Upfront Options Continue to Expand in Ovarian Cancer

Nisha Bansal, MD, associate professor of oncology and urology at Johns Hopkins Medicine

Nisha Bansal, MD

Intravenous (IV) chemotherapy is the traditional chemotherapeutic approach for first-line treatment of patients with ovarian cancer, but there are many facets that go into determining the best strategy, said Nisha Bansal, MD.

Moreover, the June 2018 FDA approval of bevacizumab (Avastin) combined with chemotherapy in this setting following initial surgery could change up the landscape even more.

The choice of chemotherapy depends on several factors, such as whether a patient has had optimal surgery with no evidence of visible disease, and whether they have undergone upfront surgery or received neoadjuvant chemotherapy.

Nevertheless, efforts continue to bring improved and less toxic options to patients with ovarian cancer, one of which is bevacizumab. The angiogenesis inhibitor’s most recent approval is for use in combination with carboplatin and paclitaxel, followed by bevacizumab monotherapy, for the treatment of women with advanced ovarian cancer following initial surgical resection.

The approval is based on findings from the phase III GOG-0218 trial, in which the bevacizumab regimen reduced the risk of disease progression or death by 38% versus chemotherapy alone. The median progression-free survival (PFS) was 18.2 months versus 12.0 months, respectively (HR, 0.62; 95% CI, 0.52-0.75; P <.0001).¹

Other trials have demonstrated the benefit of bevacizumab and were the basis for the drug’s initial approval for recurrent disease in 2014. In the OCEANS study, the median PFS with bevacizumab/chemotherapy versus placebo/chemotherapy in patients with platinum-sensitive recurrent ovarian cancer was 12.4 months versus 8.4 months, respectively (HR, 0.46; 95% CI, 0.37-0.58; P <.0001).² The benefit was likewise reflected in the phase III AURELIA trial in which combining the agent with chemotherapy induced a 62% reduction in the risk of disease progression or death compared with chemotherapy alone in patients with platinum-resistant recurrent ovarian cancer.³

OncLive: Please provide an overview of your presentation.

What are the scenarios in which the different types of chemotherapy administration may be most beneficial?

What patients are the most likely to benefit from dose-dense regimens?

Is there a preferred method of administration?

Does immunotherapy have a place in frontline treatment?

What about the role of PARP inhibitors in the frontline setting?

How have you incorporated bevacizumab into clinical practice?

Beyond bevacizumab, Bansal explained that heated intraperitoneal (IP) chemotherapy has garnered preliminary interest in the field and is being explored as an alternative therapeutic approach. In an interview during the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer, held just prior to the FDA approval of upfront bevacizumab, Bansal, a gynecologic oncologist at University of California, Los Angeles, discussed the evolving therapeutic paradigm of frontline approaches for patients with ovarian cancer.Bansal: There are different options for frontline therapy including IV chemotherapy, IP chemotherapy, and dose-dense IV chemotherapy. The choice of chemotherapy depends on several factors, such as whether or not the patient has had an optimal surgical effort to no gross visible disease, and whether the patient has undergone upfront surgery or neoadjuvant chemotherapy. These factors will also impact the treatment strategy. Traditional IV chemotherapy is administered with carboplatin and paclitaxel every 3 weeks for a total of 6 cycles. The other strategy for patients in the upfront setting who have been optimally cytoreduced is a combination of IV and IP chemotherapy. That is a very attractive option because it delivers the chemotherapy directly into the peritoneal cavity. It comes with significant toxicity, so it may not be suitable for more elderly or medically infirm patients. Another strategy would be a dose-dense treatment option. That seems to have a very good side effect profile and is well tolerated. However, we do not know if it is useful in all patients. We know it is helpful for our suboptimally debulked patients based on the data we have. Those patients should definitely be offered dose-dense therapy. We offer it for patients who have been optimally cytoreduced, as well. The traditional IV approach is still predominant throughout the country. However, both [IV and IP] are acceptable treatment strategies. That question is unknown at this time. In the absence of a clinical trial, I would not offer it. However, it is an interesting question that needs to be answered. The role of PARP inhibitors in upfront therapy is also uncertain. It is certainly an attractive treatment strategy for our BRCA-positive patients. Though the benefit is not yet known, it should be offered in combination [with another therapy] with a clinical trial. The clinical trials that we have so far have shown a modest benefit with the addition of bevacizumab. We know that it comes with a significant cost. It is very useful in the recurrent setting, especially in patients who have ascites.

What are some pivotal clinical trials in the field?

Based on the studies that we have now, the benefit of bevacizumab in the frontline setting has shown a very small advantage in PFS. Using it in the upfront setting has been limited in that regard. It is something that can be very useful in the recurrent setting.The trials that we have right now are very impactful, especially the recently published trials on heated IP chemotherapy. There are some interesting studies in the works regarding PARP inhibitors, as well. Those are anticipated.

What are the differences in toxicity between these 2 approaches?

What is an area of research that you would like to see addressed?

Heated chemotherapy differs in that it is a one-time temperature-warmed dose. The chemotherapy is instilled while the patient is having surgery in the operating room. The traditional IP chemotherapy is an outpatient delivery every week through a catheter.Patients who receive IP chemotherapy are getting repeated doses, so they may have more toxicity related to the subsequent doses. They are also awake for the administration. We need to further explore this question of heated IP chemotherapy and see whether there is a benefit to using it in patients who have had upfront surgery and who have had optimal cytoreduction.

References

1. FDA Approves Genentech’s Avastin (Bevacizumab) Plus Chemotherapy as a Treatment for Women With Advanced Ovarian Cancer Following Initial Surgery. Genentech. Published June 13, 2018. Accessed June 13, 2018. https://bit.ly/2JQiUIv.
2. Aghajanian C, Blank SV, Goff BA, et al. OCEANS: a randomized, double-blind, placebo-controlled phase iii trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer [published online April 23, 2012]. J Clin Oncol. 2012;30(17):2039-2045.
3. Pujade-Lauraine E, Hilpert F, Weber B, et al. AURELIA: A randomized phase III trial evaluating bevacizumab plus chemotherapy for platinum-resistant recurrent ovarian cancer. J Clin Oncol. 2012;30(suppl; abstr LBA5002).