBITOR) PLUS LETROZOLE VERSUS PLACEBO PLUS LETROZOLE FOR THE TREATMENT OF POSTMENOPAUSAL WOMEN WITH ER (+), HER2 (-) BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE
Data Contributor: Pfizer Inc.
Study ID: NCT01740427
Sponsor ID: A5481008