2334P - Pathologic patterns following different neoadjuvant therapies in non-small cell lung cancer (NSCLC)

Background

Neoadjuvant chemotherapy (CT), immunotherapy (IT) and combination CT/IT are associated with pathologic treatment response (PTR) in NSCLC. Comparison of pathologic patterns following CT, IT or CT/IT and upfront surgical resection is lacking. Recently, neoadjuvant nivolumab (N), N+ipilumumab (NI), N+CT and NI+CT have been investigated in the NEOSTAR trial (NCT03158129). We analyzed and compared the pathologic patterns of CT, IT and CT/IT-treated NSCLC and untreated resected NSCLC (total n=139).

Methods

Pathologic assessment of resected NSCLC from the NEOSTAR cohort (n=79), a CT-treated group (n=30) and an untreated group (n=30) was performed. H&E-stained tumor sections were scored for parameters commonly associated with PTR: percentages of viable tumor (VT), fibrosis and necrosis and rate of major pathologic response (MPR, ≤10% VT); inflammation (INF), foamy macrophages (FM), lymphovascular invasion (LVI), cholesterol clefts (CC), giant cells (GC), non-necrotizing granulomas (NNG), and neovascularization (NV) were scored from 0-3. Values for each variable were expressed as a median, except MPR (%). Cohorts were compared with Chi-squared or Kruskal-Wallis test and post-hoc pairwise comparisons were performed. Significance was defined as a two-sided p-value <0.05.

Results

NI and NI+CT were associated with significantly less VT (p=0.001, <.001) and more fibrosis (p=0.002, 0.008) than untreated tumors. MPR rates were highest in NI and NI+CT. Necrosis was higher in the CT cohort, INF in N and NI, FM in CT and NI+CT, CC in CT, and NNG in NI and N+CT. Table: 2334P

Summary of scored parameters

Conclusions

Neoadjuvant NI and NI+CT regimens were associated with significantly less VT and more fibrosis than untreated tumors and achieved higher rates of MPR compared to CT. Collectively, neoadjuvant IT-based treatments produced higher amounts of INF, FM, and NNG, highlighting the potential impact of dual IT on pathological tumor regression and patterns of immune-mediated features.

Clinical trial identification

NCT03158129.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Bristol Myers Squibb.

Disclosure

All authors have declared no conflicts of interest.