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Experts Provide Algorithm for Use of Bevacizumab and PARP Inhibitors in Patients With Newly Diagnosed, Advanced Ovarian Cancer
Adding biological agents like bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors to first-line chemotherapy has improved the prognosis of ovarian carcinoma. To develop a potential algorithm for the use of these agents in patients with newly diagnosed advanced ovarian cancer, Angiolo Gadducci, MD, and Stefania Cosio, MD, Department of Clinical and Experimental Medicine, Division of Gynecology and Obstetrics, University of Pisa, Pisa, Italy, analyzed the results of randomized clinical trials and summarized their findings in a recent review (Anticancer Res. 2021; doi:41:4673-4685).
Based on their analysis, the experts formulated the following treatment algorithm: After the first cycle of paclitaxel plus carboplatin chemotherapy is initiated, results of BRCA testing on a tissue sample collected during primary debulking surgery should be analyzed before the second cycle of such chemotherapy is given.
For patients with mutated BRCA, 5 cycles of chemotherapy should be given, followed by olaparib maintenance therapy in patients whose cancer responds to olaparib. Niraparib therapy also may be used.
In contrast, for patients with wild-type BRCA, the treatment approach depends on whether the homologous-recombination deficiency (HRD) assay is available and the presence or absence of risk factors for adverse events related to bevacizumab therapy. These risk factors include uncontrolled hypertension, clinical significant cardiovascular disease, a non-healing wound, and thrombotic or hemorrhagic disorders such as stroke, transient ischemic attack, or sub-arachnoid hemorrhage. Indications of gastrointestinal obstruction, or recent history (within the last 6 mo) of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess, are also contraindications to bevacizumab therapy.
If the HRD test result is positive and no contraindications to bevacizumab therapy exist, bevacizumab can be added concurrently to chemotherapy then used sequentially, then olaparib can be added as maintenance therapy in patients whose cancer responds to this agent. These recommendations are based on the results of the PAOLA-1 study, in which olaparib plus bevacizumab was associated with a median absolute progression-free survival (PFS) benefit of nearly 1 year when compared with placebo plus bevacizumab (hazard ratio [HR]=0.43) in patients with a positive HRD test results and wild-type BRCA.
If the HRD test result is negative or not available and no contraindications to bevacizumab therapy exist, bevacizumab can be added concurrently to chemotherapy then used sequentially as maintenance therapy.
In contrast, if the HRD test result is negative or not available in patients with contraindications to bevacizumab therapy, continued chemotherapy is recommended, followed by niraparib maintenance therapy if the cancer responds to this agent. In particular, patients with stage III disease with visible residual disease after primary debulking surgery, with inoperable disease, or with stage IV disease may benefit from this approach, as may patients who received neoadjuvant chemotherapy. These recommendations are based on the results of the PRIMA trial, in which niraparib resulted in a median absolute increase in PFS of 5.6 months compared with placebo (HR=0.62) in the intention-to-treat population.
In addition, analysis of immune checkpoint inhibitor trials led the review authors to conclude that “avelumab and atezolizumab have limited impact on the clinical outcome of patients with newly diagnosed ovarian carcinoma.”
