IMforte: Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis of first-line maintenance (1Lm) treatment (Tx) with lurbinectedin (lurbi) + atezolizumab (atezo) vs atezo in extensive-stage small cell lung cancer (ES-SCLC).

Abstract

8086 Background: IMforte (NCT05091567) is the first positive phase 3 study of 1Lm in ES-SCLC to demonstrate statistically significant and clinically meaningful progression-free survival (PFS) and overall survival (OS) benefits (stratified hazard ratios, 0.54 and 0.73) with lurbi + atezo vs atezo. The combination was generally well tolerated based on safety findings and patient-reported outcomes. These data led to the approval of lurbi + atezo as 1Lm Tx for adults with ES-SCLC in the US and Switzerland in 2025. Here, we describe a post hoc Q-TWiST analysis using IMforte data to further elucidate the benefit-risk profile of lurbi + atezo. Methods: Eligible pts with ES-SCLC who were progression free after induction with atezo, carboplatin, and etoposide were randomized 1:1 to receive lurbi + atezo or atezo alone every 3 weeks. Survival time was partitioned into 3 health states: toxicity (TOX; time with grade ≥3 adverse events before disease progression), TWiST (time without TOX before disease progression), and relapse (REL; time from disease progression to death). The mean time spent in each health state was estimated using restricted mean survival times, calculated as area under the Kaplan-Meier curve. Q-TWiST was the sum of the mean time in each health state adjusted by respective utility weights, derived from EQ-5D-5L data. Results: Analyses were performed on all randomized pts from IMforte (lurbi + atezo, n = 242; atezo, n = 241) as of July 29, 2024, with a median follow-up of 15 months (mo). Utility weights in lurbi + atezo and atezo arms were 0.84 and 0.83 in TWiST, 0.83 and 0.83 in TOX, and 0.78 and 0.76 in REL health states. Pts in the lurbi + atezo arm spent most of their survival time in the TWiST state (66% vs 50% for atezo), and their mean duration of TWiST was substantially longer vs the atezo arm (9.8 vs 6.4 mo; Table). Lurbi + atezo arm pts spent more time in the TOX state vs atezo (0.7 vs 0.3 mo) but less time in the REL state (4.4 vs 6.1 mo). The lurbi + atezo arm had longer mean Q-TWiST vs atezo (12.2 vs 10.2 mo), representing a clinically important 14.9% gain in utility at the maximum follow-up of 26 mo. Conclusions: Lurbi + atezo pts had more time without toxicity before disease progression vs atezo and showed a clinically important improvement in quality-adjusted survival, further supporting a favorable benefit-risk profile of lurbi + atezo as 1Lm Tx for ES-SCLC. Clinical trial information: NCT05091567 . Mean duration of each health state, Q-TWiST, PFS, and OS. Mo, Mean (95% CI) Lurbi + Atezon = 242 Atezon = 241 Difference Relative Gain Q-TWiST 12.2 (11.1, 13.2) 10.2 (9.2, 11.3) 1.9 (0.5, 3.4) 14.9% TWiST 9.8 (8.4, 11.2) 6.4 (5.2, 7.7) 3.4 (1.5, 5.2) TOX 0.7 (0.5, 0.9) 0.3 (0.1, 0.5) 0.4 (0.1, 0.6) REL 4.4 (2.8, 6.0) 6.1 (4.6, 7.6) −1.8 (−4.0, 0.4) PFS 10.5 (9.1, 11.9) 6.8 (5.4, 8.1) 3.7 (1.8, 5.6) OS 14.8 (13.5, 16.1) 12.9 (11.6, 14.2) 2.0 (0.1, 3.8)