Individualized Approach Imperative in Frontline Ovarian Cancer

Ritu Salani, MD

The evolution of ovarian cancer treatment has introduced multiple frontline regimens that allow therapy to be given in various ways and tailored toward an individual patient, including in intravenous (IV), intraperitoneal (IP), and dose-dense forms, said Ritu Salani, MD. 

"The evolution of up-front chemotherapy has been complicated for ovarian cancer,” explained Salani. “In the 1990s, we started with carboplatin and paclitaxel. Today we are using the same regimen; however, there have been some tweaks in the routine and schedule in which we are giving it.”

Additionally, the choice on whether to give patients neoadjuvant chemotherapy or have them undergo primary debulking surgery is also personalized, Salani said.

However, she added that using PARP inhibitors in combination with chemotherapy could hold the key to changing the standard of care.

“The opportunities to combine targeted therapies with chemotherapy is exciting—if we can cure more patients while balancing toxicities,” said Salani.

In an interview  during the 2019 OncLive® State of the Science Summit™ on Ovarian Cancer, Salani, a gynecologic oncologist and associate professor at The Ohio State University Wexner Medical Center, discussed the evolution of up-front chemotherapy, as well as the roles of primary debulking surgery and neoadjuvant chemotherapy in ovarian cancer. 

OncLive:  What changes have occurred in frontline therapy for patients with ovarian cancer?

Salani: The real advantages have happened with maintenance therapy in other lines of therapy, but we have made strong progress in up-front therapy.

We have ideally addressed ways to provide better supportive care to minimize toxicities. In the up-front management of ovarian cancer, we have seen better selections of patients for neoadjuvant chemotherapy versus primary debulking surgery, and how to better tailor the medications for those patients. 

How do you decide between IV, IP, and dose-dense chemotherapy regimens for an individual patient with ovarian cancer?

The selection of chemotherapy is always challenging. The data we have seen are interesting, because there has been a strong drop-off in the role of IP chemotherapy. Part of that is due to the toxicities of the regimen, as well as the challenges of placing an IP port and catheter in a patient. Also, other data show that outcomes with IP chemotherapy may be comparable when you add bevacizumab (Avastin) to it or use other [dosing] schedules.

The route selection for each patient makes a difference. Studies have shown that some patients tolerate dose-dense chemotherapy better than the conventional every-3-week regimen, perhaps because of the adverse event profiles.

Scheduling convenience for patients is also a factor. Patients may be traveling from long distances, and coming every 3 weeks versus weekly may partially alleviate that burden.

What supportive care measures are available to alleviate the associated toxicities with chemotherapy?

In up-front chemotherapy, supportive medications include antiemetics, which are drugs we are better able to manage and potentially prevent a patient’s symptoms with. 

Also, different scheduling and dosing, along with the use of granulocyte-colony stimulating factor (G-CSF) medications, may can help [mitigate] neutropenia.

What factors do you currently consider when deciding if a patient should undergo primary debulking surgery or receive neoadjuvant chemotherapy? 

When considering a patient for neoadjuvant chemotherapy, there are several factors to think about. The first one is patient factors; is the patient medically fit to undergo a large operation? Typically, neoadjuvant chemotherapy is considered in the setting of advanced and large bulky disease—stage IIIC or stage IV.

If the patient can tolerate a large surgery, and I feel the patient is resectable to remove all visible disease—ideally, to no gross residual disease or <1 cm—surgery is the ideal choice.&#8239;

However, in unresectable patients, or where surgery will be a morbid procedure requiring bowel resections or radical operations, neoadjuvant chemotherapy may be an appropriate choice; surgery may be challenging for this type of patient to recover from. Also, if a patient has underlying comorbidities that may hinder them from having smooth recovery, I may recommend neoadjuvant chemotherapy.

Have any data highlighted efficacy or safety outcomes between neoadjuvant chemotherapy and primary debulking surgery?&#8239;

When you look at the outcomes between neoadjuvant chemotherapy and primary debulking surgery, the first primary endpoint is always survival outcomes. Across the board, survival outcomes have been generally the same for both groups. There are a couple flaws in the studies that people have challenged.

Still, individual selection is important rather than one-size-fits-all approach.&#8239;There has to be a little nuance in making that decision. The main difference comes down to surgical complications. When you are doing primary debulking surgery, the procedure is often more involved, so the complication rate is unsurprisingly higher.&#8239;If we choose the right patients, we can offer primary debulking surgery safely, but patient selection is key.&#8239;

What other treatments are on the horizon in this setting?

We've used carboplatin and paclitaxel as a backbone for several decades now. Recently the VELIA study, which was presented at the 2019 ESMO Congress, used the combination of a PARP inhibitor with chemotherapy [in the frontline setting].

Although the survival outcomes are questionable as to whether it was the maintenance veliparib or the frontline combination [of veliparib and chemotherapy that led to an improvement in PFS], the fact that we are able to combine therapies is of interest. The last time we were able to do that was with bevacizumab, and we saw some benefit in select patients.&#8239;