Assessing Therapeutic Approach to Treatment-Naïve Advanced Ovarian Cancer

In the past, when a woman presented with advanced ovarian cancer, the treatment approach wasn’t all that complicated, explained Kathleen Moore, MD, MS, during a presentation at the Society of Gynecologic Cancers 2022 Annual Meeting on Women’s Cancer. The standard approach was starting by operating on the patient and then administering paclitaxel and carboplatin.

“And that was about it, and then we went on with our day. There wasn’t a whole lot of thought that went into that,” Moore said. “But just in my relatively brief career, times have changed.”

Today, clinicians are working to meet women where they present and planning an individualized approach that account for the appropriate timing of surgery with clear definitions for surgical outcomes, considerations of comorbidities, as well as understanding how each patient’s pathologies may differ, Moore explained.

“When I was a fellow, when we enrolled [patients] in clinical trials, it was just epithelial ovarian cancer, and it didn’t matter what cell type, they all went on the same study,” Moore said. “In retrospect, that seems so naïve. We would never do that today because we understand that these are different diseases.”

Today, the genomic and molecular profile have become and will continue to be a key feature to understand when making decisions around patients’ treatment, Moore explained. Further, there are multiple therapies that are used today for sequencing, with new targeted agents in the pipeline, which allow many patients to have a markedly prolonged overall survival time.

However, this is accomplished by cobbling treatments together, Moore noted. This process requires patients to remain on a sequence of therapies for the remainder of their lives. Because of the problems that can result, Moore noted that it is important to continue to assess how treatment can be optimized for quality of life, potentially even allowing for patients to be cured in the front line.

Moore also noted that the current molecular landscape of advanced ovarian cancer has remained the same in recent years.

“When we think about BRCA mutation rates amongst that population, about 25% will have some sort of BRCA deleterious mutation, 18% are germline, and an additional 7% are somatic,” Moore said. “That really hasn’t changed, even when you look internationally, it’s pretty consistent.”

There are also additional mutations that are currently being tested for in patients outside of BRCA1/2, such as PALB2, BARD1, BRIP1, RAD51C, MSH2, MLH1, PMS2, and MSH6. All these mutations are being tested and assessed in prospective studies, the data from which allow for investigators to collect information to inform treatment for even rare subtypes. These data then provide clinicians with the opportunity to assess more clearly whether a result is predictive of a response to poly (ADP-ribose) polymerase (PARP) inhibitors or not.

Moore noted that outside of BRCA mutations, another biomarker is an assay assessing whether a tumor can fix its DNA. If the tumor is not able to fix its own DNA, it is referred to as homologous recombination deficient. Currently, there are 2 FDA-approved tests available for assessing this biomarker among women with ovarian cancer, which test the tumor and provide a score that defines a patient as homologous recombination deficient or homologous recombination proficient.

Moore noted that from 2018 to 2020 in the United States, there were multiple FDA approvals of PARP inhibitors in the front line after several studies demonstrated their efficacy in this setting. Today, when assessing whether use of a PARP inhibitor is appropriate or whether the risk to stratify is worth it, Moore explained that her answer is always to recommend to not overthink it.

Moore noted that when considering whether a PARP inhibitor is the appropriate approach or not, colleagues may comment on trials with data demonstrating remarkable progression-free survival following treatment without a PARP inhibitor. However, her response to being presented with these data is always to ask what the outcomes could have been if the patients had received a PARP inhibitor.

“If they had gotten a PARP, they would have done even better, and they might have been cured,” Moore said. “So, looking at a group of patients in the SOLO-1 trial—they are stage 3, primary site reduction, no gross residual, all BRCA—the best prognostic group you could ever hope to take care of with advanced ovarian cancer. You look at that control arm and those women are not cured.”

Moore noted that these data from the SOLO-1 trial highlight how, even with an excellent prognostic group, patients still benefit from the use of a PARP inhibitor.

“When you look at any of these subsets like we used to do with bevacizumab, such as high-risk, low-risk, new adjuvant, residual disease, no residual disease, age—they all are statistically significant and there’s not a group that is too high risk or too low risk if they meet other clinical parameters,” Moore said. “The bottom line is there’s not a group that doesn’t benefit from the use of a PARP inhibitor.”

REFERENCE

Moore K. Optimal Biomarker Evaluation and Management of Treatment-Naïve Advanced Ovarian Cancer. Society of Gynecologic Oncology 2022; March 19, 2022; Phoenix, AZ.