24MO - TROP-2, TF and NECTIN4 as targets for ADC treatment in cervical cancer

Background

If detected early, most cervical cancers associate with good prognosis. However, survival rates drop significantly for late stage or recurrent disease, and treatment options are limited. Antibody drug conjugates (ADCs) represents a new group of cancer drugs providing promising response rates across multiple cancer types. However, only the ADC tisotumab vedotin (TV) is approved by the Food and Drug Administration (FDA) for use in cervical cancer. The aim of this study was to assess the expression of the ADC target proteins TROP2, Tissue factor (TF) and NECTIN4 by immunohistochemistry (IHC) in a population based cervical cancer cohort.

Methods

A prospectively collected cohort of 525 cervical cancer patients with extensive clinicopathological data including follow-up was investigated. Membrane expression of TROP2, TF, and NECTIN4 was assessed by IHC on tumor sections assembled on tissue microarrays (TMAs). TMAs were scored according to the HercepTest criteria applied for HER2 detection in breast cancer diagnostics.

Results

All ADC targets had tumor-specific membranous expression. TROP2, TF and NECTIN4 were highly expressed (i.e., HercepTest 3+), in 37%, 29% and 4% of the tumor, respectively. Furthermore, 68%, 48% and 12% of the tumors had high to medium (i.e., HercepTest ≥2+) TROP2, TF and NECTIN4 expression, respectively. High TROP2 expression associated with vascular space invasion (p=0.009) and squamous, adenosquamous and undifferentiated histology (p<0.001). High to medium TF expression associated with low histologic grade (p=0.042) and squamous and adenosquamous histology (p<0.001). High NECTIN4 expression associated with low histological grade (p=0.03) and squamous histology (p<0.001).

Conclusions

TROP2, TF and NECTIN4 are highly expressed in cervical cancer. Clinical trials evaluating the safety and efficacy of ADCs are highly relevant in cervical cancer.

Legal entity responsible for the study

University of Bergen.

Funding

The Norwegian Cancer Society, the Norwegian Research Council, Helse Vest and the University of Bergen.

Disclosure

M.K. Halle: Financial Interests, Personal, Advisory Role: MSD. All other authors have declared no conflicts of interest.