A new phase II umbrella trial has demonstrated promising results for anti-PD1 based precision induction therapy in patients with unresectable stage III non-small cell lung cancer (NSCLC), achieving significant pathological responses and identifying novel biomarkers for treatment stratification.
Study Design and Key Findings
The single-center trial enrolled 100 patients between January 2021 and March 2023, dividing them into chemo-free and chemotherapy subgroups based on PD-L1 expression levels. The study met its primary endpoint with a major pathological response (MPR) rate of 61.7% among patients who underwent surgery.
In the chemo-free subgroup, patients with PD-L1-positive expression received sintilimab (anti-PD1) combined with IBI305 (anti-VEGF biosimilar), achieving an MPR rate of 55.6% with notably lower treatment-related toxicity. The chemotherapy subgroup, comprising patients with negative or low PD-L1 expression, demonstrated an MPR rate of 63.2% when treated with immunotherapy plus chemotherapy.
Survival Outcomes and Safety Profile
The median follow-up period was 25.4 months, with 71% of participants surviving at data cutoff. The estimated 12-month overall survival rate was 83.5%, while the event-free survival rate was 78.5%. The chemo-free subgroup showed particularly encouraging results, with both one-year overall survival and event-free survival rates at 95%.
Treatment-related adverse events occurred in 90% of patients, with higher incidence in the chemotherapy subgroup (96.2%) compared to the chemo-free group (76.2%). Grade 3 or higher adverse events were observed in 35% of patients overall, affecting 40.5% of the chemotherapy group versus 14.3% of the chemo-free group.
Novel Biomarker Discovery
Through comprehensive genomic and transcriptomic analysis, researchers identified BST1 (Bone Marrow Stromal Cell Antigen 1) as a promising biomarker for immunotherapy response. High BST1 expression correlated with increased immune cell infiltration and better survival outcomes, potentially offering a new tool for patient stratification beyond PD-L1 status.
Clinical Implications
The study's findings suggest that precision-based induction therapy could provide an effective treatment strategy for unresectable stage III NSCLC patients. The identification of BST1 as a complementary biomarker to PD-L1 expression may enable more precise patient selection for combination immunotherapy approaches.
The surgical conversion rates were notable, with 42.9% in the chemo-free subgroup and 48.1% in the chemotherapy subgroup achieving successful surgical resection after induction therapy. All surgical procedures achieved R0 resection status, indicating complete tumor removal with clear margins.
Future Directions
While these results are promising, the researchers acknowledge the study's limitations, including its single-center design and relatively small sample size. Further validation through larger, randomized clinical trials across diverse patient populations will be necessary to confirm these findings and establish optimal treatment strategies based on molecular markers.
