LBA 05 - Chemoradiotherapy (CRT) Followed By Consolidation Durvalumab (D) In Patients (pts) with Resectable or Borderline Resectable Stage IIB-IIIB NSCLC Who Become Unresectable during Neoadjuvant Treatment (Tx): Results from the Phase 2 MDT-Bridge Study
Presenter(s)
A. R. Filippi1, M. Reck2,3, C. M. Gay4,5, E. Nadal6, N. Girard7, J. Spicer8, L. W. Martin9, D. A. Cairns10, N. Farre11, E. D’Angelo12, A. Alvarez Gonzalez13, M. J. Kucharczyk14, B. Roch15, A. Boyer16, E. A. Uribelarrea17, L. Li18, I. Diaz Perez19, N. Georgoulia19, M. Giaj Levra20, and C. Petersen21; 1Radiation Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori and Department of Oncology, University of Milan, Milan, Italy, 2LungenClinic Grosshansdorf, Airway Research Center North (ARCN), member of the German Center for Lung Research (DZL), Grosshansdorf, Germany, 3Lung Clinic Großhansdorf, Airway Research Center North, German Center for Lung Research, Großhansdorf, Germany, 4Department of Thoracic-Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5University of Texas MD Anderson Cancer Center, Houston, TX, 6Medical Oncology Department, Institut Català d’Oncologia - ICO Hospitalet, IDIBELL, Barcelona, Spain, 7Institut du Thorax Curie Montsouris, Institut Curie/UVSQ, Paris, France, 8Department of Thoracic Surgery, McGill University, Montreal, QC, Canada, 9Department of Surgery, Division of Thoracic Surgery, University of Virginia, Charlottesville, VA, 10Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom, 11Department of Radiation Oncology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain, 12Radiation Oncology Department, Azienda USL of Bologna, Bologna, Italy, 13Medical Oncology Department, Hospital Universitario Gregorio Marañón, Madrid, Spain, 14Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, ON, Canada, 15Centre Hospitalier Universitaire de Montpellier, Université de Montpellier, Montpellier, France, 16Hôpital Saint Joseph, Marseille, France, 17Medical Oncology Department, Hospital Universitario de Cruces, Barakaldo, Spain, 18AstraZeneca, Mississauga, ON, Canada, 19AstraZeneca, Gaithersburg, MD, 20AstraZeneca, Wilmington, DE, 21Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Purpose/Objective(s):
In PACIFIC (NCT02125461), consolidation D significantly improved PFS and OS in pts with unresectable stage III NSCLC after definitive CRT. In AEGEAN (NCT03800134), perioperative D + neoadjuvant (neoadj) CT vs neoadj CT alone significantly improved pCR and EFS in pts with resectable NSCLC. The phase 2 MDT-BRIDGE study (NCT05925530) is investigating perioperative D + neoadj CT in pts with resectable/borderline resectable NSCLC and outcomes with curative-intent CRT followed by consolidation D in pts deemed unresectable after neoadj Tx. Here, we report results for pts who became unresectable in MDT-BRIDGE.Materials/Methods:
MDT-BRIDGE is a global non-randomized study in Tx-naïve pts with EGFR/ALK wild-type, stage IIB–IIIB NSCLC. After baseline (BL) multidisciplinary team (MDT) resectability assessment, pts received 2 cycles of neoadj D + CT Q3W IV. The MDT then reassessed pts; pts deemed resectable received 1–2 additional cycles of neoadj D + CT then surgery and pts deemed unresectable received SoC CRT for ~6 wk. After surgery/CRT, all pts received adjuvant/consolidation D Q4W IV for up to 1 yr.Results:
As of Jan 12, 2026, 142 pts had received neoadj Tx of whom 50 (35.2%) were deemed borderline resectable at BL. Among all pts, the resection rate (primary endpoint) was 74.6% and CRT Tx rate was 17.6% (Table). At MDT reassessment (after the first 2 neoadj D + CT cycles), 21 pts were deemed unresectable, 18 (85.7%) of whom received CRT; 7 of 121 (5.8%) pts deemed resectable also received CRT after completing 1–2 additional neoadj D + CT cycles; overall, 25 pts received CRT (21 concurrent and 4 sequential). The mean (SD) RT dose was 61.9 (4.2) Gy, and median (range) number of RT fractions was 30.0 (25–33). Among CRT-treated pts, 84.0% had post-CRT objective response (n=13) or stable disease (n=8) (BL defined by the last scan before MDT reassessment), supporting eligibility for consolidation D, received by 23 pts (92.0%). The 12-mo PFS rate (95% CI) was 85.0% (59.8–95.0) for CRT-treated pts, with PFS defined from the first D Tx dose. During CRT, 7 (28.0%) pts had max grade 3/4 AEs, only 1 (4.0%) had an AE leading to discontinuation, 1 (4.0%) had an immune-mediated AE, and 2 (8.0%) had grade 2 pneumonitis. During consolidation D, 4 (17.4%) pts had max grade 3/4 AEs, 3 (13.0%) had AEs leading to discontinuation, 3 (13.0%) had immune-mediated AEs, and 2 (8.7%) had grade 2 pneumonitis.Conclusion:
Among pts unresectable after neoadj Tx, preliminary efficacy outcomes with CRT and consolidation D were promising with a manageable safety profile, supporting use of the PACIFIC regimen in this subgroup.| All patients (N=142) | Borderline resectable at BL (n=50) | Resectable at BL (n=92) | |
| Resection rate, n (%; 95% CI)a | 106 (74.6; 66.7–81.6) | 31 (62.0; 47.2–75.3) | 75 (81.5; 72.1–88.9) |
| Received CRT, n (%) | 25 (17.6) | 12 (24.0) | 13 (14.1) |
| No local Tx, n (%) | 11 (7.7) | 7 (14.0) | 4 (4.3) |
| aBased on patients who started resection, and CIs calculated by Clopper-Pearson exact method. | |||