Which medications are used in the adjuvant treatment of breast cancer?

Updated: Dec 27, 2019
  • Author: Pavani Chalasani, MD, MPH; Chief Editor: John V Kiluk, MD, FACS  more...
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In patients receiving adjuvant aromatase inhibitor therapy for breast cancer who are at high risk for fracture, the monoclonal antibody denosumab or either of the bisphosphonates zoledronic acid and pamidronate may be added to the treatment regimen to increase bone mass. These agents are given along with calcium and vitamin D supplementation.

Bevacizumab, a humanized monoclonal antibody that inhibits angiogenesis, had been approved for use in combination therapy for metastatic breast cancer. In November 2011, however, the US Food and Drug Administration (FDA) revoked its approval for this indication, after concluding that bevacizumab had not been shown to be safe and effective for that use. [77]  

In December 2013, Hoffmann-La Roche, manufacturer of capecitabine (Xeloda), an oral agent for the treatment of breast and colorectal cancers, reported that in rare cases, patients using the drug may develop potentially fatal cutaneous disease, such as Stevens-Johnson syndrome or toxic epidermal necrolysis. Signs and symptoms of severe skin reactions may include flu-like symptoms, fever, itching, mouth sores, and burning eyes, as well as a painful, red or purplish rash that causes the skin to shed. [198]

Fulvestrant (Faslodex) was approved by the FDA for hormone receptor (HR)-positive, HER2-negative locally-advanced or metastatic breast cancer in postmenopausal women not previously treated with endocrine therapy.

The approval is based on results from the phase III FALCON trial, a total of 462 treatment-naïve patients were randomly assigned to 500 mg of fulvestrant on days 0, 14, 28 or 1 mg daily of anastrozole. Eligible patients had received no prior endocrine therapy, although treatment with 1 prior chemotherapy. 

Data from FALCON showed that fulvestrant extended median progression-free survival (PFS) by 2.8 months compared with the aromatase inhibitor anastrozole. Overall response rate and clinical benefit rate did not differ significantly between groups. Fulvestrant resulted in a median duration of response of 20 months as compared with 13.2 months with anastrozole. Median duration of clinical benefit was 22.1 months with fulvestrant and 19.1 months with anastrozole. Expected duration of response also favored fulvestrant, as did expected duration of clinical benefit. [199]

Alpelisib (Piqray) is a phosphatidylinositol-3-kinase (PI3K) inhibitor approved by the FDA in May 2019. It is indicated in combination with fulvestrant for treatment of men and postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen. 

Approval for alpelisib was supported by the SOLAR-1 trial (n=572). Results demonstrated that adding alpelisib to fulvestrant significantly prolonged median PFS (11 months) compared with fulvestrant alone (5.7 months) in patients whose tumors had a PIK3CA mutation. [200]

Palbociclib and ribociclib are cyclin-dependent kinases (CDK) 4, 6 inhibitors indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

Approval of palbociclib for initial endocrine-based therapy in postmenopausal women was based on the phase II trial (PALOMA-1) which measured median progression-free survival (PFS) duration. The mean PFS was 10.2 months in the letrozole group and 20.2 months for palbociclib plus letrozole group. [147]

The approval of palbociclib for ER+/HER2- advanced breast cancer in combination with fulvestrant in women (regardless of menopausal status) with disease progression following endocrine therapy was based on the PALOMA-3 trial (n=521). PFS was prolonged with palbociclib plus fulvestrant compared with fulvestrant alone (9.2 mo. vs 3.8 mo.). [201]

Approval of ribociclib was based on interim analysis results from the pivotal phase 3 MONALEESA-2 trial in postmenopausal women who received no prior systemic therapy for their advanced breast cancer. The trial demonstrated that ribociclib plus the aromatase inhibitor letrozole reduced the risk for progression or death compared with letrozole alone. The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63% with a duration of 19.3 months in the ribociclib group and 42.2% with a duration of 14.7 months in the letrozole alone group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively. [148]  Since these data were published, a subsequent analysis with an additional 11 months of follow-up showed that the median PFS was 25.3 months with the ribociclib combination vs 16 months with letrozole alone, according to a company statement.

A third inhibitor, abemaciclib was FDA approved in September 2017. Approval was based on results from the MONARCH 1 and 2 trial. The Monarch 1 trial studied the safety and efficacy of abemaciclib as a stand-alone treatment in a single-arm trial of 132 patients with HR-positive, HER2-negative breast cancer that had progressed after treatment with endocrine therapy and chemotherapy after the cancer metastasized. Abemaciclib was administered at 200 mg orally twice daily until disease progression or unacceptable toxicity. At the 8-month interim analysis, 35.6% of patients had received at least 8 cycles of the CDK4/6 inhibitor.The investigator-assessed, confirmed ORR was 19.7%, which included all partial responses (PR). The rate of patients with stable disease (SD) ≥6 months was 22.7%, leading to a clinical benefit rate of 42.4%. The median time to response was 3.7 months and the median duration of response was 8.6 months. [202]

In February 2018, the FDA also approved this CDK inhibitor for use in combination with an aromatase inhibitor for frontline treatment of postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer. Approval was based on data from the MONARCH 3 trial; a double-blind, randomized phase III study of abemaciclib or placebo plus a nonsteroidal aromatase inhibitor (NSAI) in 493 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had no prior systemic therapy in the advanced setting. The addition of abemaciclib to anastrozole or letrozole reduced the risk of progression or death by 46% compared with the NSAI alone for previously untreated patients with HER2-negative, HR-positive advanced breast cancer. In the study, the median progression-free survival was 28.2 months in the abemaciclib arm versus 14.8 months with the NSAI alone. In those with measurable disease, the ORR was 55.4% with the CDK4/6 inhibitor and 40.2% in the control arm. The median duration of response was 27.4 months for the abemaciclib arm compared with 17.5 months in the control arm. [203]


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