At the 2024 Chinese Congress on Holistic Integrative Oncology (CCHIO), Dr. Xinping Cao from Sun Yat-sen University Cancer Center presented a comprehensive lecture titled “Advances in Systemic Therapy for Cervical Cancer.” Below is a summary of the key highlights.

1. Induction Therapy for Initial Cervical Cancer

Induction Chemotherapy

  • The INTERLACE trial demonstrated that short-term induction chemotherapy before standard chemoradiotherapy (CRT) significantly improved survival in locally advanced cervical cancer (LACC): 5-year OS: 80% vs. 72% (P = 0.04) 5-year PFS: 73% vs. 64% (P = 0.013).

Induction Chemotherapy Combined with Immunotherapy

  • NACI trial: A Phase II study showed promising results with neoadjuvant chemotherapy combined with camrelizumab: ORR: 98% (CR: 19%, pCR: 38%).
  • Sindilizumab + Paclitaxel + Cisplatin: Achieved 97.9% ORR in another Phase II study, with a pCR rate of 36.2%.

2. Concurrent Chemoradiotherapy (cCRT)

Chemotherapy with Radiation

  • Studies published in NEJM and other journals confirmed that weekly cisplatin (40 mg/m²) remains the gold-standard regimen for cCRT in LACC.
  • A randomized trial suggested that cisplatin (75 mg/m² every 3 weeks) could provide improved outcomes compared to weekly dosing.

Immunotherapy with Radiation

  • CALLA Trial: Durvalumab with cCRT did not improve PFS.
  • KEYNOTE-A18 Trial: Pembrolizumab combined with cCRT demonstrated significant improvements: 2-year PFS: 67.8% vs. 57.3% (HR = 0.70, P = 0.002).

3. Adjuvant Therapy After Definitive Radiation

OUTBACK Trial

  • Comparing CRT with and without adjuvant chemotherapy, the trial found no additional survival benefit from adjuvant chemotherapy: 5-year OS: 72% vs. 71%. 5-year PFS: 63% vs. 61%.

4. First-Line Therapy for Advanced Cervical Cancer

Preferred Regimens

The NCCN Guidelines (2024) recommend:

  • PD-L1-positive tumors: Pembrolizumab + platinum/paclitaxel ± bevacizumab (Category 1).
  • Other options: Platinum/paclitaxel/bevacizumab.

KEYNOTE-826 Trial

  • Pembrolizumab + chemotherapy ± bevacizumab significantly improved OS and PFS for persistent, recurrent, or metastatic cervical cancer: OS (PD-L1 CPS ≥ 10): 29.6 vs. 17.4 months. OS (PD-L1 CPS ≥ 1): 28.6 vs. 16.5 months.

COMPASSION-16 Trial

  • Cadonilimab (PD-1/CTLA-4 bispecific antibody) with platinum chemotherapy ± bevacizumab demonstrated superior results: OS (ITT population): Median OS not reached vs. 22.8 months. 12-month OS rate: 83.1% vs. 73.7%.

5. Second-Line Therapy for Recurrent/Metastatic Cervical Cancer

Immunotherapy

  • KEYNOTE-158 Trial: Pembrolizumab monotherapy for PD-L1-positive patients: ORR: 14.3%.
  • Nivolumab: Effective irrespective of PD-L1 expression, with an ORR of 25.3%.

Cadonilimab

  • ORR of 32.3% in patients with PD-L1-positive tumors (CPS ≥ 1): PD-L1-positive ORR: 42.9%. PD-L1-negative ORR: 16.7%.

Dual Antibodies (PD-1 + CTLA-4)

  • Combined therapies yielded ORR: 33.8%, with median PFS of 5.4 months.

Antibody-Drug Conjugate (ADC): Tisotumab Vedotin

  • InnovaTV 204 Study: Achieved ORR of 24% in second/third-line settings with a disease control rate of 72%.

Summary of Systemic Therapy for Cervical Cancer

Neoadjuvant Therapy

  • Pre-surgery pCR reached 33% in certain trials, showing promising early results.
  • Pre-radiation neoadjuvant therapy demonstrated both short-term and long-term efficacy.

Concurrent Chemoradiotherapy

  • Three-weekly cisplatin was shown to outperform weekly cisplatin regimens.

Adjuvant/Maintenance Therapy

  • No positive outcomes reported in current trials.

Advanced Disease

  • Significant extensions in median survival were observed in advanced cervical cancer patients, with long-term survival or potential curative outcomes through conversion to localized disease for some patients.

Cervical cancer treatment continues to evolve, with systemic therapies playing an increasingly pivotal role in improving outcomes. New approaches like immunotherapy, ADCs, and bispecific antibodies offer a brighter future for patients.

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Dr. Xinping Cao

  • MD, PhD, Chief Physician, and Clinical Principal Investigator
  • Chair, Brachytherapy Committee of the Chinese Anti-Cancer Association (CACA)
  • Vice Chair, Chinese Medical Association Radiation Oncology Committee
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Last updated on 2024.12.11