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Abstract
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.
- Ovary
Data availability statement
Data are available upon reasonable request. Already compiled analyzed data will be publicly available in clinicaltrials.gov and EudraCT platforms. Individual data may be provided upon request and sponsor authorisation. No identifiable data can be provided and the data can only be used for the same purposes as those of the curent research to comply with, and guarantee, patient data protection rights.
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Data availability statement
Data are available upon reasonable request. Already compiled analyzed data will be publicly available in clinicaltrials.gov and EudraCT platforms. Individual data may be provided upon request and sponsor authorisation. No identifiable data can be provided and the data can only be used for the same purposes as those of the curent research to comply with, and guarantee, patient data protection rights.
Footnotes
Contributors AP-F coordinator, planning, study design, methods, formal analysis, and original draft writing. AP-F acts as guarantor for this study. All authors contributed to conduct of the trial, manuscript writing, and revision.
Funding This work was supported by Grupo Español de Investigación en Cáncer de Ovario (GEICO). This research has had the financial collaboration of Astrazeneca Farmaceutica Spain S.A. but the collaborator did not take part in the conduct of the current clinical trial or in the analysis and interpretation of the results. Pegylated ribosomal doxorubicin was provided by the sites according to local standard procedures.
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.
Provenance and peer review Not commissioned; externally peer reviewed.
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