ESMO Congress 2023 | OncologyPRO

Abstract 2334P

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

	Untreated (n=30)	CT (n=30)	N (n=21)	NI (n=16)	N+CT (n=22)	NI+CT (n=20)	p-value
VT	65.8%	48.5%	50%	9%	50.5%	4.5%	<.001
Fibrosis	26.3%	26.1%	40.5%	84%	45%	61.4%	<.001
Necrosis	0.31%	1.71%	1.5%	0%	0%	0%	0.029
MPR	-	17%	24%	50%	32%	55%	0.028
INF	1.37	1.29	2	1.66	1	1.09	0.007
FM	0	0.4	0	0.16	0	0.89	0.015
LVI	0.06	0.23	0	0	0.02	0	0.109
CC	0	0.86	0.4	0	0.13	0.47	<.001
GC	0	0.47	0.2	0.49	0.21	0.28	0.080
NNG (min, max)	0 (0, 0.25)	0 (0, 0)	0 (0, 1.1)	0 (0, 2.66)	0 (0, 2.25)	0 (0, 1.57)	0.004
NV	0	0	0	0.57	0.22	0.18	0.166

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.