Dennis R. Scribner Jr, MD
Recurrence marks a significant shift in the treatment of patients with ovarian cancer, in which it changes from a focus on cure to a focus on effective management, says Dennis R. Scribner Jr, MD. While PARP inhibitors have demonstrated impressive efficacy and tolerability and have helped streamline the process, there are many facets of effective care.
“I try and put it in this perspective: We can’t cure chronic issues like asthma, hypertension, or diabetes, but people live long and [full] lives with those medical issues; they can still maintain a very good quality of life [QoL],” says Scribner.
Molecular profiling will help identify patients who will reap the most benefit from available therapies. Although PARP inhibitors and chemotherapy have been shown to be vital to the management of the disease, Scribner insists that patient preferences should also be considered when choosing treatment.
“The science behind all of those variables is very important, but we sometimes lack an understanding of what patients have to go through in terms of their performance status, family and/ or personal issues, travel time to get to the doctor, and determining whether to take pills or come in to get chemotherapy.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Ovarian Cancer, Scribner, clinical associate professor, University of Arizona School of Medicine, Arizona Oncology, discussed the elements and evolution of treatment for patients with recurrent ovarian cancer.
OncLive: How would you define the current state of ovarian cancer?
: Our focus has been on developing clinical trials that will help women extend their lives and reduce adverse events (AEs). It’s difficult once patients recur, but we have several different therapeutic options that allow us to manage these patients for many years.
Everybody would agree that it’s complicated because it’s not just about the best drugs. In the recurrent setting, you have to take into account patients’ previous toxicities, the time from their last therapy, histology, molecular markers, molecular makeup, whether they are BRCA1/2-positive, and whether or not they have homologous recombination deficiency (HRD). You also have to look at the number of prior therapies they have received.
It’s a complicated but important conversation to have with patients so that they understand their options. They’re always going to ask, “What you would do?” You have to think about it as a management scheme so that if plan A doesn’t work, you have plans B and C in place.
We now have oral PARP inhibitors for patients in the recurrent setting who are on third- and fourth-line therapies. Now, we’re looking at them as maintenance therapy. There are a lot of checkpoint inhibitors [being explored]. It’s amazing that we now have drugs that allow our immune system to recognize cancer cells when, in the past, they were hidden by these receptors. Now, we can block them. I’m hopeful that this will take us to the next category of drugs that we can use to help these women.
What is the role of chemotherapy?
There is always going to be a role for chemotherapy. It becomes more convoluted when the response rates from chemotherapy are equal to or less than some of the PARP inhibitors, for example. Platinum-sensitive patients show astronomically high response rates to platinum-based drugs, in the 6- to 12-month or even 12-month-or-greater range.
We are never going to get away from chemotherapy. I’m hopeful that as we learn more about the molecular makeup and identify different variables within the tumors, we can better choose the best chemotherapy for each patient. The reason 2 patients with the same stage and histology can have very different responses to the same chemotherapy regimen has to do with molecular aspects of the disease, which we are just beginning to understand.
Molecular profiling allows us to identify particular markers and predict which drugs a patient will respond better to; it’s a much better way of tailoring individual treatment. The days of everyone getting a certain chemotherapy at a certain stage are no longer. You should be looking at the histology and molecular profile [of each patient] so that we can get better results.
Can you speak to the explosion of PARP inhibitors in this field?
PARP inhibitors came onto the scene several years ago after they were examined in phase II trials in the recurrent setting. Study 19 showed response rates of 35% with olaparib (Lynparza). We were giving etoposide pills a long time ago as a treatment for patients who were too sick to get chemotherapy. Now, oral cancer therapeutics have emerged as efficacious. The original phase II trials showed response rates that were equal to or sometimes better than chemotherapy in recurrent patients.