Introduction/Background Treatment options for patients with recurrent cervical cancer remain relatively limited. Human epidermal growth factor receptor 2 (HER2) targeting agent, such as Trastuzumab Deruxtecan (T-DXd) have shown promising efficacy with 75% overall response rate in HER2 3+ patients. In this study, we evaluated the histologic subtypes and immune markers of HER2-amplified cervical cancer.

Methodology We conducted a comprehensive review of electronic medical records for 130 patients diagnosed with advanced or recurrent cervical cancers, evaluating HER2 immunohistochemistry staining (IHC). The expression of HER2 was validated by dedicated pathologists at the center according to gastric cancer scoring in the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and categorized as 0, 1+, 2+, or 3 +. Additionally, the PD-L1 IHC 22C3 PharmDx Combined Positive Score (CPS) was assessed.

Results Among 69 patients with squamous cell carcinoma, only 7.2% showed HER2 IHC 2+ or 3%, while 35.3% of 34 adenocarcinoma cases and 37.0% of the 27 cases with other histologic types, such as neuroendocrine and adenosquamous carcinoma, exhibited elevated levels of HER2 (p-value 0.0005). Among patients expressing 2+ or 3+ HER2 and treated with the HER2-targeting agent, those treated with T-DXd displayed prolonged progression-free survival (PFS) after treatment, with a median of 17.5 months (n=4). Conversely, two patients treated with Trastuzumab emtansine (T-DM1) experienced a poor prognosis, with a median PFS of one month. In terms of PD-L1 expression with HER2, 20% with CPS 0 and 19.3% with CPS ≥1 expressed 2+ or 3+ of HER2 without significance (p-value=1).

Conclusion Our findings suggest that a specific subset of patients with cervical cancer displayed elevated levels of HER2 expression. These subtypes are known to be associated with a poor prognosis with conventional therapy, making them potentially suitable targets for high-efficacy treatments. Further studies are required to confirm the efficacy in HER2-amplified cervical cancer.

Disclosures Consulting/advisory board to AstraZeneca, CanariaBio, Eisai, Genmab, GI Innovation, ImmunoGen, MSD, and Seagen

Funded research from Advenchen, Ascendis Pharma, Alkermes, AstraZeneca, BeiGene, BerGenBio, BMS, CanariaBio, Cellid, Clovis Oncology, Eisai, Genmab, GII, GSK, ImmunoGen, Janssen, Merck, Mersana, MSD, Novartis, ONO, Regeneron, Roche, Seagen, Sutro, Synthon, and Takeda