Combination Therapies: Two Is Company but Is Three (OR MORE) a Concern?
Author(s)
Florez Cespedes M1, Vaid K2, Rube M2, Yan W2
1Trinity, London, LON, UK, 2Trinity, New York, NY, USA
Presentation Documents
OBJECTIVES:
Combination therapies are becoming increasingly common, including triplet and quadruplet regimens, which can increase potential efficacy, but also raise toxicity concerns. The objective of this analysis is to understand how safety criteria is weighted throughout the HTA assessment process and determine whether payers and HTA bodies believe the added clinical benefits of combination regimens outweigh the risks, using Non-Small Cell Lung Cancer (NSCLC) and Multiple Myeloma (MM) as case studies.METHODS:
HTA reports were analyzed in FRA, DEU, and GBR to compare the HTA outcome rationales of doublet/triplet regimens and triplet/quadruplet regimens. The rationales were compared by assessing changes in efficacy outcomes, such as OS, PFS, and safety/tolerability, including AE occurrences and QoL, to understand how decision-making committees prioritize various safety criteria when deciding HTA outcomes.RESULTS:
Due to the familiarity of HTA bodies with chemotherapies, there was limited concern around the management of associated toxicities for doublets/triplet regimens with chemotherapy backbones. However, there was greater HTA scrutiny of safety and QoL for regimens containing multiple immune-oncology agents, which resulted in instances of HTA benefit downgrades (e.g., Nivolumab-ipilimumab-cis/carboplatin for NSCLC in GBR and FRA). Moreover, combination therapies do not always translate to deteriorated QoL; with safety concerns eased for multi-component regimens associated with improved QoL (e.g., pembrolizumab-pemetrexed-carboplatin for NSCLC in GBR and DEU) or significantly improved efficacy (e.g., daratumumab-bortezomib-melphalan-prednisone for MM in FRA). The quadruplet combination in NSCLC was scrutinized the most regarding safety across markets; the combination's moderate efficacy improvement was overshadowed by its safety profile, so access was limited based on patient fitness.CONCLUSIONS:
While superior efficacy compared to trial comparators seems to remain the predominant driver of positive HTA outcomes, safety and QoL profiles are scrutinized across triplet/quadruplet regimens. Payer expectations may be higher for demonstrating clinically meaningful efficacy, particularly if there are detrimental QoL impacts.
Conference/Value in Health Info
2022-05, ISPOR 2022, Washington, DC, USA
Value in Health, Volume 25, Issue 6, S1 (June 2022)
Code
HTA53
Topic
Clinical Outcomes, Health Technology Assessment
Topic Subcategory
Clinical Outcomes Assessment, Decision & Deliberative Processes
Disease
Oncology