Abstract 1986P
Background
Immunotherapy either alone or in combination with chemotherapy has largely become the standard of care for patients with metastatic non-small cell lung cancer. In a small subset of patients, immune checkpoint inhibitors paradoxically can increase tumor growth and worsen overall survival, a phenomenon referred to as hyperprogression. Previous research has examined the role of MDM2 amplification as a predictor for hyperprogression across multiple different tumor types. Through its interaction and inhibition of p53, MDM2 amplification can lead to increased tumorigenesis. We sought to determine whether MDM2 amplification played a role in a cohort of NSCLCa patients who met clinical and or radiological criteria for hyperprogression.
Methods
Patients were selected based on previously reported radiological criteria; time to treatment failure <2 months, >50% increase in tumor burden compared with pre-immunotherapy imaging, acceleration of tumor growth kinetics (TGK ratio >2). MDM2 amplification was determined via fluorescent in-situ hybridization (FISH). Due to the close relationship between MDM2 and p53, immunohistochemistry (IHC) staining for p53 was carried out as a confirmatory assay.
Results
16 patients were identified as meeting previously defined criteria for hyperprogression. 9 had adenocarcinoma and 7 had squamous cell carcinoma. PDL-1 was expression was >1% in 13 patients and <1% in 3 patients. No targetable mutations were identified. 14 of the patients had a smoking history. 11 patients had tissue samples suitable for testing. No MDM2 amplification was seen with FISH in any of the 11 patients and in 10 of the 11 patients p53 staining was positive with IHC.
Conclusions
MDM2 amplification was not observed in any of the 11 identified patients who met criteria for hyperprogression contrary to previous reports outside of a lung cancer cohort. MDM2 has been reported as a negative regulator of p53 and given that p53 however remained positive on IHC in this study suggests that MDM2 here has not suppressed the p53 tumor suppressor gene. More research is needed to further clarify the role of MDM2 and its interaction with p53 in lung cancer patients who display hyperprogression post immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.