Journal of Immunotherapy and Precision Oncology (Jan 2023)

Predictors of Oncologic Outcome in Patients Receiving Phase I Investigational Therapy for Recurrent or Metastatic Cervical Cancer

  • Ji Son,
  • Heather Y. Lin,
  • Siqing Fu,
  • Amadeo B. Biter,
  • Ecaterina E. Dumbrava,
  • Daniel D. Karp,
  • Aung Naing,
  • Shubham Pant,
  • Sarina A. Piha-Paul,
  • Jordi Rodon,
  • Vivek Subbiah,
  • Apostolia M. Tsimberidou,
  • Timothy A. Yap,
  • Michael M. Frumovitz,
  • Amir A. Jazaeri,
  • Pedro T. Ramirez,
  • Shannon N. Westin,
  • Ying Yuan,
  • Funda Meric-Bernstam,
  • David S. Hong

DOI
https://doi.org/10.36401/JIPO-22-23

Abstract

Read online

Introduction: We aimed to identify clinical, pathologic, and treatment factors that are predictive of response and survival in patients with cervical cancer referred to phase I clinical trials. Methods: Patients with cervical cancer who received at least one dose of a phase I investigational agent at our institution between 2014 and 2022 were included. The log-rank test was used to analyze differences in progression-free survival (PFS) and overall survival (OS), and multivariable regression analysis was performed. Results: We included 65 patients with a median age of 41 years (range, 20–74), 3 prior therapies (range, 1–7), and 67.7% squamous carcinoma. The rate of distant metastasis at trial entry was 84.6%. The most common molecular alterations included PIK3CA (46.5%), PD-L1+ (46.2%), EPH (30.0%), and CREBBP (23.1%); 23.1% had received a prior checkpoint inhibitor. Phase I trials were for immunotherapy (58.5%) or targeted therapy (41.5%). The rate of biomarker matching was 21.5%. For all patients, median PFS was 3.6 months (95% CI, 2.0–5.2) and OS was 9.3 months (95% CI, 7.0–10.6). Factors at study entry associated with worse survival were presence of bone metastasis (PFS 1.6 vs 4.4 months: hazard ratio [HR], 2.8; p = 0.001; OS 3.8 vs 10.0 months: HR, 3.9; p < 0.0001) and absolute lymphocyte count below 1000/μL (PFS 1.8 vs 5.2 months: HR, 2.9; p = 0.0004; OS 7.0 vs 10.6 months: HR, 3.2; p = 0.0009). Factors associated only with worse OS were absolute neutrophil count above 4700/μL, hemoglobin below 10.5 g/dL, and smoking status. Grade 3+ treatment-related adverse events were seen in 16.9% of cases. Conclusion: Bone metastasis and absolute lymphocyte count below normal range at phase I study entry portend poor survival in patients with recurrent or metastatic cervical cancer.

Keywords