Recurrent Patient-Reported Outcome (PRO)-Based Symptomatic Deterioration Predicts Survival and Disease Progression in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC): Post-Hoc Analysis of RATIONALE-315
Author(s)
Dongsheng Yue, MD1, Changli Wang, MD2, Federico Cappuzzo, MD3, Hongxu Liu, MD4, Qixun Chen, MD5, Shengfei Wang, MD6, Shiang Jiin Leaw, MD6, Bryant Barnes, NA7, Gisoo Barnes, PhD7, Timothy Victor, PhD8.
1Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 2Tianjin Medical University Cancer Institue and Hospital, Tianjin, China, 3Istituto Nazionale Tumori IRCCS Regina Elena, Roma, Italy, 4Liaoning Cancer Hospital and Institute, Shenyang, China, 5Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China, 6BeiGene, Shanghai, China, 7BeiGene, San Mateo, CA, USA, 8Beigene, Ltd, San Mateo, CA, USA & University of Pennsylvania, Philidelphia, PA, USA.
1Tianjin Medical University Cancer Institute and Hospital, Tianjin, China, 2Tianjin Medical University Cancer Institue and Hospital, Tianjin, China, 3Istituto Nazionale Tumori IRCCS Regina Elena, Roma, Italy, 4Liaoning Cancer Hospital and Institute, Shenyang, China, 5Department of Thoracic Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, China, 6BeiGene, Shanghai, China, 7BeiGene, San Mateo, CA, USA, 8Beigene, Ltd, San Mateo, CA, USA & University of Pennsylvania, Philidelphia, PA, USA.
Presentation Documents
OBJECTIVES: Traditional time-to-deterioration analyses do not account for the recurrent nature of PRO symptoms like dyspnea (a common NSCLC symptom). Here, we report results from a 3-component joint model (JM) analysis of the phase 3 RATIONALE-315 study (NCT04379635) that integrates longitudinal and time-to-event data to quantify the association between PROs, survival, and disease progression.
METHODS: RATIONALE-315 was a randomized, double-blind study of perioperative tislelizumab vs placebo, plus neo-adjuvant chemotherapy, in patients with resectable NSCLC. In this post-hoc analysis, a 3-component JM assessed the association between PRO dyspnea scores (by linear mixed model [LMM]), dyspnea symptom deterioration events (by recurrent events [REs] frailty Cox model), and terminal events (TEs; by Cox proportional hazards model).
RESULTS: Of 453 randomized patients, 211 in the tislelizumab arm and 208 in the placebo arm were included in this analysis. Per the LMM component, tislelizumab was associated with a non-substantial dyspnea improvement, with an estimated effect (95% CI) of 2.28 (0.41, 4.17) and P-value of 0.0183. Furthermore, the tislelizumab-by-day interaction indicated a protective effect of tislelizumab on dyspnea over time (estimate [95% CI] −0.01 [−0.02, 0.00]; P=0.0010). In TE analyses, tislelizumab showed a 54% reduction in risk of a TE (thus a higher chance of event-free survival), with an estimate of −0.79 (95% CI: −1.49, −0.23; P=0.0044). Although the REs frailty Cox model was not significant, it suggested a potential association between recurrent dyspnea symptom deterioration and the risk of TEs (estimate [95% CI] 3.81 [−1.64, 7.30], P=0.1495), corresponding to a hazard ratio of 44.96.
CONCLUSIONS: These data demonstrated that patient-reported deterioration of dyspnea symptoms over time may be a predictor of clinically important survival events (based on TEs). Furthermore, dyspnea appears to improve with tislelizumab compared with placebo. Modeling can highlight the importance of PROs as a prognostic tool in the journey of patients with cancer.
METHODS: RATIONALE-315 was a randomized, double-blind study of perioperative tislelizumab vs placebo, plus neo-adjuvant chemotherapy, in patients with resectable NSCLC. In this post-hoc analysis, a 3-component JM assessed the association between PRO dyspnea scores (by linear mixed model [LMM]), dyspnea symptom deterioration events (by recurrent events [REs] frailty Cox model), and terminal events (TEs; by Cox proportional hazards model).
RESULTS: Of 453 randomized patients, 211 in the tislelizumab arm and 208 in the placebo arm were included in this analysis. Per the LMM component, tislelizumab was associated with a non-substantial dyspnea improvement, with an estimated effect (95% CI) of 2.28 (0.41, 4.17) and P-value of 0.0183. Furthermore, the tislelizumab-by-day interaction indicated a protective effect of tislelizumab on dyspnea over time (estimate [95% CI] −0.01 [−0.02, 0.00]; P=0.0010). In TE analyses, tislelizumab showed a 54% reduction in risk of a TE (thus a higher chance of event-free survival), with an estimate of −0.79 (95% CI: −1.49, −0.23; P=0.0044). Although the REs frailty Cox model was not significant, it suggested a potential association between recurrent dyspnea symptom deterioration and the risk of TEs (estimate [95% CI] 3.81 [−1.64, 7.30], P=0.1495), corresponding to a hazard ratio of 44.96.
CONCLUSIONS: These data demonstrated that patient-reported deterioration of dyspnea symptoms over time may be a predictor of clinically important survival events (based on TEs). Furthermore, dyspnea appears to improve with tislelizumab compared with placebo. Modeling can highlight the importance of PROs as a prognostic tool in the journey of patients with cancer.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
PCR97
Topic
Patient-Centered Research
Topic Subcategory
Patient-reported Outcomes & Quality of Life Outcomes
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology