Challenges in Projecting Treatment Journeys for ALK-mutated NSCLC: Addressing Uncertainty in PPS and Immature Overall Survival Data
Author(s)
Rahyssa R. Sales1, Bruna Carvalho Silva, Sr., MD2, Rafael Duarte Paes, BSc2, Rodrigo Dienstmann, PhD, MD2, Deborah Marta dos Santos Oliveira, MSc2, Mariana Tosello Laloni, PhD, MD2, Ana Caroline Zimmer Gelatti, PhD, MD2, William Nassib William Junior, PhD, MD2, Carlos Gil Moreira Ferreira Gil, PhD, MD2, Pedro Nazareth Aguiar Junior, PhD, MD2.
1Biologist, Grupo Oncoclínicas, Belo Horizonte, Brazil, 2Oncoclínicas&Co/MedSir, São Paulo, Brazil.
1Biologist, Grupo Oncoclínicas, Belo Horizonte, Brazil, 2Oncoclínicas&Co/MedSir, São Paulo, Brazil.
Presentation Documents
OBJECTIVES: In ALK-mutated stage IV Non-Small Cell Lung Cancer (NSCLC), randomized clinical trials (RCTs) often provide immature overall survival (OS) data, leading to challenges in predicting long-term outcomes. The gap between progression-free survival (PFS) and OS with first-line tyrosine kinase inhibitors (TKIs) complicates post-progression survival (PPS) assessments, especially when treatment patterns are unclear. This "grey area" poses difficulties for economic modeling. Real World Evidence (RWE) can help address these gaps, but its use in health technology assessment (HTA) presents challenges. We aimed to evaluate the incorporation of RWE to address the PPS using data from 126 patients with ALK-mutated stage IV NSCLC from Oncoclínicas&Co/MedSir, Brazil between 2007 and 2024.
METHODS: We analyzed RCTs and RWE for patients with ALK-mutated stage IV NSCLC treated with third-generation TKIs: lorlatinib, alectinib, and brigatinib. We estimated PFS and OS curves from RCTs (CROWN, ALEX, and ALTA-1) and RWE (imputed data) over 20 and 30 years using an exponential distribution.
RESULTS: First-line PFS was 34.8 months (RCT) vs. 16.3 months (RWE) for alectinib and 24 months (RCT) vs. 25.9 months (RWE) for brigatinib. First-line PPS was similar across treatments. The PFS for the second TKI was 6.6 months (RCT) and 24.9 months (RWE). For post-TKI chemotherapy, PFS was 3 months (RCT) and 2.4 months (RWE). Estimated PPS was 45.9 months (RCT) and 39 months (RWE) for alectinib, and 39.9 months (RCT) and 18.1 months (RWE) for brigatinib, with lorlatinib showing the lowest PPS at 1.3 months (RCT). Limitations include reliance on immature data and the challenge of distinguishing treatment lines in real-world settings. The 'grey area' is the biggest part of the journey for many patients.
CONCLUSIONS: The lack of a defined PPS standard and immature OS data increases uncertainty in treatment projections. While RWE mitigates gaps, robust sensitivity analyses remain critical to account for variability in post-progression outcomes.
METHODS: We analyzed RCTs and RWE for patients with ALK-mutated stage IV NSCLC treated with third-generation TKIs: lorlatinib, alectinib, and brigatinib. We estimated PFS and OS curves from RCTs (CROWN, ALEX, and ALTA-1) and RWE (imputed data) over 20 and 30 years using an exponential distribution.
RESULTS: First-line PFS was 34.8 months (RCT) vs. 16.3 months (RWE) for alectinib and 24 months (RCT) vs. 25.9 months (RWE) for brigatinib. First-line PPS was similar across treatments. The PFS for the second TKI was 6.6 months (RCT) and 24.9 months (RWE). For post-TKI chemotherapy, PFS was 3 months (RCT) and 2.4 months (RWE). Estimated PPS was 45.9 months (RCT) and 39 months (RWE) for alectinib, and 39.9 months (RCT) and 18.1 months (RWE) for brigatinib, with lorlatinib showing the lowest PPS at 1.3 months (RCT). Limitations include reliance on immature data and the challenge of distinguishing treatment lines in real-world settings. The 'grey area' is the biggest part of the journey for many patients.
CONCLUSIONS: The lack of a defined PPS standard and immature OS data increases uncertainty in treatment projections. While RWE mitigates gaps, robust sensitivity analyses remain critical to account for variability in post-progression outcomes.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
RWD94
Topic
Real World Data & Information Systems
Disease
SDC: Oncology