Cost-effectiveness of full coverage of aromatase inhibitors for Medicare beneficiaries with early breast cancer

The third-generation AIs are a welcome additional option for the endocrine therapy of hormone receptor-positive breast cancer in postmenopausal women. While nonsteroidal AIs are more effective than tamoxifen for the treatment of advanced disease, the absolute reduction in relapse-free survival for adjuvant AIs over tamoxifen is modest, and the results of several other large adjuvant trials are currently pending. Since there is currently no evidence that the use of an AI increases the number of patients cured of their disease, we consider the impact of AI therapy to be relatively modest, at least for the moment.

Study Approval

  • No dose adjustment is necessary for patients with renal or liver impairment or elderly patients.
  • Preclinical data in resistance models demonstrated that the crosstalk between ER and other signaling pathways particularly MAPK and PI3K/Akt is an important resistant mechanism.
  • Our results demonstrate women are prepared to engage in primary treatments despite their known side-effects and challenges, but AHT caught many off guard.
  • New financing models have been developed, some of which incorporating real-world drug performance (especially drug effectiveness) based on post-marketing health technology assessment (HTA) 2, 3.

The first and most successful targeted cancer therapies are those that target estrogen signaling pathway in breast cancer. Approximately three quarter of breast cancer tumors express hormone receptors like ER and/or progesterone receptors (PR). By modulating either its ligand or the receptor, this strategy has been shown to be effective in treating hormone receptor-positive breast cancer for over a century. In 1890s, Sir George Beatson demonstrated that the majority of breast cancers in premenopausal women respond to bilateral oophorectomy. At that time, it was hypothesized that most of the breast cancer tumors were dependent on “ovarian hormones” 6, 7. Subsequently, other surgical modalities like adrenalectomy and hypophysectomy were also performed for the treatment of breast cancer 7.

Palbociclib and ribociclib, with an aromatase inhibitor, are the appropriate comparators

The primary outcome of the model was the incremental cost-effectiveness ratio (ICER), which is the incremental cost per additional quality-adjusted life year (QALY) gained. The ICER was calculated by comparing the costs and QALYs of each of the three CDK4/6 inhibitors plus letrozole to letrozole alone as a first step. Then the model was re-run to compare the ICERs among the three different CDK4/6 inhibitors plus letrozole in comparison to each other.

As this is an emerging topic with limited literature and a paucity of studies, many articles found provided background rather than specific information on our research topic. Based on these promising results of superiority of AIs over tamoxifen and approximately 50% reduction in the risk of contralateral breast cancer demonstrated by ATAC trial 49, AIs are being investigated as chemopreventive agents for breast cancer. Two large phase III trials are currently ongoing to evaluate this aspect including the IBIS II trial in Europe and the MAP-3 trial in Canada. As anagent to induce ovulation, dosing is 2.5 mg to 5 mg daily for 5 days starting on day 3 of the menstrual cycle. In patients with cirrhosis of the liver, CHild-Pugh Class C, increase the dosing interval to every 48 hours. Oestrogen is known to affect blood lipids, with levels of HDL cholesterol increasing and LDL cholesterol decreasing with rising levels of oestrogen.

Both of the trials did not show statistically significant differences in DFS between AI alone group and tamoxifen sequenced with an AI group as well as an AI sequenced with tamoxifen group in BIG 1–98. However, there appears to be more early relapses in the tamoxifen followed by letrozole group comparing to upfront AI group particularly in women with lymph node involvement 51. The most commonly used AI was anastrozole (39%), followed by letrozole (36%) and exemestane (17%). Published CEAs comparing AIs to tamoxifen inadequately investigate uncertainty to overcome the limitations of translating RCT findings to real-world practice, potentially leading to suboptimal guidance for clinical and health policy decision-making. The implications of these findings extend beyond hormonal therapies for early stage breast cancer to other cancer therapies and drug therapies in general. Care must be taken when interpreting CEAs based on RCTs which employ surrogate endpoints with populations that differ from the real-world population.

The authors concluded that letrozole was not superior to clomiphene ovulation induction in combination with a timed intrauterine insemination in patients with mild to moderate endometriosis, who did not conceive within 6-12 months of laparoscopic surgery. 3.4 Progression-free survival in MONARCH 3 was assessed by the investigators and by independent review. In the final investigator-assessed progression-free survival analysis, median progression-free survival was 28.18 months for abemaciclib and 14.76 months for placebo (hazard ratio HR 0.540, 95% confidence interval CI 0.418 to 0.698). In the final independent review, median progression-free survival was not reached for abemaciclib and was 19.36 months for placebo (HR 0.465, 95% CI 0.339 to 0.636). The ERG raised concerns that the investigator review may not be the most objective outcome measure because of the high incidence of diarrhoea and potential unblinding for abemaciclib. However, it noted that independent-review results are usually more conservative than investigator assessment, which was not the case in MONARCH 3.

Data collection and analysis

This signifies that the ER signaling cascades continue to be an active driving force in AI resistant tumors despite the loss if its expression as discussed below. QoL may be severely affected, with 8% of patients discontinuing treatment due to alopecia and 17% reporting EIA to be the most traumatic dAE during treatment (Ferreira et al., 2019; Freites-Martinez et al., 2018; 2019; Trüeb, 2018). Minoxidil, which facilitates hair growth by increasing the duration of the anagen phase of hair follicles, has led to improvement of EIA in up to 80% of patients (Ferreira et al., 2019; Freites-Martinez et al., 2018; 2019; Lacouture and Sibaud, 2018; Trüeb, Bodbol XBS 250mg/ml (10ml) buy 2018).