Impact of systemic delays in targeted therapy (TT) access for advanced NSCLC (aNCSLC) with actionable genomic alterations (AGA+) in Alberta, Canada.

Abstract

e23028 Background: Approval and funding timelines for precision oncology drugs in Canada lag those of other OECD nations. Following proof of efficacy (POE) (clinical trial readout or publication), multiple steps including regulatory review, health technology assessment, price negotiation, and sequential jurisdictional (provincial) funding agreements must be completed before a novel TT is available and funded through the Canadian system. We assessed survival probabilities and potential years of life lost (PYLL) relative to this process among patients who received first-line (1L) palliative-intent TT approved and funded in the last 10 years (afatinib, alectinib, brigatinib, crizotinib, entrectinib, larotrectinib, lorlatinib, osimertinib, and selpercatinib) for an AGA+ aNSCLC diagnosis. Methods: The Alberta Glans-Look Lung Cancer Research (GLR) dataset was used to determine the outcomes (PFS and OS) of two population- level cohorts: 1) AGA+ receiving an approved and funded 1L TT, and 2) AGA- receiving a non-TT (chemotherapy and/or immune checkpoint inhibitor). Outcomes of AGA- patients were considered a proxy for outcomes of AGA+ patients for whom a TT is not available. Average time from POE to public funding in Alberta was determined using clinical trial publications and documentation from Health Canada, Canada’s Drug Agency, pan-Canadian Pharmaceutical Alliance, and the Alberta provincial drug formulary. Probability of survival from POE to funding was estimated using Kaplan-Meier methods. PYLL for both PFS and OS was calculated as the difference in observed time-to-event between the AGA+ and AGA- cohorts multiplied by the median POE to funding interval for 1L-TT. For PFS, this value was further multiplied by the estimated annual number of Alberta AGA+ aNSCLC diagnoses (from Statistics Canada), and for OS by the estimated annual deaths in Alberta from AGA+ aNSCLC (from Brenner et al. 2023; PMID 37999145). Results: 485 AGA- and 529 AGA+ (143 ALK, 337 EGFR, 7 RET, 42 ROS1) patients with aNSCLC receiving a 1L palliative intent systemic therapy were identified from 2015-2025. Average time from POE to public funding in Alberta was 42.9 mo [range: 18 - 71.8 mo]; 31.6, 28.2, 47, and 53 mo for ALK, EGFR, NTRK, RET, and ROS1 1L-TT respectively. Probability of survival to 42.9 months was 41% for AGA+ on 1L-TT and 0% for AGA- receiving non-TT. PYLL during this interval was 993.7 years for PFS and 914.22 years for OS. Conclusions: The time required for novel TT to traverse from POE to public funding in Alberta results in substantial lost years of life. Given these conditions, people living with aNSCLC today are unlikely to survive long enough to access a novel emerging TT in either the 1 st or later treatment lines. Incentivizing regulatory submission directly following POE and streamlining the approval and funding process is a current unmet need to improve equitable TT access and outcomes.