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.
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.
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