OBJECTIVES

: The SOLAR-1 trial demonstrated combination of alpelisib plus fulvestrant (AF) significantly prolonged median progression-free survival (PFS) relative to monotherapy with fulvestrant (F) for treatment of hormone receptor (HR)-positive, (HER2)-negative advanced breast cancer (ABC) in patients who had previously received endocrine therapy. The objective of this analysis was to assess the cost-effectiveness of this therapy from a US payer perspective.

METHODS

: A Markov model with 3 health states (stable disease, disease progression, death) was constructed to estimate the lifetime cost and effectiveness of the AF combination therapy vs. monotherapy with F in the second-line treatment of ABC. Patient-level simulation was used to model the lifetime course of disease and occurrence of adverse events for patients with ABC. Transition probabilities were estimated based on results from the SOLAR-1 phase-3 clinical trial. Overall survival (OS) data for the AF combination therapy has not matured; thus, we assumed survival after disease progression using OS data from clinical trials of anticipated subsequent-lines of therapy: palbociclib plus fulvestrant (PALOMA-3 trial) and everolimus plus exemestane (BOLERO-2 trial). Direct costs of the therapies, major adverse events, laboratory tests, disease progression, and health utilities were obtained from published sources. The models used 3% discount rate and reported in 2019 US dollars. One-way and probabilistic sensitivity analyses were performed in the study.

RESULTS

: Over a lifetime, patients treated with the AF combination therapy gained 0.43 QALYs compared with monotherapy with fulvestrant regardless of treatment after disease progression with the AF combination therapy. The additional cost of combination therapy was $275,066 or $275,972, resulting in an incremental cost-effectiveness ratio (ICER) of $641,303/QALY or $648,600/QALY assuming patients progress to treatment with either palbociclib plus fulvestrant or everolimus plus exemestane, respectively.

CONCLUSIONS

: Despite significant improvements in PFS, the addition of alpelisib to fulvestrant in the treatment of HR+/HER2- ABC was clearly not cost-effective.