Related Experiment Video
Updated: Sep 5, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
Comprehensive Genome Profiling in Patients With Metastatic Non-Small Cell Lung Cancer: The Precision Medicine Phase
Fabrice Barlesi1,2, Pascale Tomasini2, Maryam Karimi3,4
1Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Purpose:
Targeted therapies (TT) and immune checkpoint blockers (ICB) have revolutionized the approach to non-small cell lung cancer (NSCLC) treatment in the era of precision medicine. Their impact as switch maintenance therapy based on molecular characterization is unknown.
Patients And Methods:
SAFIR02-Lung/IFCT 1301 was an open-label, randomized, phase II trial, involving 33 centers in France. We investigated eight TT (substudy-1) and one ICB (substudy-2), compared with standard-of-care as a maintenance strategy in patients with advanced EGFR, ALK wild-type (wt) NSCLC without progression after first-line chemotherapy, based on high-throughput genome analysis. The primary outcome was progression-free survival (PFS).
Results:
Among the 175 patients randomized in substudy-1, 116 received TT (selumetinib, vistusertib, capivasertib, AZD4547, AZD8931, vandetanib, olaparib, savolitinib) and 59 standard-of-care. Median PFS was 2.7 months [95% confidence interval (CI), 1.6-2.9] with TT versus 2.7 months (1.6-4.1) with standard-of-care (HR, 0.97; 95% CI, 0.7-1.36; P = 0.87). There were no significant differences in PFS within any molecular subgroup. In substudy-2, 183 patients were randomized, 121 received durvalumab and 62 standard-of-care. Median PFS was 3.0 months (2.3-4.4) with durvalumab versus 3.0 months (2.0-5.1) with standard-of-care (HR, 0.86; 95% CI, 0.62-1.20; P = 0.38). Preplanned subgroup analysis showed an enhanced benefit with durvalumab in patients with PD-L1 tumor proportion score (TPS) ≥1%, (n = 29; HR, 0.29; 95% CI, 0.11-0.75) as compared with PD-L1 <1% (n = 31; HR, 0.71; 95% CI, 0.31-1.60; Pinteraction = 0.036).
Conclusions:
Molecular profiling can feasibly be implemented to guide treatment choice for the maintenance strategy in EGFR/ALK wt NSCLC; in this study it did not lead to substantial treatment benefits beyond durvalumab for PD-L1 ≥ 1 patients.
Insights
Targeted therapies and immune checkpoint blockers showed no significant benefit as maintenance therapy for advanced non-small cell lung cancer (NSCLC) patients. Durvalumab demonstrated a survival benefit only in patients with high PD-L1 expression.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Targeted therapies (TT) and immune checkpoint blockers (ICB) have transformed non-small cell lung cancer (NSCLC) treatment.
- The role of these therapies as maintenance treatment based on molecular profiling remains unclear.
Purpose of the Study:
- To evaluate the efficacy of TT and ICB as maintenance therapy in advanced EGFR, ALK wild-type (wt) NSCLC.
- To assess the impact of molecular characterization on treatment selection for maintenance strategies.
Main Methods:
- A randomized phase II trial (SAFIR02-Lung/IFCT 1301) involving 33 centers.
- Patients with advanced EGFR/ALK wt NSCLC, without progression after first-line chemotherapy, were randomized to receive either TT (substudy-1) or ICB (substudy-2) versus standard-of-care.
- High-throughput genome analysis was used for molecular characterization.
Main Results:
- In substudy-1, median progression-free survival (PFS) was 2.7 months for TT and 2.7 months for standard-of-care (HR, 0.97; P = 0.87).
- In substudy-2, median PFS was 3.0 months for durvalumab and 3.0 months for standard-of-care (HR, 0.86; P = 0.38).
- Durvalumab showed improved PFS in patients with PD-L1 tumor proportion score (TPS) ≥1% (HR, 0.29) compared to PD-L1 <1% (HR, 0.71; Pinteraction = 0.036).
Conclusions:
- Molecular profiling is feasible for guiding maintenance therapy in EGFR/ALK wt NSCLC.
- The study did not demonstrate substantial treatment benefits with TT or ICB as maintenance therapy, except for durvalumab in patients with PD-L1 TPS ≥1%.
