Abstract 3682
Background
Neoadjuvant chemotherapy (CT) and immunotherapy (IT) are associated with features of pathologic treatment response (PTR) in NSCLC. Comparison of such features in NSCLC following neoadjuvant CT, IT or upfront surgical resection is lacking. Nivolumab (N) and/or N plus ipilumumab (NI) are being investigated in resectable NSCLC (NCT03158129). We analyzed the histopathologic patterns of CT- and IT-treated NSCLC vs untreated surgically resected tumors.
Methods
Histopathologic assessment of untreated, CT- and IT-treated NSCLC was performed (n = 30, 10/group). Hematoxylin and eosin-stained tumor sections were scored for parameters of PTR: percentage of viable tumor, fibrosis, and necrosis; inflammation, tertiary lymphoid structures (TLS), macrophages, lymphovascular invasion (LVI), cholesterol clefts (CC), giant cells (GC) and neovascularization (NV) were reported as a score (0-3). Values for each variable were expressed as a mean (± SD). Statistical comparison between two groups was calculated with unpaired two-sided t-test. Significance was defined as p-value <0.05.
Results
CT and IT were associated with significantly less viable tumor cells (p = 0.04 and p = 0.02, respectively), IT with more fibrosis (p = 0.04) and CT with more CC (p = 0.03) than untreated tumors. Trends towards higher amounts of inflammation, macrophages and CC were seen in IT-treated compared to untreated tumors. CT had a trend towards more fibrosis and GC compared with untreated NSCLC (Table).Table: 1928P
Summary of PTR parameters
| Untreated | CT-treated | IT-treated | |
|---|---|---|---|
| Viable tumor | 67.7% | 42.4%* | 37.5%* |
| Fibrosis | 26.6% | 46.6% | 52.3%* |
| Necrosis | 5.6% | 11.0% | 10.1% |
| Inflammation | 1.46 | 1.54 | 1.87 |
| TLS | 0.80 | 1.00 | 1.00 |
| LVI | 0.23 | 0.16 | 0.33 |
| Macrophages | 0.12 | 0.94 | 1.17 |
| CC | 0.13 | 0.92* | 1.04 |
| GC | 0.40 | 0.80 | 0.70 |
| NV | 0 | 0 | 0 |
p-value <0.05
Conclusions
Neoadjuvant CT and IT are associated with similar histopathological changes compared to untreated tumors but with lower proportions of viable tumor and higher degrees of fibrosis. Neoadjuvant treatment is also associated with a trend towards higher amounts of inflammation, macrophages, CC and GC. Analysis of a larger cohort, including comparison of N- vs NI-treated tumors (estimated n = 80) is ongoing and will be presented in due course.
Clinical trial identification
NCT03158129.
Legal entity responsible for the study
University of Texas MD Anderson Cancer Center.
Funding
The University of Texas MD Anderson Lung Cancer Moon Shot Program, Bristol-Myers Squibb.
Editorial Acknowledgement
Disclosure
B. Glisson: Research funding to institution: Medimmune, Pfizer, ISA Pharmaceuticals, Abbvie. G. Blumenschein: Consulting/advisory role: Bristol-Myers Squibb, Bayer, Clovis, Merck, Celgene, AbbVie, ARIAD; Research funding: Bristol-Myers Squibb, Novartis, Xcovery, AstraZeneca, Adaptimmune, Immatics, Macrogenetics, Bayer, Merck, Celegene, Genentech, GlaxoSmithKline, Kite Pharma; Travel, accomodations, expenses: BMS, AbbVie, Merck. J.V. Heymach: Advisory board: Bristol-Myers Squibb; Research/Grant: Bristol-Myers Squibb. All other authors have declared no conflicts of interest.
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