Neoadjuvant tislelizumab (TIS) plus chemotherapy (CT) with adjuvant TIS vs. neoadjuvant placebo (PBO) plus CT with adjuvant PBO in resectable non-small cell lung cancer (NSCLC): patient-reported outcomes (PRO) in the RATIONALE-315 trial

BackgroundIn the pivotal phase III RATIONALE-315 trial (NCT04379635) of patients with resectable stage II to IIIA NSCLC, perioperative TIS plus (+) neoadjuvant platinum-based CT led to a significant improvement in event-free survival [HR=0.56, p=0.0003] compared to placebo + neoadjuvant platinum-based CT. Here, we report results for PRO instruments from RATIONALE-315.MethodsPROs were secondary endpoints assessed using the EORTC QLQ-C30 and QLQ-LC13 instruments. Key PRO endpoints included QLQ-C30 GHS/QoL, physical function, as well as QLQ-LC13 symptoms of dyspnea, cough, and chest pain. A mixed model for repeated measures was performed at Cycle 1 (baseline), Cycle 3 of neoadjuvant phase, the Cycles 3 and 7 of adjuvant phase. Time to deterioration (TTD) was examined using Kaplan-Meier method. All HRQoL analysis were performed on the intent-to-treat analysis set.ResultsA total of 453 pts were randomized (1:1) to receive neoadjuvant TIS (n=226) or PBO (n=227). By Cycle 7, no meaningful differences in least-squares (LS) mean change from baseline between arms were observed for GHS/QoL, physical functioning, and fatigue, or chest pain and dyspnea (Table); however, the TIS + CT arm experienced a meaningful improvement in LS mean for coughing (-4.37 [95% CI: -9.46 to 0.21]). TTD analysis showed that pts in the TIS + CT arm were at lower risk of worsening for chest pain (HR 0.59 [95% CI: 0.38-0.91]); risk of worsening was similar between the arms in all other PRO endpoints. Table: 1213P HRQoL endpoint Least squares mean (95% CI) Cycle 3: Adjuvant phase Cycle 7: Adjuvant phase TIS PBO TIS PBO QLQ-C30 GHS/QoL -1.14 (-3.79, 1.52) -1.97 (-4.77, 0.83) 1.09 (-1.34, 3.53) 1.90 (-0.66, 4.46) Physical functioning -3.57 (-5.10, -2.05) -3.61 (-5.22, -2.01) -2.60 (-4.20, 1.00) -2.23 (-3.92, -0.54) Fatigue 2.52 (0.23, 4.81) 2.97 (0.57, 5.37) 2.54 (0.09, 4.99 2.87 (0.30, 5.45) QLQ-LC13 Coughing -4.58 (-7.75, -1.42) -5.63 (-8.97, -2.29) -12.15 (-15.60, -8.71) -7.52 (-11.16, -3.89) Chest pain 0.43 (-2.42, 3.28) 5.42 (2.39, 8.44) 0.36 (-2.34, 3.05) 1.89 (-0.96, 4.75) Dyspnea 4.62 (2.57, 6.67) 6.57 (4.41, 8.74) 3.18 (0.82, 5.55) 4.56 (2.07, 7.06) ConclusionsPts in the TIS + chemo arm experienced better HRQoL outcomes than those in the PBO + CT arm in this population of patients with resectable NSCLC, with improvements in coughing and lower risk of chest pain.Clinical trial identificationNCT04379635.Editorial acknowledgementMedical writing support, under the direction of the authors, was provided by Jason C. Allaire, PhD of Generativity Solutions Group, and was funded by BeiGene. Editorial and submission support was provided by Envision Pharma Inc., and funded by BeiGene.Legal entity responsible for the studyBeiGene, Ltd.FundingBeiGene, Ltd.DisclosureF. Cappuzzo: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, GALECTO and MSD; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD. S. Wang, B. Yao, G. Barnes: Financial Interests, Personal, Full or part-time Employment: BeiGene; Financial Interests, Personal, Stocks/Shares: BeiGene. B. Barnes: Financial Interests, Personal, Full or part-time Employment: BeiGene. All other authors have declared no conflicts of interest.