Pharmacoeconomic evaluations of CDK4/6 inhibitors plus endocrine therapy for advanced hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer: a systematic review

Abstract

Background: Hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2−) breast cancer is the most common molecular subtype of breast cancer in many countries, and endocrine therapy remains a mainstay in its treatment. Cyclin-dependent kinase (CDK) 4/6 inhibitors are a new class of targeted agents administered orally that are recommended being used in combination with endocrine therapy as first and second line treatments for advanced HR+/HER2− breast cancer. However, their high prices largely hinder using these drugs in real world settings. To offer a new basis for future research, we investigated the cost-effectiveness of combinations of CDK4/6 inhibitors with endocrine therapy in the treatment of advanced HR+/HER2− breast cancer.Methods: We systematically searched several frequently used databases and identified economic evaluations published from February 2015 to April 2021. The systematic review was performed after retrieving the literatures and extracting data based on inclusion and exclusion criteria. The quality of each selected economic evaluation was assessed by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). Results:The literature search yielded 161 articles, among which fourteen studies (15 articles) with CHEER scores ranging from 58.33% to 87.50% entered the final analysis. Markov models were used in most studies. Based on the currently available data, CDK4/6 inhibitors plus endocrine therapy were less costeffective in first-or second-line treatment of patients with HR+/HER2− advanced breast cancer. However, ribociclib plus letrozole was more cost-effective than palbociclib plus letrozole in the first-line treatment of postmenopausal women. The economic impacts of CDK4/6 inhibitors plus endocrine therapy in nonpostmenopausal patients or second-line therapy cannot be fully evaluated due to the limited number of studies. The three most common factors affecting economic outcomes were the prices of CDK4/6 inhibitors, hazard ratios for progression-free survival and overall survival, and health status utility values. Discussion: CDK4/6 inhibitors plus endocrine therapy have shown significantly improved efficacy outcomes in HR+/HER2− metastatic breast cancer (mBC)/advancer breast cancer (ABC) first-line and second-line treatment for endocrine-sensitive and endocrine-resistant populations, while more potential fields including neoadjuvant and adjuvant settings are being identified to benefit a wider range of breast cancer patients. Meanwhile, risk of severe adverse events that more likely to happen in patients treated with CDK4/6 inhibitors can lead to reduced life quality and higher medical costs patients need to afford. The adverse drug reaction related cost in several economic burden studies were explored to be primarily driven

Therapeutic evolution in HR+/HER2- breast cancer: from targeted therapy to endocrine therapy

“…Breast cancer, which originates in the breast area, can metastasize to other parts such as lymph nodes as tumor progresses ( Zhu et al, 2022 ). The disease is classified into stages I through IV, based on tumor size and the extent of cancer cell dissemination ( Jerzak et al, 2023 ; Pegram et al, 2023 ).…”

“…These treatments are supplemented with endocrine hormone therapy and targeted therapy. For stage IV or metastatic breast cancer, the disease has spread beyond the breast to other tissues or organs via blood or tissue, thereby escalating the complexity of treatment ( Zhu et al, 2022 ; Pegram et al, 2023 ; Torrisi et al, 2023 ). Each year, nearly 41,000 individuals succumb to metastatic breast cancer ( American Cancer Society, 2023 ).…”

Novel Therapeutic Combination Targets the Growth of Letrozole-Resistant Breast Cancer through Decreased Cyclin B1

“…This finding along with others supported the development of cyclin D1-cdk4/6 inhibitors. Currently, for women diagnosed with HER2-negative, hormone-receptor-positive advanced disease, cdk4/6 inhibitors are indicated with endocrine therapy as first-line or second-line treatment [ 8 ] and have shown significantly improved efficacy outcomes [ 9 ]. Unfortunately, cdk4/6 inhibitors are also associated with resistance that can occur through the loss of the retinoblastoma protein (Rb) or phosphatase and tensin homology (PTEN) [ 10 ]; however, some AI-resistant tumors are HER2-positive and are not candidates for cdk4/6 inhibitor treatment.…”

“…Glyceollins are phytoalexins that are composed of three isomers (glyceollin I, glyceollin II, and glyceollin III) that are isolated from activated soy. Previously reports indicate that glyceollin is a novel antiestrogen that binds to the ER and reduces estrogen-induced tumor progression [ 9 ]. When letrozole-resistant cells were treated with glyceollin I, cell proliferation and cell motility were attenuated and the EMT was reversed [ 23 ].…”

Intrinsic subtypes and therapeutic decision-making in hormone receptor-positive/HER2-negative metastatic breast cancer with visceral crisis: A case report

“…The recommendation is based on unprecedented progression-free survival (PFS) improvements, accompanied by a clinically relevant benefit in overall survival (OS), especially with ribociclib, never observed before with standard chemotherapy (CT) and ET regimens (4)(5)(6)(7)(8)(9)(10). However, the addition of a CDKi to ET is associated with more adverse events (AEs), compared with ET alone, as well as significantly higher costs (11)(12)(13). Unfortunately, no clear biomarker exists to help identify patients most benefiting from a CDKi and which one of the three should be the most proper for each single patient, although intrinsic subtypes (IS) might fill the gap (14, 15).…”