Association of Multiple High-Risk Factors on Observed Outcomes in Real-World Patients With Advanced Ovarian Cancer Treated With First-Line Therapy

Abstract

Purpose: To identify risk factors for disease progression or death and assess outcomes by risk categories in real-world patients with advanced ovarian cancer.

Methods: This retrospective study included adult patients from a nationwide electronic health record-derived deidentified database with stage III/IV ovarian cancer who received first-line therapy and had ≥12 weeks of follow-up after index date (end of first-line therapy). Factors predictive of time to next treatment and overall survival (OS) were assessed. Patients were grouped according to the cumulative number of high-risk factors present (stage IV disease, no debulking surgery or neoadjuvant therapy and interval debulking surgery, visible residual disease after surgery, and breast cancer gene [BRCA] wild-type disease/unknown BRCA status), and time to next treatment and OS were assessed.

Results: Region of residence, disease stage, histology, BRCA status, surgery modality, and visible residual disease were significant predictors of time to next treatment; age, Eastern Cooperative Oncology Group performance status, disease stage, BRCA status, surgery modality, visible residual disease, and platelet levels were significant predictors of OS (N = 1,920). Overall, 96.4%, 74.1%, and 40.3% of patients had at least 1, 2, or 3 high-risk factors, respectively; 15.7% of patients had all four high-risk factors. Observed median time to next treatment was 26.4 months (95% CI, 17.1 to 49.2) in patients with no high-risk factors and 4.6 months (95% CI, 4.1 to 5.7) in patients with four high-risk factors. Observed median OS was shorter among patients with more high-risk factors.

Conclusion: These results underscore the complexity of risk assessment and demonstrate the importance of assessing a patient's cumulative risk profile rather than the impact of individual high-risk factors. They also highlight the potential for bias in cross-trial comparisons of median progression-free survival because of differences in risk-factor distribution among patient populations.

FIG 1.

Patient attrition chart for the selection of patients with advanced ovarian cancer who received first-line therapy. ^aPatients who underwent debulking surgery and were missing either the surgical date or postoperative residual disease status were excluded. ^bPatients with incomplete medical history within 90 days of diagnosis or debulking surgery (no visit or noncanceled medication order within 90 days of diagnosis or debulking surgery) were excluded. PARP, poly(ADP-ribose) polymerase.

FIG 2.

Kaplan-Meier estimated (A) time to next treatment and (B) OS in patients who received first-line therapy (N = 1,920). OS, overall survival.

FIG 3.

Characteristics predictive of disease progression assessed by (A) time to next treatment and (B) OS in patients who received first-line therapy. HRs and 90% CIs assessed the impact of index characteristics on time to next treatment or OS. Values were calculated using a Cox proportional hazards model. ^aBorderline, clear cell, endometroid, mucinous, or transitional cell histologies. ^bPatients who did not undergo debulking surgery were assumed to have visible residual disease. BRCA, breast cancer gene; ECOG, Eastern Cooperative Oncology Group; HR, hazard ratio; OS, overall survival.

FIG 4.

Risk factor classification and distribution. (A) The percentage of patients by cumulative number of high-risk factors present. (B) The percentage of patients with each high-risk factor by the cumulative number of high-risk factors. ^aPatients who did not undergo debulking surgery were assumed to have visible residual disease. BRCA, breast cancer gene.

FIG 5.

Kaplan-Meier estimated (A) time to next treatment and (B) OS by the cumulative number of high-risk factors present at index in patients who received first-line therapy (N = 1,920). OS, overall survival.