Abstract 862MO
Background
Despite the introduction of immune checkpoint inhibitors (ICI) in the management of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC), only a small subset of patients achieves long-term survivorship. In order to identify predictors of outcome, we evaluated gene expression profiles in patients at opposite ends of the spectrum of overall survival (OS) after ICI therapy.
Methods
In this retrospective, multicenter study, we analyzed gene expression (Clariom D, Affymetrix, Thermofisher) from histological samples of platinum-resistant RM-HNSCC patients treated with ICI alone. Each long-term survivor (LTS), defined as OS >18 months since the start of ICI, was matched with at least one short-term survivor (STS), defined as OS <6 months, according to site of recurrence (distant metastases only, or locoregional recurrence with/out metastases). We applied the Prediction Analysis for Microarrays classifier to infer six molecular HNSCC subtyping clusters, including immune related subtypes (De Cecco, Oncotarget 2015). Subsequently, a score was determined between each sample and the centroids for “Cl6-Immunereactive”.
Results
We analyzed a total of 26 LTS and 38 STS (clinical characteristics shown in table). We applied our six-subtype stratification to determine the samples belonging to the immune related clusters. In detail, LTS showed a positive association with Cl6 subtype score, while STS showed a negative association (p-value= 3.97E-06). The accuracy was investigated in terms of ROC analysis, reaching the significance with AUC = 81.3%; 95% CI: 71%-91.6% (DeLong-test). Table: 862MO
| Long-term survivors (26 pts) | Short-term survivors (38 pts) | |
| Gender Male | 21 (81%) | 32 (84%) |
| Age (years) Median (range) | 65 (19-78) | 59.5 (28-77) |
| Smoking (pack/year) Median (range) | 30 (0-80) | 30 (0-80) |
| Primary site of disease Oral cavity, Oropharynx, Hypopharynx, Larynx, Other | 7 (27%), 10 (38.5%), 1 (4%), 5 (19%) ,3 (11.5%) | 13 (34%), 9 (24%), 5 (13%), 11 (29%), 0 |
| ECOG Performance Status 0, 1 | 16 (61.5%), 10 (38.5%) | 12 (32%), 26 (68%) |
| Stage at ICI treatment DM only, LRR +/- DM | 7 (27%), 19 (73%) | 7 (18%), 31 (82%) |
| Line of ICI treatment First line, Second line | 20 (77%), 6 (23%) | 26 (68%), 12 (32%) |
| ICI Nivolumab Pembrolizumab | 21 (81%), 5 (19%) | 38 (100%), 0 |
| PFS (months) Median (range) | 16 (2-60+) | 2 (0-6) |
| OS (months) Median (range) | 21 (18-60+) | 3 (1-6) |
Conclusions
These preliminary data indicate the presence of underlying differences in gene expression profiles between LTS and STS after treatment with ICI for platinum-refractory RM-HNSCC. These observations need further study and may have translational implications improving treatment selection.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
AIRC (Associazione Italiana Ricerca sul Cancro) - IG 21740.
Disclosure
All authors have declared no conflicts of interest.
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