OBJECTIVES

The HER2-negative metastatic breast cancer (mBC) treatment landscape has evolved substantially over the last five years, with identification of HER2-low patients, previously classified as HER2-negative, and through EMA approval of novel therapies for HER2-negative patients. Majority of these agents have been assessed for reimbursement by national health technology assessment bodies (HTABs) in EU4 and England. This research investigated whether evidence that became available post-launch mitigated HTAB concerns on the evidence base, to support future access to therapies for HER2-low mBC patients.

METHODS

In lack of approved HER2-low targeting therapies, an in-depth analysis of the HTAs for therapies targeting CDK4/6, PI3K or PARP in HER2-negative mBC was conducted for national HTABs in EU4 and England as a proxy for HER2-low therapies. The analysis for palbociclib, abemaciclib, ribocicblib, alpelisib, talazoparib and olaparib focused on HTAB concerns regarding trial design, clinical outcomes, data maturity, safety and HRQoL. A targeted literature review (TLR) was conducted to identify evidence published post-HTA submission which addressed prioritized HTAB concerns.

RESULTS

Of 53 HTA recommendations, 30% were positive, 23% were positive with restrictions, 17% were negative and 30% received no recommendation. HTABs questioned relevance of progression-free survival (PFS) as primary endpoint, reliability of median PFS as a surrogate for OS and size of subgroups. The TLR identified studies on the association of PFS to other relevant endpoints, real-world studies validating long-term survival projections and studies confirming the treatment response in subgroups, revealing that post-launch data mitigated some payer concerns.

CONCLUSIONS

Majority of HTAB critiques on HER2-negative mBC agents were around study design, selection of endpoints and data maturity and will likely be similar for upcoming HER2-low therapy launches. Our research suggests that some of these uncertainties can be accepted at launch based on post-launch evidence identified, which would accelerate access to patients in areas of high unmet need.