Problem Statement: As early stage intervention with curative intent, the neoadjuvant treatment (NAT) of HER2-positive breast cancer with pertuzumab (P) in combination with trastuzumab (H) lacks mature survival data; hence, it represents excellent example of disconnection between different demands of regulatory and HTA agencies. In line with that, Czech HTA agency (SUKL) initially refused predictive value of pCR for survival and concluded that the evidence provided was insufficient to prove clinical efficacy of P+H combination compared to single-agent therapy in the (neo)adjuvant setting.

Description: In three consecutive evaluations during 2015-2022, increasing amount of evidence, together with strong support of the medical association, eventually led to reconsideration of SUKL´s evaluation. Statement of the Czech Oncology Society, in which it emphasized the significant prognostic role of pCR in current clinical practice was important decisive moment as it also helped with the consolidation of both NAT and adjuvant therapy (AT) into a single therapeutic unit. Final evaluation was based mainly on an updated pooled analysis by Swain et al. For patients with pCR, the pooled analysis demonstrated not only significant improvement in invasive disease-free survival compared to non-pCR patients treated with HER2+-targeted therapy, but also quantified benefit of P+H vs H in these patients when used in both NAT and AT. Positive clinical evaluation enabled acceptation of the cost-effectiveness model and eventually led to the reimbursement of P+H combination in this indication.

Lessons Learned: Acceptance of predictive value of pCR by SUKL represents an important step for patient access also to the other upcoming early-stage cancer therapies. This case is showing how agency´s requirements and opinions were leveraged and what evidence was collected that eventually led to the acceptance of the predictive value of pCR and of comparative clinical efficacy of P+H combination in NAT.

Stakeholder perspective: Industry.