Eric Pujade-Lauraine, MD, PhD

Eric Pujade-Lauraine, MD, PhD, head of the Medical Oncology Department at Hôpital Hôtel-Dieu in France, discusses the prognostic factors researchers are looking for when testing patients with ovarian cancer.

According to Pujade-Lauraine, PARP inhibitors can be an effective treatment for patients with ovarian cancer and homologous recombination deficiency (HRD). Results from the phase 3 PAOLA-1 trial (NCT02477644) examining olaparib (Lynparza) added to bevacizumab (Avastin) in adult patients with ovarian cancer in complete or partial response to first-line platinum-based chemotherapy and whose cancer is associated with HRD, led to the approval of olaparib in this patient population.

Within this trial, patients were tested for tumor HRD status using the Myriad myChoice HRD Plus assay, and showed that patients with HRD positivity, regardless of 

 mutation status, benefited from the combination of olaparib and bevacizumab.

 We look for other prognostic factors. One important prognostic factor is the FICO stage, particularly in this advanced stage, the difference between stage 4 and stage 3 disease. Of course, it's more difficult to get a complete resection of all the sites of disease when it is a stage 4.

 The second most important prognostic factor is the possibility to achieve a complete resection at the upfront surgery. There are different methods to assess this basic capability of the disease when the disease is newly diagnosed. If it is considered, then it will be very difficult to get a complete surgical resection while we propose to the patient a cycle of a chemotherapy and interval debulking surgery, followed by chemotherapy, and then maintenance with a PARP inhibitor. At any point, you have to choose whether or not to add bevacizumab.

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Eric Pujade-Lauraine, MD, PhD, discusses the prognostic factors researchers are looking for when testing patients with ovarian cancer.

Prognostic Factors to Watch Out for in Patients With Ovarian Cancer

Eric Pujade-Lauraine, MD, PhD, head of the Medical Oncology Department at Hôpital Hôtel-Dieu in France, discusses the differences regarding testing for homologous recombination repair deficiency (HRD) in patients with ovarian cancer in France compared with other countries.

PARP inhibitors, including olaparib (Lynparza), niraparib (Zejula), and rucaparib (Rubraca), are an effective treatment option for patients with ovarian cancer. Based on findings from the phase 3 PAOLA-1 trial (NCT02477644), the combination of olaparib and and bevacizumab (Avastin) as a first-line maintenance therapy in adult patients with ovarian cancer was approved by the FDA and European Medicines Agency.

This trial sought to discover whether patients received any benefit from this combination regardless of 

 mutation status. Participants were tested for tumor HRD status using the Myriad myChoice CDx test and demonstrated patients with HRD positivity to benefit most from the regimen, regardless of 

Additionally, HRD testing with gene panels is another approach which works to identify patients with high-grade ovarian cancer who have mutations in homologous recombination repair pathway genes than the Myriad test.

 The process is quite different according to countries, of course. In Europe, we have the Myriad test available for only a few months. In France, what we propose is at diagnosis of a high-grade ovarian cancer, to look for Myriad HRD test. In these tests, you have both the results of the 

 mutation in the tumor and the genomic instability score. With these tests, you can recognize those patients who are HRD positive and can benefit the most from a PARP inhibitor, and those who are HRD negative, who [may not] benefit from a PARP inhibitor.

 Then when you have the results of these tests, you can choose if you want to give bevacizumab or not, in addition to the perspective of offering the patient a PARP inhibitor. This is currently the way we are doing it in Europe and particularly in France, for all patients with high-grade ovarian cancer and advanced disease.

1. Ray-Coquard I, Pautier P, Pignata S, et al; PAOLA-1 Investigators. Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. 

. 2019;381:2416-2428. doi:10.1056/NEJMoa1911361

2. Pujade-Lauraine E. Homologous recombination repair mutation gene panels (excluding BRCA) are not predictive of maintenance olaparib plus bevacizumab efficacy in the first-line PAOLA-1/ENGOT-ov25 trial. Presented at: 2021 Society of Gynecologic Oncology Annual Meeting; March 19-25; Virtual.

Eric Pujade-Lauraine, MD, discusses the differences in testing for homologous recombination repair deficiency in patients with ovarian cancer throughout countries.

Differences in HRD Testing for Ovarian Cancer Worldwide

Eric Pujade-Lauraine, MD, PhD, a medical oncologist at Universit&eacute; Paris Descartes in France, discusses the exploratory findings from the phase III JAVELIN Ovarian 200 trial, which investigated the use of combination avelumab (Bavencio) plus pegylated liposomal doxorubicin in patients with platinum-resistant, refractory ovarian cancer.

This large trial enrolled 556 patients and demonstrated clinical activity with the combination regimen. However, the activity was modest with a hazard ratio of 0.78 for progression-free survival (PFS) in this unselected patient population, says Pujade-Lauraine. There was an increased response rate of 13% with the combination therapy versus 4%, but these are still small findings.

Although the primary endpoint was not met in the trial in the overall population, Pujade-Lauraine says exploratory analyses were conducted to find specific patient populations that could benefit more from the combination versus chemotherapy alone. One prespecified analysis showed that expression of PD-L1 could predict clinical activity; there were hazard ratios of 0.65 for PFS and 0.72 for overall survival compared with chemotherapy for PD-L1positive patients.

Patients who received chemotherapy, responded, then relapsed and became resistant to treatment seemed to have more of a benefit from the combination regimen, Pujade-Lauraine explains. Whereas, the subgroup of patients with primary resistance to chemotherapy did not experience a benefit from the addition of avelumab. However, these subgroup analyses were not preplanned, and so these data are still exploratory.

Eric Pujade-Lauraine, MD, PhD, discusses the exploratory findings from the phase III JAVELIN Ovarian 200 trial, which investigated the use of combination avelumab plus pegylated liposomal doxorubicin in patients with platinum-resistant, refractory ovarian cancer.

Eric Pujade-Lauraine, MD, PhD | Authors

Articles

Prognostic Factors to Watch Out for in Patients With Ovarian Cancer

Differences in HRD Testing for Ovarian Cancer Worldwide

Exploratory Analyses for JAVELIN Ovarian 200 Demonstrate Potential for Immunotherapy in Select Subgroups