Advanced ovarian cancer: what is the best treatment for initial diagnosis today?

With PARP inhibitors, the prognosis for ovarian cancer has improved significantly. How should a newly diagnosed high-grade malignancy be treated?

Frontline therapy offers best and often only chance of cure

Due to the continuous improvements in progression-free survival (PFS), a cure for ovarian cancer is now a realistic option, Prof. Herzog pointed out right from the start. It is important to make the best possible use of the narrow potential time window for recovery, especially post-operatively.

The renowned expert addressed if surgery (primary debulking) or neoadjuvant chemotherapy should be the first step in achieving maximum cytoreduction as follows, given current study data. To Prof. Herzog, a postponement of surgery should only be considered if an R0 resection is unlikely, or if there is a high comorbidity.

Options after standard chemotherapy

In the first line, surgical intervention is usually followed by combination therapy with carboplatin and paclitaxel before further options are offered in the therapeutic algorithm. On the basis of the latest studies, Prof. Herzog shows that dose-dense chemotherapy (DDC) and intraperitoneal chemotherapy (IP) have tended not to prove successful in advanced ovarian cancer, if only for reasons of toxicity.

The use of HIPEC, i.e. hyperthermic intraoperative intraperitoneal chemotherapy, can be considered, but according to the speaker it is only suitable for certain constellations and still has some question marks.

The administration of the bevacizumab antibody, in addition to chemotherapy, or as maintenance therapy, is optional for newly diagnosed ovarian cancer according to the current guidelines of the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO).

PARP inhibitors transform treatment - even beyond BRCA

The recommendations are clearer with regard to proven BRCA1/2 mutations, for which the guidelines favour the administration of poly-ADP-ribose polymerase (PARP) inhibitors regardless of antibody treatment. Specifically, the novel drug can achieve the most significant gains in absolute PFS benefit, especially in this biomarker-positive population. Due to the demonstrably large prognostic advantage, the PARP blocker should already be given as a frontline medication in this molecular subgroup - by no means should its use be saved for a possible second-line treatment, as Prof. Herzog emphasises.

But PARP inhibitors can also be used successfully for other genome damage caused by homologous recombination deficiency (HRD), which is why appropriate testing is definitely indicated. For HRD-negative tumours, which account for about half of all high-grade serous ovarian carcinomas (HGSOC), novel drug developments such as antibody-drug conjugates (ADCs), immunotherapies or vaccinations are used in addition to PARP inhibitors and bevacizumab.

Plenty in the pipeline

"Identifying unique drivers with inherent or inducible lethality is advancing tumour-specific therapies," the expert emphasised. In the last six years, there have been 14 new approvals in the USA alone. Especially in maintenance therapy, a new era has dawned with regard to advanced ovarian carcinoma, which primarily concerns the paradigm shift "PARPi, beyond BRCA too!"

Aspects that have not yet been answered are currently being investigated by a large number of exciting research projects, which focus in particular on the combination of PARP inhibitors with biologics as well as with immunotherapies. 

In conclusion, the oncologist appeals to patients to be treated in clinical trials, if possible. These remain the primary means of changing and improving treatment standards. Especially adaptive, leaner settings with larger deltas are necessary and desirable here.

Conclusion for medical practice

In advanced ovarian cancer, the prognosis is largely determined by the extent of tumour reduction at the first surgery. The backbone of chemotherapy is carboplatin and paclitaxel, followed by maintenance therapy with either bevacizumab, a PARP inhibitor or a combination of both. The choice is mainly determined by the presence of HRD and BRCA1/2 status. The current research successes in linking proven and innovative agents give hope that affected patients can benefit from a survival advantage that continues to grow steadily.


How to Treat Best Advanced Ovarian Cancer? Presidential Lecture by Prof. Thomas Herzog, University of Cincinnati Cancer Institute, 12th International Charité Mayo Conference, 29. April 2023