|Ahead of print publication
Rucabarib: A new lease of life for ovarian cancer patients
Sandeep Sachdeva1, Tamkin Khan Rabbani2
1 Department of Community Medicine, SN Medical College, Agra, UP and Advisory Epidemiologist, Global Data Communications, London, United Kingdom
2 Department of Obstetrics and Gynaecology, JN Medical College, Aligarh Muslim University, Aligarh, Uttar Pradesh, India
|Date of Submission||28-Jun-2019|
|Date of Acceptance||01-Dec-2019|
|Date of Web Publication||27-Apr-2021|
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Source of Support: None, Conflict of Interest: None
Background: Rucaparib is a drug with potential as maintenence monotherapy in ovarian cancers irrespective of genetic mutation.
Methods: The results of the ARIEL 3 trial were analysed for the drug's prospects towards cure in ovarian and other pelvic malignancies.
Results: Ovarian cancer patients with highly malignant tumors and relapses on platinum based chemotherapy exhibited statistically significant reductions in tumor size with maintenance Rucaparib therapy vis a vis placebo.
Conclusion: Genetic heterogeneity of the tumor did not have an impact upon Rucaparib efficacy in ovarian carcinoma. More malignant and relapsed variants can effectively be treated with Rucaparib, thereby improving survival rates and quality of life.
Keywords: ARIEL 3 study, ovarian cancer, rucaparib
High-grade epithelial ovarian cancer, along with fallopian tube and primary peritoneal cancers are generally responsive (partially or completely) to platinum-based chemotherapy. Significant scientific evidence has proven rucaparib to be of substantial promise as monotherapy for the maintenance of ovarian cancer patients regardless of genetic mutation. The ARIEL 3 randomized controlled trial has shown a statistically significant reduction in the time required for third-line chemotherapy when maintenance therapy with rucaparib was instituted promptly in candidate patients. The clinical trial primarily assessed the efficacy of rucaparib vis-a-vis placebo following response to second-line chemotherapy in patients with highly virulent carcinoma, along with relapses of platinum-responsive ovarian carcinoma.
The ARIEL 3 trial: This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete.
The study design involves multicentric, randomized, double-blind, parallel, placebo-controlled, phase 3 intervention trial.
The duration of the study was from January 2014 to April 2017.
Adult females (above 18 years of age) with recurrent high-grade epithelial, fallopian tube or primary peritoneal cancer having undergone at least two prior platinum-based chemotherapies and attained complete or partial response to immediate prior platinum-based therapy with a CA 125 concentrations less than the upper limit of normal. Furthermore, recuparib must have been commenced within 8 weeks of the last chemotherapy dose as well to qualify for inclusion. The size of (any) residual tumor was not a constraint.
Patients who had received previous treatment with a poly (ADP-ribose) polymerase inhibitor (PARPi drugs) were excluded.
An Eastern Cooperative Oncology Group Performance score surpassing 1.
All comers (ITT population) including BRCA or/and homologous recombination deficiency (HRD+) mutations were strategically stratified to enable a step-down analysis in three prospectively defined nested cohorts.
A total of 564 patients were enrolled and parallel double-blinded randomization effected with 375 patients receiving rucaparib and placebo administered to 189 recruits. Randomization was effected in a 2:1 proportion to receive rucaparib or placebo. Stratification was by homologous recombination repair (HRR) status, next-generation sequencing mutation analysis, response (complete/partial) and progression-free response to the penultimate regimen to the recent platinum-based regimen on 6–12 months and beyond 12 months of follow-up period.
Primary outcome measure
Investigator-assessed progression-free survival (PFS) for three constituted nested cohorts for the trial, namely, patients with BRCA mutations, patients with HRD and the ITT (intention-to-treat) population.
Secondary outcome measure
PFS (by BICR) derived from the analysis of survival statistics.
Across all primary analysis groups, rucaparib significantly improved PFS in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL 3 provides further evidence that the use of a PARPi in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy.
The results of the AERIAL 3 trial derived from investigator based assessment revealed a statistically significant improvement (P < 0.025) in median PFS with the administration of rucaparib among all the three cohorts, regardless of gene mutation. A marked 64% reduction in the risk of disease progression or mortality was noted thereof. The null hypotheses proposed in the form of primary and secondary endpoints were statistically proven right.
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Conflicts of interest
There are no conflicts of interest.