The impact of palbociclib (Ibrance) on overall survival for metastatic breast cancer patients in the PALOMA-3 trial

Expert Guidelines

The National Comprehensive Cancer Network (NCCN) brings together national expert panels that create guidelines for cancer treatment. NCCN guidelines for the treatment of advanced or metastatic ER-positive breast cancer include the following:

Genetic testing

• All people diagnosed with metastatic breast cancer meet guidelines for genetic counseling and testing. 

NCCN preferred treatment options

The NCCN lists the following as preferred treatments for metastatic ER-positive and HER2-negative breast cancer:

• Targeted therapy for people with BRCA1 or BRCA2 mutations:
  • The NCCN lists Lynparza (olaparib) or Talzenna (talazoparib) for people with an inherited BRCA1 or BRCA2 mutation. 
• First line therapy
  • The NCCN lists as the preferred treatment combination of hormonal therapy (aromatase inhibitor or Fulvestrant) + targeted therapy with a CDK4/6 inhibitor:
    •  abemaciclib (Verzenio), palbocicib (Ibrance) or ribociclib (Kisqali). 
• For second, third or later lines of therapy, the NCCN lists the following targeted therapies or combinations treatments:
  • a combination of hormonal therapy (aromatase inhibitor or Fulvestrant) plus targeted therapy with a CDK4/6 inhibitor for people who have not previously received a CDK4/6 inhibitor
  • Enhertu (trastuzumab deruxtecan) for people whose tumors are HER2-low (HER2 1+ or HER2 2+), who received chemotherapy in the metastatic setting and their cancer no longer responds to hormonal therapy 
  • Piqray (apelisib) for cancers that test positive for a PIK3CA-mutation
  • Oserdu (elacestrant) for HR-positive, HER2-negative cancers that test positive for an ESR1 mutation
  • Lynparza (olaparib) or Talzenna (talazoparib) for BRCA1/BRCA2 for tumors with BRCA1 or BRCA2 mutation
  • a combination of everolimus and hormonal therapy
  • hormonal therapy alone
  • Trodelvy (sacituzumab govitecan-hziy) for HR-positive, HER2-negative cancers after prior treatment including hormone therapy, a CDK4/6 inhibitor and at least two lines of chemotherapy (including a taxane)

Questions To Ask Your Health Care Provider

• What treatment therapy or therapies are best for my circumstance?
• Are there combination therapies that I should consider?
• Should I consider treatment with a CDK4/6 inhibitor for my metastatic breast cancer?
• What are the pros and cons of various treatments for my metastatic breast cancer?
• Are there clinical trials enrolling participants with metastatic breast cancer that are appropriate for me?

Open Clinical Trials

The following studies look at treatment for people with metastatic ER-positive breast cancer.  

• NCT05501886: Gedatolisib Plus Fulvestrant With or Without Palbociclib vs Standard-of-Care for the Treatment of Patients With Advanced or Metastatic HR+/HER2- Breast Cancer (VIKTORIA-1).  This study is looking at the efficacy and safety of the selective estrogen receptor degrader (SERD) gedatolisib plus fulvestrant with or without palbociclib for the treatment of patients with locally advanced or metastatic HR+/HER2- breast cancer following progression on or after CDK4/6 and aromatase inhibitor therapy.
• NCT04975308: A Study of Imlunestrant, Investigator's Choice of Endocrine Therapy, and Imlunestrant Plus Abemaciclib in Participants With ER+, HER2- Advanced Breast Cancer. This study will evaluate the efficacy and safety of the selective estrogen receptor degrader (SERD) imlunestrant, how it works compared to standard hormone therapy, and how well imlunestrant with abemaciclib works compared to imlunestrant in participants with breast cancer that is ER-positive and HER2-negative. 
• NCT05065411: Efficacy & Safety Evaluation of Enobosarm in Combo With Abemaciclib in Treatment of ER+HER2- Metastatic Breast Cancer. This study will look at the efficacy and safety of a drug known as a Selective Androgen Receptor Modulator (SARM) enobosarm in combination with abemaciclib to treat estrogen receptor-positive (ER+), HER2-negative metastatic breast cancer that tests positive for the presence of androgen receptors.  
• NCT05306340: A Study Evaluating the Efficacy and Safety of Giredestrant Plus Everolimus Compared With Exemestane Plus Everolimus in Participants With Estrogen Receptor-Positive, HER2-Negative, Locally Advanced or Metastatic Breast Cancer (evERA Breast Cancer). This study will evaluate the efficacy and safety of the selective estrogen receptor degrader (SERD) giredestrant, plus everolimus compared with exemestane plus everolimus in people with estrogen receptor ER-positive, HER2-negative locally advanced or metastatic breast cancer who have had previous treatment with a CDK4/6 inhibitor and hormone therapy.
• NCT04546009: A Study Evaluating the Efficacy and Safety of Giredestrant Combined With Palbociclib Compared With Letrozole Combined With Palbociclib in Participants With Estrogen Receptor-Positive, HER2-Negative Locally Advanced or Metastatic Breast Cancer (persevERA Breast Cancer). This study will evaluate the efficacy and safety of the selective estrogen receptor degrader (SERD) giredestrant, combined with palbociclib compared with letrozole combined with palbociclib in patients with ER-positive, HER2-negative locally advanced (recurrent or progressed) or metastatic breast cancer.
• NCT03344965: Olaparib Expanded - Treating Metastatic Breast Cancer in People without gBRCA Mutations. This study will look at whether olaparib is also effective for treating metastatic breast cancer in people who do not have an inherited BRCA mutation. The study is enrolling people with an inherited mutation in PALB2 or an acquired (tumor) mutation in BRCA1 or BRCA2.
• NCT03685331: Olaparib, Palbociclib and Fulvestrant for BRCA-Associated, ER/PR+/HER2-Negative Metastatic Breast Cancer. This study is looking at the side effects and best dose of palbociclib when given with olaparib and fulvestrant for people with HR+/HER2-negative mBC who have a BRCA1 or BRCA2 mutation. 
• NCT04072952: ARV-471 Alone and in Combination With Palbociclib in Patients With ER+/HER2- Locally Advanced or Metastatic Breast Cancer. This is a dose escalation and expansion study to learn the safety and tolerability of ARV-471 alone and combined with palbociclib in people with ER+/HER2- locally advanced or metastatic breast cancer who have received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.
• NCT04448886: Sacituzumab Govitecan +/- Pembrolizumab In HR+ / HER2 - MBC. This research study is evaluating the safety and effectiveness of Sacituzumab Govitecan with or without Pembrolizumab in metastatic HR+/HER2- breast cancer.
• NCT04563507: Combined Immunotherapies in Metastatic ER+ Breast Cancer. Patients receiving standard first-line therapy for metastatic HR+ Breast cancer(BC) (letrozole+palbociclib) are randomly assigned to also receive Stereotactic Body Radiation Therapy(SBRT) to each metastatic lesion.
• NCT04895358: Pembrolizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy for HR+/HER2- Inoperable or Metastatic Breast Cancer (KEYNOTE-B49). The study will look at the safety and efficacy of pembrolizumab plus chemotherapy compared to chemotherapy alone in the treatment of HR+/HER2- locally recurrent inoperable or metastatic breast cancer. 
• NCT04946864: A Study to Investigate the Safety, Tolerability, of APG-2575 as a Single Agent or in Combination for Breast Cancer. This is an open-label study of APG-2575 as a single agent in patients with advanced solid tumors or in combination with anti-cancer agents such as the CDK4/6 inhibitor palbociclib in patients with ER+/HER2- mBC who have progressed or relapsed after first-line therapy.

Other clinical trials for people with breast cancer can be found here.

The following studies are looking at treatment for people with advanced solid tumors. 

• NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced Solid Tumors.This study will test the safety and effectiveness of the experimental drug NUV-868 alone and combined with a PARP inhibitor in people with advanced solid tumors. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
• NCT05169437: PARP inhibitor (niraparib) in patients with inherited or tumor PALB2 mutations in advanced solid tumors (PAVO). PAVO is a Phase II study investigating if the PARP inhibitor niraparib is safe and effective for people with an advanced solid tumor who have an inherited PALB2 gene mutation or a tumor with a PALB2 mutation.
• NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anticancer agents to patients with advanced cancer. The study is enrolling people with inherited mutations, including BRCA1, BRCA2, ATM, RAD51C, RAD51D, and people with tumors that are HRD-positive.  
• NCT04644068: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA). This research is designed to learn whether treatment with a new PARP inhibitor, AZD5305, used alone or in combination with anti-cancer agents is safe, tolerable and has anti-cancer activity in patients with advanced solid tumors. The study is open to people who have previously been treated with PARP inhibitors.  
• NCT04267939: ATR Inhibitor Plus Niraparib Study in Advanced Solid Tumors and Ovarian Cancer. This study will look at how well people with advanced solid tumors respond to treatment with the targeted therapy BAY1895344 in combination with the PARP inhibitor niraparib. This study is open to people with inherited mutations in ATM, BRCA1, BRCA2 and other genes. Contact the study coordinator for information about eligibility for people with mutations in other genes. 
• NCT04657068: Treatment with ATR Inhibitor for Advanced or Metastatic Solid Tumors. This study will look at how well a new oral targeted therapy known as an ATR inhibitor works on advanced or metastatic solid tumors with mutations in genes that are linked to DNA damage repair. This study is open to people who have an inherited or acquired BRCA or ATM mutation or whose tumors are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.