N Engl J Med 2019 Dec 19
Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer.
Related Questions
Does the presence of an ATM mutation in advanced stage ovarian cancer influence the decision to use Bev vs PARP inhibitor for maintenance?
I would not use the presence of an ATM mutation alone to inform decisions between bevacizumab vs PARPi maintenance. There are several options for maintenance in the 1L setting, and these include single agent PARPi, PARPi + bevacizumab, or bevacizumab monotherapy. Using data from the PAOLA-1 trial, i...
Would you add a PARP inhibitor to bevacizumab maintenance for a patient with a high grade serous ovarian cancer with a germline BRCA2 variant of unknown significance and negative somatic testing?
The information above is insufficient in informing a treatment recommendation. As defined, the implications of the BRCA2 VUS are unclear. In this setting, I would advocate that HRD testing be performed on the tumor tissue. If the tumor is HRD+, I would certainly counsel the patient on the utility of...
When would you continue bevacizumab versus using PARPi alone for maintenance therapy in BRCA+ or HRD+ ovarian cancer after response to primary platinum + bevacizumab?
In patients who start treatment with combination platinum based chemotherapy + bevacizumab, and are found to be BRCA+ or HRD+, I will commonly continue bevacizumab and layer on the PARPi in the maintenance setting. This is based on both the PAOLA-1 data, as well as the population adjusted indirect c...
Is there any role for PARPi maintenance in BRCA-/HRD- patients after response to front line chemotherapy +/- bevacizumab?
This is a more complex question, and relies on a conversation with the patient and shared decision making. Unfortunately, the benefit seen with PARPi maintenance in BRCA-/HRD- patients was limited (PRIMA 8.1 vs. 5.4 months; PAOLA-1 16.9 vs. 16 months). I am also sensitive to implications of incorpor...
What factors impact your decision to include bevacizumab with primary chemotherapy for patients with BRCA+ or HRD+ ovarian cancer?
The decision for bev isn’t based on HRD or BRCA biomarkers – it is based on clinical factors and provider preference. Bev is approved for all epithelial ovarian cancer, advanced stage with and to follow platinum based chemotherapy based on a clinically and statistically significant improvement in PF...
What is your current practice for obtaining mutation status for a patient with newly diagnosed ovarian cancer?
My current practice is to test all newly diagnosed epithelial ovarian cancer patients (includes fallopian tube and peritoneal) with both germline multigene and somatic multigene/NGS panels. Only recently have I adopted the practice of concurrent testing at diagnosis rather than basing the decision t...
How are you counseling HR-proficient ovarian cancer patients about front line PARP inhibitor maintenance?
I think this is a tough decision, but I recommend observation for patients with HR proficient disease. In brief, I don't find a PFS advantage, without a proven OS advantage, enough to justify this long-term, expensive, and not non-toxic treatment.For BRCA carriers the answer is easier—with SOLO2 (20...
Would you recommend PARP inhibitor maintenance for a BRCA wild-type, HRD+ advanced ovarian cancer?
We have a better understanding of ovarian cancer biology now, including the importance of germline and somatic BRCA mutations, as well as the role of homologous recombination deficiency (HRD) in tumors and the potential benefit of new therapies in the maintenance.Considerations for maintenance thera...