Treatment for Advanced and Recurrent Endometrial Cancer

At the 2022 Great Debates & Updates in Women’s Oncology virtual meeting, BJ Rimel, MD, Cedars-Sinai Medical Center, Los Angeles, California, shared best practices when treating patients with advanced and recurrent endometrial cancer.

In her presentation, Dr Rimel discussed important considerations to take when it comes to the potential for surgery, chemotherapy regimens, and options for maintenance therapy.

Transcript

Hi. My name is BJ Rimel. I'm a gynecologic oncologist at Cedars-Sinai Medical Center in Los Angeles. I'm going to talk briefly about upfront treatment in ovarian cancer, specifically a little bit about surgery, chemotherapy agents, maintenance therapy.

First, as everyone probably already knows, ovarian cancer continues to be a disease primarily diagnosed at late stages, and because of this, we are confronted with a situation, as gynecologic oncologists, of whether it is appropriate to treat a patient initially with surgery or with neoadjuvant chemotherapy. It continues to be our standard of care that, whenever possible and safe and appropriate for a patient, we want to engage in cytoreductive surgery with the goal being no visible residual disease to hopefully promote the best outcome for our patient. Obviously, this is not always possible, if a patient has significant comorbidities, or stage IV disease, or disease that is simply unresectable. When this happens, we can consider neoadjuvant chemotherapy, with several trials to support its use in this setting.

Primarily, we continue to use carboplatin and paclitaxel as our mainstay of drugs in the initial setting of treatment, either through neoadjuvant or adjuvant therapy. The addition of bevacizumab to these 2 drugs was considered in ICON7 and GOG-0218 and is still considered to be a reasonable option. It was also used in the PAOLA-1 study in combination with olaparib and was noted to be beneficial for patients with [homologous recombination deficiency] HRD-positive or BRCA-positive disease in the PAOLA-1 study.

That brings me to maintenance therapy. After the completion of 6 cycles of platinum-based doublet therapy, ideally carboplatin and paclitaxel for most patients, we are left with an opportunity to provide maintenance therapy. Patients should have already been BRCA tested; both germline and somatic testing is ideal. An assessment of an HRD-status is also recommended — this is because we can offer these patients maintenance therapy with a PARP inhibitor. If a patient has continued to have bevacizumab throughout their adjuvant or neoadjuvant treatment, they can be eligible for olaparib if they're HRD-positive or BRCA-positive, as I already mentioned, via the PAOLA-1 study.

If a patient has not had bevacizumab or does not wish to continue, olaparib can be considered for patients who are BRCA-positive, and the SOLO1 study gives us the most amazing results for these patients, with significant improvement in both progression-free and overall survival, which has been recently demonstrated at an overall survival analysis of 5 years, where the patients who were germline BRCA-positive demonstrated a significant improvement in progression-free and overall survival at 5 years. We’re excited, especially for this population.

For the HRD-positive population, we have several studies that demonstrate a significant effect, although the magnitude of benefit is somewhat diminished compared to those patients who are germline BRCA-positive. That magnitude of benefit though should still be considered and discussed with all patients, and we have the PRIMA study to give us this information. We now have ATHENA-MONO, which also demonstrated that homologous recombination deficient patients could continue to benefit as well as BRCA patients with rucaparib or niraparib.

These 2 studies continue to tell us that this medication is available, and the magnitude of benefit is quite significant, with greater than 9 months for many patients. However, for our HRD proficient patients or homologous recombination proficient patients, those who are not BRCA-positive and do not have a germline mutation and an HRD gene, nor have a score on any of the available tests that makes them homologous recombination deficient, we have the PRIMA study, and the PRIME study that both demonstrate an effect in this group. However, the magnitude of benefit is not as great as it is for the homologous recombination deficient patients and the BRCA-positive patients, and this should be discussed with the patient, as some people will not wish to take on both the risks of a PARP inhibitor or the side effect profile. The side effect profile of PARP inhibitors, as everyone probably knows, is primarily anemia, fatigue, and nausea, and this is throughout all the PARP inhibitors. Some have more specific other effects, such as thrombocytopenia with niraparib and changes in creatinine with rucaparib. These should be noted with your patient.

Thinking of other maintenance therapy, we always have bevacizumab, which was demonstrated in GOG-0218 and ICON7 to improve progression-free survival by about 3-plus months. This benefit is about the same as we see for homologous recombination proficient patients treated with PARP inhibitor. It should be noted that this does not necessarily overlap, and patients can choose one or the other.

From Los Angeles, thank you for listening, and have a great day.

Source

Rimel, B. Updates in Advanced and Recurrent Endometrial Cancer. Presented at: Great Debates & Updates in Women’s Oncology. Sep 21-23, 2022. Virtual.