Cervical Cancer Treatment and Prognosis: Revelations from ESMO 2024 Gynaecological Cancers Congress

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ONCOLOGY

Medical writer: Audrey TANG | Last updated: 16 September 2024 | In: Oncology

Article Keywords

human papillomavirus, prognosis, pembrolizumab, cervical cancer, chemoradiotherapy

Cervical cancer (CC) is the 4^th most common cancer in women worldwide, with approximately 660,000 new cases in 2022.¹ In Hong Kong, it was the 7^th most common cancer among women in 2021, with approximately 600 new cases and 178 deaths.² Here we report new findings on CC treatment and prognostic methods from three abstracts published at the annual ESMO Gynaecological Cancer Congress, 20–22 June 2024, Florence, Italy.

Efficacy and Safety of Chemoradiotherapy with or without Pembrolizumab in High-risk LACC Patients: Results for East-Asian Patients

The global, phase 3 KEYNOTE-A18/ENGOT-cx11/GOG-3047 trial (NCT04221945) demonstrated the efficacy of concurrent chemoradiotherapy (CCRT) with pembrolizumab (pembro) over placebo (PBO) in high-risk locally advanced CC (LACC) patients.³ In this study, efficacy of CCRT with or without pembro over PBO was examined among East-Asian patients enrolled in the trial. Newly diagnosed, treatment-naïve patients (n=299) with high-risk LACC (2014 International Federation of Gynecology and Obstetrics [FIGO 2014] stage IB2–IIB with node-positive disease or stage III–IVA regardless of lymph node status) were included.³ Patients were randomly assigned to pembro + CCRT (n=153) or PBO + CCRT (n=146) group.³ The primary endpoints were progression-free survival (PFS) and overall survival (OS).³ Median follow-up at database cutoff was 19.3 months.³ Results revealed that pembro + CCRT demonstrated an improvement over PBO + CCRT in PFS, with median PFS not reached in either treatment group (HR [Hazard Ratio]=0.55; 95% CI [Confidence Interval], 0.35–0.88); and a 24-month PFS rate of 77.6% vs 59.8%.³ Notably, rates of grade ≥3 treatment-related adverse events were similar in both groups (pembro + CCRT: 78.3%; PBO + CCRT: 77.4%); immune-mediated adverse events occurred more frequently with pembro + CCRT at 43.4%, compared to 10.3% with PBO + CCRT.³ Nonetheless, the results from the East Asia subgroup are consistent with the global analysis, where pembro + CCRT demonstrated PFS benefit vs PBO + CCRT with manageable safety.³ Pembro + CCRT may be considered as a new treatment option for patients with high-risk LACC in East Asia.³

PROs with Coformulated Vibostolimab/pembrolizumab for Locally Recurrent or Metastatic CC: Results from the KEYVIBE-005 Study

The multicohort, phase 2 KEYVIBE-005 study (NCT05007106) demonstrated that first-line vibostolimab (vibo)/pembro showed antitumour activity similar to pembro, with a manageable safety profile, among treatment-naïve locally recurrent or metastatic CC patients.⁴ This study presented prespecified patient-reported outcomes (PROs) endpoints of CC patients who received coformulated vibo/pembro or pembro alone.⁴ Patients (n=166) with untreated locally recurrent or metastatic CC with programmed death-ligand 1 combined positive score (PD-L1 CPS) ≥1 were randomly assigned 1:1 to vibo/pembro or pembro intravenously Q3W for ≤35 cycles.⁴ Prespecified PRO endpoints included least squares mean (LSM) change from baseline (BL) to week 12 in European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 global health status/quality of life (GHS/QoL) and physical functioning (PF) subscales, EORTC QLQ-CX24 symptom experience subscale, and EQ-5D-5L visual analogue scale (VAS) health status score.⁴ At week 12, completion and compliance rates in both groups were ≥64% and ≥86%, resepectively.⁴ The PRO assessments demonstrated that patients in both groups experienced small changes in EORTC QLQ-C30 GHS/QoL and PF, EORTC QLQ-CX24 symptom experience, and EQ-5D-5L scores, with overlapping CIs. None of the differences in LSM change from BL to week 12 between the two groups were clinically meaningful. For all PRO assessments, the change from BL to week 12 with vibo/pembro was similar to pembro alone, showing that vibo/pembro did not negatively impact health-related QoL in this patient population.

Prognostic Value of Circulating Tumour HPV DNA in CC

Persistent infection with high-risk human papillomavirus (HPV) is a known cause of CC.⁵ The prospective, observational clinical study NCT05602831 investigated the prognostic potential of circulating tumour HPV deoxyribonucleic acid (ctHPV-DNA) in monitoring treatment response and predicting recurrence in CC.⁵ Blood samples were collected for HPV digital droplet polymerase chain reaction testing, targeting the HPV16/18/33/52/58 to assess HPV clearance in relation to treatment efficacy.⁵ 43 patients were enrolled, with 27 completing sequential blood collections and 23 undergoing baseline tissue and ctHPV-DNA testing.⁵ Out of the 23 patients, all have squamous CC, with a mean age of 55 years and 82.6% (19/23) are at stage III.⁵ The concordance between baseline ctHPV-DNA and tissue HPV testing was 100%. Eighteen tissue-confirmed HPV-positive patients were analysed for the ctHPV-DNA dynamic surveillance including 13 HPV16-positive, 3 HPV58-positive, 1 HPV52-positive, and 1 HPV18-positive.⁵ There was a positive correlation between baseline tissue HPV copy number and ctHPV-DNA copy number (r=0.4718; p=0.0615). Patients with stage IIIC had higher ctHPV-DNA copy numbers than stage IIIB. Four post-radiation patients (22.22%) tested positive for ctHPV-DNA, with 2 experiencing relapse.⁵ Detailed case studies demonstrated that early detection of recurrence, 105 days ahead of imaging and 90 days ahead of tumour marker squamous cell carcinoma-antigen elevation, was possible using ctHPV-DNA, highlighting its prognostic value.⁵ The study demonstrated a strong correlation between ctHPV-DNA and tissue HPV testing, thus making ctHPV-DNA a valuable prognostic tool for CC.

References

World Health Organization. Available online. https://www.who.int/news-room/fact-sheets/detail/cervical-cancer. Last accessed: 5 September 2024.

Hong Kong Cancer Registry. Available online. https://www3.ha.org.hk/cancereg/. Last accessed: 5 September 2024.

Xiang Y, et al. ESMO Open. 2024;9(Supplement 5):103523.

Yonemori K, et al. ESMO Open. 2024;9(Supplement 5):103525.

Wen H, et al. ESMO Open. 2024;9(Supplement 5):103512.

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Disclaimer

This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).