Clinical and molecular signature of survival and resistance to olaparib plus pegylated liposomal doxorubicin in platinum-resistant ovarian cancer: a stratified analysis from the phase II clinical trial ROLANDO, GEICO-1601.

Objective: To determine the potential prognostic value of clinical and molecular biomarkers in the survival of patients with platinum-resistant ovarian cancer treated with olaparib and pegylated liposomal doxorubicin.
Methods: ROLANDO was a single-arm phase II trial that included patients with high-grade serous or endometrioid tumors and at least one previous platinum-resistant recurrence regardless of BRCA status. Patients received 6 cycles of pegylated liposomal doxorubicin every 28 days plus olaparib 300 mg twice daily. followed by olaparib 300 mg twice daily; monotherapy until progression or unacceptable toxicity. Prognostic factors including previous lines (and platinum-containing ones), BRCA mutation status, previous bevacizumab, CA-125 levels, and the neutrophil/lymphocyte ratio, lymphocyte/monocyte ratio, and platelet/lymphocyte ratio calculated at inclusion were analyzed through a multivariate logistic regression and factor analysis of mixed data.
Results: Thirty-one patients were included. Median age was 57 years (range 43-75), Eastern Cooperative Oncolgy Group performance status 0/1: 32.3%/67.7% and BRCA mutated: 16.1%. Prior treatment lines were >2 lines: 14 (45.2%) patients, ≥2 platinum lines: 21 patients (67.7%) and previous bevacizumab 19 (61.3%) patients. CA-125 was >2 upper limit normal in 24 (77.4%) patients. A high neutrophil/lymphocyte ratio was associated with worse overall survival by univariate/multivariate regression model (HR=11.18; 95% CI 1.1 to 114.5; p=0.042). No other factors were associated with overall survival in the multivariate model. A multifactorial signature based on clinical and molecular baseline characteristics was capable of defining six patient clusters. Three of these clusters had significantly better prognosis, with a median overall survival of 21.3 months (95% CI 12.2 to not reached).
Conclusions: High neutrophil/lymphocyte ratio at platinum-resistant relapse indicated poor prognosis in patients treated with olaparib plus pegylated liposomal doxorubicin. A multifactorial clinical signature was more precise than single variables for implying the prognosis and may help in therapeutic assignment after further validation in large prospective cohorts.
Competing Interests: Competing interests: MJR has served on advisory boards for MSD, AstraZeneca, Roche, GSK, Clovis, PharmaMar, and received support for travel or accommodation from Roche, AstraZeneca, MSD and PharmaMar. YGG declares participating in advisory boards from GSK, AstraZeneca, and Pharmamar, and declares fees from travel grants and speaker’s bureau from Roche, AstraZeneca, Pharmamar, MSD, GSK. ASB declares participating in advisory boards for MSD, AstraZeneca, GSK, Clovis, PharmaMar, and declares receiving support for travel from MSD and GSK, and speaker's bureau from MSD, AstraZeneca, GSK, Clovis. PE-G has served on advisory boards for MSD, AstraZeneca, GSK, Clovis, PharmaMar, and received support for travel or accommodation from GSK, AstraZeneca, MSD, and PharmaMar. All the other authors declare no conflicts of interest.
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