Advancements in Targeted Therapies Revolutionize Ovarian Cancer Treatment

Eric Schroeder, MD

Traditionally, chemotherapies used in the treatment of ovarian cancer often affect healthy cells along with cancerous ones, leading to significant adverse effects among patients. However, more precise chemotherapies and targeted therapies have now enabled a more selective approach, homing in on cancer cells, according to Eric Schroeder, MD.

“Recent years have been exciting for ovarian cancer,” Schroeder, gynecologic oncologist at Baptist Health Miami Cancer Institute, told Targeted Oncology^TM in an interview. “With more recent chemotherapies and more targeted therapies and biologic agents, we have been able to affect the cancer cells more preferentially than the normal host cells, so that has been exciting.”

Not only has this new era of targeted therapies minimized adverse effects, but it has also opened doors to improved efficacy and patient outcomes for those with ovarian cancer.

In the interview, Schroeder discussed the transformative shift that the landscape of ovarian cancer treatment has undergone in recent years.

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Targeted Oncology: How has the evolution of ovarian cancer treatments evolved in recent years?

Schroeder: Recent years have been exciting for ovarian cancer. There has been the introduction of some new kinds of targeted therapies. For a long time, we used chemotherapies that are used in other disease sites as well, and they typically treat all the cells of the body. That is where you get a lot of the [adverse] effects from. With more recent chemotherapies and more targeted therapies and biologic agents, we have been able to affect the cancer cells more preferentially than the normal host cells, so that has been exciting.

The introduction of immunotherapy has been exciting. It has not panned out terribly well in ovarian cancer, not as well as in some of the other cancers, but still for some [patients], it does work. It has been a nice addition. I think more than anything is kind of a renewed interest and focus in research [with the] acceptance that we are nowhere near where we want to be. There are more products coming out, and there have been some regulatory changes which have allowed some products to come to market faster than then previously.

What are some of the drugs that have come into the playing field?

The first kind of targeted therapy we used was bevacizumab [Avastin]. That is an antiangiogenic agent. It was shown to help the chemotherapy that we were currently giving work better. Moving past that, and probably the next exciting thing that came along were the [poly-ADP ribose polymerase (PARP)] inhibitors. This maybe was the first real kind of targeted therapy, so this uses a mechanism that is deficient in some [patients] with ovarian cancer and exploits that. It has increased both progression-free survival and overall survival significantly, especially in the population that it was designed to work in. There has been some data that works in [women], even those who do not have those mutations, but certainly works best [in patients] who do. This moved the needle for the first time in a long time in a very meaningful way.

More recently, [there are some] more targeted agents for patients who in the past had relapsed or recurred after multiple lines of chemotherapy and other treatments who in the past did not have any other options. Most notably, antibody drug conjugates or ADCs, and mirvetuximab [soravtansine; Elahere] is 1 of those that is targeting specific receptors on ovarian cancer cells and delivering the chemotherapy just to those cells that have that receptor. That has been exciting. Again, immunotherapy has not panned out to be like a one-stop shop, fixing everybody with ovarian cancer like we had hoped it would be, but in the [patients] who have markers for that would suggest that the immunotherapy would work, there have been some exciting and encouraging results.

Are there any ongoing studies or trials that are currently kind of eye catching in space?

There are a lot of trials in the space. Currently, there are a number of trials trying to see if combinations of the things that I mentioned might work better than the drug alone. Maybe pairing an ADC with a PARP inhibitor or pairing immunotherapy with PARP inhibition to see if the combination could work better. I would say most of the trials that were successful have spurred a new trial to see if it can be more successful, usually with a combination of some of those drugs. I think ADCs are a huge area now, and probably in all of oncology, but certainly in gynecology. There are a number of companies looking at different receptors that are more common in ovarian cancer, then trying to design an ADC around that. Immunotherapy continues to be exciting. I think there are going to be more ways to kind of turn these tumors more susceptible to immunotherapies than they were just off the bat.

What unmet needs to exist in the space?

The big unmet need is we still don't cure most of these [patients]. Unfortunately, the numbers show that about 70% to 75% of these [patients] present in stage III or IV, and of those [patients], 70% to 75% of them will not be cured. [Those are] pretty bad numbers, maybe not compared with some other cancers, but certainly we do much better than that with some of the other cancers we treat. We need to do a lot better than we currently have. Obviously, whether that is combinations of what we currently have, or brand new ways of looking at things, which are also constantly being looked at.

The other unmet need I would say is, unlike breast cancer, for instance, we do not have a good screening test. These [patients] present in stage III and IV because we don't catch it in stage I and II. There is no real screening test currently available. There are some kinds of guidelines and we follow with ultrasounds, etc, but those are not catching stage I and II disease, and certainly not catching any kind of precancer. There are some exciting things going on with blood tests and looking at different markers and circulating DNA and free cancer cells, etc. I think that, hopefully not in the too-distant future, we will have a better way to say that these patients are heading in that direction and we will see if we can catch something closer to a precancer like we can with pap smears for cervical cancer.

What should other community oncologists know about treating patients with gynecologic cancers?

I would encourage anybody to enroll patients in clinical trials when available. That is sometimes difficult to do. Sometimes patients cannot travel [or] they don't want to take on extra testing or extra costs, but I would encourage them to just be aware of the area, whether it's here or 1 of the other hospitals in the area. Clinical trials are the way forward for sure. We are not where we want to be yet, and the only way forward to get closer to where we want to be is with clinical trials. I try to put aside my own biases, and if there is a clinical trial available, I try to put patients in it. At our center, we try to open more clinical trials.