Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial.
Year: 2025
Type: conference-abstract
Abstract: 8006 Background: Despite improved efficacy when adding 1L PD-(L)1 inhibitors to platinum-based chemotherapy for ES-SCLC, long-term survival remains limited. We report primary results from the global open-label, randomized, Phase 3 IMforte study (NCT05091567) of 1L maintenance tx with lurbi + atezo vs atezo in pts with ES-SCLC. Methods: Tx-naive pts with ES-SCLC received standard induction tx with atezo, carboplatin, and etoposide for four 21-day cycles (q3w). After induction, eligible pts without disease progression (PD) were randomized 1:1 to receive maintenance tx q3w with lurbi (3.2 mg/m 2 IV; with G-CSF prophylaxis) + atezo (1200 mg IV) or atezo alone until PD, unacceptable toxicity, or withdrawal. Pts were stratified by liver metastases at induction baseline (BL; yes/no), receipt of prophylactic cranial irradiation before randomization (yes/no), ECOG PS (0/1) and LDH (≤ULN/ > ULN) at maintenance BL. Crossover was not allowed. Primary endpoints were independent review facility (IRF)–assessed PFS per RECIST v1.1 and OS assessed from randomization into the maintenance phase. Results: Of 660 enrolled pts, 483 were randomized to receive lurbi + atezo (n = 242) or atezo (n = 241). BL characteristics were generally balanced between arms. With a median 15.0-mo follow-up (data cutoff: Jul 29, 2024), IRF-PFS was significantly improved with lurbi + atezo vs atezo (stratified HR, 0.54 [95% CI: 0.43, 0.67]; P < 0.0001; Table). A significant OS benefit was seen with lurbi + atezo vs atezo (stratified HR, 0.73 [95% CI: 0.57, 0.95]; P = 0.0174). Median maintenance tx duration was 4.1 mo with lurbi and 4.2 mo with atezo in the lurbi + atezo arm (n = 242) and 2.1 mo in the atezo arm (n = 240). In the lurbi + atezo and atezo arms, respectively, treatment-related AEs (TRAEs) occurred in 83.5% vs 40.0% of pts, G3/4 TRAEs in 25.6% vs 5.8% and G5 TRAEs in 0.8% (2 pts; sepsis, febrile neutropenia) vs 0.4% (1 pt; sepsis); AEs led to tx discontinuation in 6.2% vs 3.3%. Conclusions: IMforte met both primary endpoints of IRF-PFS and OS, demonstrating a clinically meaningful benefit with 1L maintenance tx with lurbi + atezo vs atezo in pts with ES-SCLC. Lurbi + atezo was generally well tolerated, with no new or unexpected safety signals. IMforte is the first global Phase 3 study to show PFS and OS improvement with 1L maintenance tx for ES-SCLC and supports maintenance lurbi + atezo as a new option for pts with this aggressive disease. Clinical trial information: NCT05091567 . Efficacy from randomization into maintenance phase Lurbi + atezo (n=242) Atezo(n=241) IRF-PFS Event, n (%) 174 (71.9) 202 (83.8) Median (95% CI), mo 5.4 (4.2, 5.8) 2.1 (1.6, 2.7) Stratified HR (95% CI) 0.54 (0.43, 0.67); P <0.0001 a ; α=0.001 b OS Event, n (%) 113 (46.7) 136 (56.4) Median (95% CI), mo 13.2 (11.9, 16.4) 10.6 (9.5, 12.2) Stratified HR (95% CI) 0.73 (0.57, 0.95); P =0.0174 a ; α=0.0313 b a Stratified log-rank. b 2-sided boundary.
Source: Journal of Clinical Oncology
Authors: Luis G. Paz-Ares, Hossein Borghaei, Stephen V. Liu, Solange Peters, Roy S. Herbst, Katarzyna Magdalena Stencel, Margarita Majem, Grzegorz Czyżewicz, Reyes Bernabe Caro, Ki Hyeong Lee, Melissa Lynne Johnson, Nuri Karadurmus, Christian Grohe, Vaikunth Cuchelkar, Vilma Graupner, Monika Dulloo Kaul, Ya-Chen Lin, Debasis Chakrabarti, Kamalnayan Bhatt, Martin Reck
Institutions: Universidad Complutense de Madrid, Hospital Universitario 12 De Octubre, Fox Chase Cancer Center, Georgetown University, Centre Hospitalier Universitaire Vaudois, Yale Cancer Center, Hospital de Sant Pau, John Paul II Hospital, Hospital Universitario Virgen del Rocío, Chungbuk National University, Chungbuk National University Hospital, Tennessee Oncology, Sağlık Bilimleri Üniversitesi, Evangelische Lungenklinik Berlin, Genentech, Roche (Switzerland), Jazz Pharmaceuticals (Ireland), LungenClinic Grosshansdorf
Language: English
Topic: Lung Cancer Research Studies
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Genentech
OpenAlex ID: W4410820847