Giuseppe Banna, Consultant Medical Oncologist at Portsmouth Hospitals University NHS Trust, shared a post on LinkedIn:
“Timing, Targets, and the Survival Gap: Lessons from the BR.31 Adjuvant Trial
The publication of the Canadian Cancer Trials Group BR.31 trial in Journal of Clinical Oncology, provides a critical moment for reflection in Thoracic Oncology. While Durvalumab has been a “game-changer” in consolidation settings (PACIFIC and ADRIATIC), it did not meet its primary endpoint in the completely resected NSCLC setting.
The Data at 60 Months: Despite long-term follow-up, adjuvant Durvalumab showed no significant benefit:
DFS (Disease-Free Survival): HR 0.93 (p=0.64).
OS (Overall Survival): HR 0.96 (95% CI 0.71–1.30).
My Key Takeaway:
1. Inter-class and Intra-class Heterogeneity. This negative result highlights a fundamental question: Are all checkpoints created equal?
– Inter-class differences (PD-1 vs. PD-L1): We are seeing a divergence in the adjuvant setting. While Pembrolizumab (anti-PD-1) showed a DFS benefit regardless of PD-L1 status in KEYNOTE-091, the anti-PD-L1 agents have shown more varied results, with Atezolizumab showing its strongest signal only in high-expressors (IMpower010).
– Intra-class nuances: Even within the same class (anti-PD-L1), molecules behave differently. Durvalumab’s failure in BR.31 contrasts with Atezolizumab’s success in IMpower010. This suggests that binding affinity, dosing schedules, or perhaps the specific interaction with the tumor microenvironment post-surgery varies significantly between these agents.
2. Selection Matters: Unlike IMpower010, which showed a clear OS benefit (HR 0.71) in the PD-L1 ≥50% subgroup, BR.31 saw no separation of curves regardless of PD-L1 expression.
The “Clinical So-What?”: We cannot assume “class effects” when moving from metastatic to adjuvant settings. The failure of BR.31 reinforces that molecule selection and patient stratification (beyond just PD-L1 %) are key.
For now, the adjuvant standard remains firmly with Atezolizumab (for high expressors) or Pembrolizumab.
Understanding these pharmacological nuances is what separates a standard treatment plan from true precision medicine.”
Title: Adjuvant Durvalumab in Completely Resected Early-Stage Non–Small Cell Lung Cancer
Authors: Glenwood D. Goss, Gail E. Darling, Virginie Westeel, Kazuhiko Nakagawa, Bartomeu Massutí, Francesco Perrone, Sue-Anne McLachlan, Jin Hyoung Kang, Yi-Long Wu, Anne-Marie C. Dingemans, Rafal Dziadziuszko, Laurent Greillier, Morihito Okada, Clarisse Audigier-Valette, Shunichi Sugawara, Ernest Nadal, Annamaria Catino, Anne-Claire Toffart, Tetsuya Mitsudomi, Renaud Whittom, Manuel Domine, Nobuyuki Yamamoto, Olivier Molinier, Franck Morin, Penelope A. Bradbury, Martin R. Stockler, Keyue Ding, Christopher J. O’Callaghan
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