Two Analyses Describe Patient Preferences for Maintenance Therapy in Ovarian Cancer


In an interview with Targeted Oncology, Charlotte Sun, DrPH, MPH, discussed the findings from 2 abstracts from the 2020 SGO Annual Meeting on patient preferences for maintenance therapy in ovarian cancer and how these findings can be applied to practice in the community oncology setting.

Several options for maintenance therapy are currently available for the treatment of patients with ovarian cancer, which was the basis of a study to assess patient preferences for the potential side effects, decision-making factors, and quality versus quantity of life.

For ovarian cancer maintenance options, bevacizumab (Avastin) and PARP inhibitors are available based upon certain criteria, such as BRCA mutational status whether a patient has completed treatment for primary or recurrent disease, and sensitivity to platinum-based chemotherapy. Although it is still unknown whether maintenance therapy improves overall survival (OS), recent clinical trials have demonstrated an improvement in progression-free survival (PFS) for patients with ovarian cancer who receive maintenance therapy.

For patients who do not want to undergo maintenance therapy, they can opt for routine surveillance, which includes routine visits to their doctor every 3 months for a CA125 blood test and physical exam. For many patients, the decision between routine surveillance and maintenance therapy is a question of quantity versus quality of life.

Two analyses presented virtually for the 2020 Society of Gynecologic Oncology (SGO) Annual Meeting evaluated patient preferences in the maintenance setting for patients with ovarian cancer. Both abstracts focused on key factors that patients consider when making treatment decisions. Patients appeared to rely most on their physician’s recommendation and the effectiveness of the drug over other factors such as treatment schedule, need for supportive care medications, and indirect costs, among others. This finding was found across all subgroup analyses. Patients also were more likely to consider maintenance therapy over routine surveillance when the maintenance strategy involved oral therapy and notable gains in progression-free survival.

In an interview with Targeted Oncology, Charlotte Sun, DrPH, MPH, associate professor (research) in the Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas, discussed the findings from these 2 abstracts and how these findings can be applied to practice in the community oncology setting.

TARGETED ONCOLOGY: What are the treatment options in the maintenance setting for patients with ovarian cancer?

Sun: It depends on the patient has completed treatment for primary or recurrent disease. In the primary disease setting for BRCA-mutated patients who have completed treatment, there is a PARP inhibitor, and for non-BRCA-mutated patients, there is bevacizumab. In the recurrent setting for platinum-sensitive disease, bevacizumab or PARP inhibitors, are options.

TARGETED ONCOLOGY: What is the rationale for evaluating patient preferences in these abstracts?

Sun: Both of these abstracts come from our work as part of a larger study to design [make] a shared decision tool for women diagnosed with ovarian cancer who are considering maintenance therapy. The [goal] is to help them decide with their doctors and family members what patients value the most and things to consider before they decide whether or not they want to undergo maintenance therapy.

Maintenance therapy is typically presented as an option for women who have completed chemotherapy for their ovarian cancer and who have had a very good response to that chemotherapy. They can either opt for maintenance therapy such as PARP inhibitor or bevacizumab depending on the specific situation, or undergo routine surveillance, which means visiting their doctor every 3 months for a physical exam and CA125 test to monitor things and make sure that disease has not recurred.

Clinical trials of maintenance therapy involving bevacizumab and PARP inhibitors have demonstrated improvements in progression-free survival, so in other words it extends the amount of time that patients are without disease. Maintenance therapy is presented as an option to certain patients to try to increase the time in remission.

The challenge is that we still don’t know whether or not maintenance therapy improves overall survival. When women are deciding between maintenance therapy or routine surveillance, they are deciding between whether or not they want to take a therapy that has side effects that could impact their quality of life but could also extend the amount of time in remission, or take the more conservative route, which is to undergo routine surveillance. It is a choice between whether or not patients are willing to have additional therapy with the associated side effects for the chance of having a longer remission interval versus routine visits with their doctor for a CA125 blood test and physical exam but with no side effects because they are not taking any additional medication (or therapy).

We designed scenarios to help us understand the trade-offs patients are making when think about the choice between maintenance therapy or not, the factors that are most important to them, and how they are picking and choosing between quality of life versus quantity of life. 

TARGETED ONCOLOGY: Looking at the presentation on side effects and decision-making factors that are associated with maintenance therapy, what were the findings?

Sun: As part of that larger study, we had conducted qualitative interviews with patients to find out how they make treatment decisions and what goes into their decision-making process. One thing they talked a lot about was the factors that influenced them the most, including side effects. For the study in this abstract, 40 ovarian cancer patients rated health states which described various side effects associated with chemotherapy or maintenance therapies. They rated the side effect health states in order of most bothersome to least bothersome. We also asked patients to rank specific decision factors in order of importance (how influential these decision factors are) in their treatment decisions.

We found that the most unfavorable side effects were chronic wound healing, nausea and vomiting, and bowel perforation. To be clear, patients might not necessarily have experienced these side effects. Patients on this study had all received chemotherapy for primary or recurrent disease so they were very knowledgeable about treatment-related side-effects. 

The least bothersome of the side effects included thyroid issues and skin rash, followed by peripheral neuropathy. When we looked at different subgroups, we found there were no differences based on employment or income status. There were also no differences in terms of preferences based on the age of patients, or whether they had young children at home. We did see differences based on their level of education. Patients who were college-educated generally rated all of those side effects more favorably compared with patients with a high school education. In particular, women with less education rated the following side effects as significantly lower (less favorable) than more highly educated women: changes in how food tastes, concentration (chemo-brain), fatigue, and skin rash. Almost just as significantly, this group rated leg cramps and pneumonitis as more bothersome than women with college degrees.

We did see a few differences based on racial subgroups. With the exception of anemia and nausea, white women rated the side effects more favorably compared with women who were non-white, particularly for diarrhea and pneumonitis.

As far as the ranking of decision factors in order of importance, physician’s recommendation and the effectiveness of treatment were the 2 most important factors for patients making treatment decisions, followed by the side effects associated with a particular treatment. That was clear-cut across the board and did not change, no matter how we looked at the subgroups. What the doctor recommends and how well the treatment works are the 2 main factors that are going to drive patient decisions about treatment.

Things like out-of-pocket costs and indirect costs, such as paying for parking or extra gas to get to the hospital, and meals, tended to influence patient decision-making the least in our study. They were not perceived as important as the physician recommendation or effectiveness of the treatment. We also did not see any differences based on whether or not they had prior maintenance therapy, based on their marital status, whether young children were in the household, the number of people in the family, or whether or not they had ever gone on surveillance or not.

TARGETED ONCOLOGY: What were the most informative findings from this study?

Sun: For the side effects portion of that abstract, we found that whether or not patients had prior treatment with bevacizumab influenced how they rated the side effect descriptions. Patients who had prior treatment with bevacizumab (as maintenance therapy or for treatment for recurrent disease) rated anemia, hypertension, concentration, skin rash, and bowel perforation more favorably compared to patients who had never received bevacizumab.

For decision-making factors, non-white patients rated the following factors as more important in the decision-making process compared with white patients: treatment schedule, additional medications needed for side effects, out-of-pocket costs, and indirect costs. In other words, these factors were more influential for the treatment decisions of non-white patients compared to white patients.

We saw similar trends in education. Patients with lower education levels rated certain decision factors as more important compared to patients who had higher education. Such decision factors included the need for routine monitoring, treatment modality, treatment schedule, the need for additional medications to manage side effects, time away from work/daily activities, length of treatment visits, out-of-pocket costs, and indirect costs.

We noted these similar trends when evaluated the data based on patient employment status. Race, education level, and employment status are surrogate indicators of socioeconomic status. We believe certain socioeconomic subgroups may place higher importance on specific decision factors compare to other patient subgroups.

TARGETED ONCOLOGY: Looking at the other abstract evaluating patient preferences for maintenance therapy versus routine surveillance specifically in terms of gains in PFS and risks of adverse events (AEs), how was this analysis conducted?

Sun: This abstract was focused on how patients choose between quantity versus quality of life, so how patients make decisions about potentially longer disease-free intervals but having to experience side effects versus potentially disease-free intervals with better quality of life. We did something called a modified time trade-off, which is a way of evaluating quality versus quantity of life. We drew up 4 scenarios based on 4 key clinical trials for maintenance therapy. We used the maintenance strategies and PFS outcomes from SOLO1 and GOG218 for scenarios in the primary disease setting, and maintenance strategies and PFS outcomes from SOLO2 and GOG213 for scenarios in the recurrent disease setting. It’s important to say that for the scenarios in this second abstract, we did not factor in into account BRCA status into the scenarios.

40 ovarian cancer patients evaluated whether or not they preferred a longer disease-free interval on maintenance therapy with therapy-specific side effects versus routine surveillance with a potentially shorter disease-free interval. We found in the scenarios that included the PARP inhibitor, more patients were willing to consider taking the maintenance therapy, and in the scenarios that involved bevacizumab, fewer patients were willing to opt for the maintenance therapy.

TARGETED ONCOLOGY: Could you elaborate on these findings?

Sun: PARP inhibitors are an oral therapy while bevacizumab is an IV therapy, and both therapies have completely different side effect profiles. For the scenario involving a PARP inhibitor versus surveillance after completion of primary treatment, the PFS intervals were 50 months versus 14 months, respectively. We systematically decreased the amount of clinical benefit patients would have, and we asked them whether they would choose the maintenance strategy or surveillance at each time interval. We had visual props for the patients. This was done on an iPad so it was interactive, and we could show them visually how we were changing the different times in remission so they could see the relative differences in PFS between maintenance therapy vs surveillance. We found that in the 2 scenarios involving the PARP inhibitors after chemotherapy for primary and recurrent disease, more patients opted for maintenance therapy from the start and continued to choose maintenance therapy over surveillance even when the PFS gain was decreased to just 6 months. For the 2 scenarios that involved bevacizumab, far fewer patients chose maintenance therapy over surveillance given the modest gain in PFS. 

We also asked patients about their willingness to accept risks for developing certain rare but serious adverse events. The adverse events we looked at in this study were secondary blood cancer, ruptured bowel, or adrenal insufficiency. We used a modified standard gamble exercise which asked patients to choose between a potentially longer PFS with a maintenance therapy that had an associated risk of developing a serious adverse event or routine surveillance with a potentially shorter PFS with no side-effects. The probability of developing the serious adverse event was systematically varied, and at each interval patients were asked to whether they preferred maintenance therapy or routine surveillance. The probability was varied until patients were indifferent between maintenance therapy and routine surveillance. We were surprised at how high of a chance patients were willing accept in order to have a longer PFS over routine surveillance: 30% chance of developing a secondary blood cancer, 20% chance of developing a bowel perforation, and a 40% chance of developing renal insufficiency.

TARGETED ONCOLOGY: What is the main message for community oncologists to take away from this?

Sun: It is important for the community oncologists to understand what their patients value, for example do patients want to be off of treatment and not have any side effects, or do they desire to have more time without disease and tolerate side effects. Community oncologists know their patients pretty well, so they know things that matter the most to patients. Our data show that by far, patients place the highest importance on their physician’s opinion the most and effectiveness of the treatment. 

TARGETED ONCOLOGY: What are your final thoughts on these data?

Sun: We are taking this information and using it to build our decision tool for patients considering maintenance therapy. We have included an educational component in the tool so that patients can develop a better understanding of concepts such as PFS and OS, as well as risks of side effects. We are taking that into the next phase of development and will be conducting cognitive testing with patients in the near future.

The challenging part of decision-making for maintenance therapy is that we do not know whether or not it improves overall survival for patients. We do know; however, clinical trials have shown maintenance therapy improves the progression-free survival but there are side-effects associated with these therapies. If patients want a longer disease-free interval and they are willing to tolerate certain types of AEs, those patients would probably opt for maintenance therapy. That being said, we had patients on our study who said they would rather choose routine surveillance and have a shorter disease-free interval because they did not want any side effects (and wanted a better quality of life) rather than taking additional therapy with associated side-effects, even if this meant prolonging the disease-free interval.

The data were overall very informative because the field is changing rapidly. Hopefully, we will get some other clinical trial results in the near future, as well as additional approvals for other maintenance therapy options. 

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