Ursula A. Matulonis, MD
Physicians are beginning to think about recurrent ovarian cancer differently, in terms of emerging therapeutic approaches, a refined focus on disease histology, and reevaluating the definition of platinum resistance, according to Ursula A. Matulonis, MD.
One such novel strategy was presented at the 2018 ESMO Congress. In a prospective phase III trial, the combination regimen of pegylated liposomal doxorubicin and carboplatin with bevacizumab (Avastin; CD-BEV) was found to significantly improve progression-free survival (PFS) versus carboplatin/gemcitabine and bevacizumab (CG-BEV) in patients with recurrent ovarian cancer whose first recurrence was ≥6 months following frontline platinum-based chemotherapy.
Results showed that the median PFS was 13.3 months (95% CI, 11.7-14.3) in patients randomized to CD-BEV versus 11.7 months (95% CI, 11.1-12.8) in patients treated with CG-BEV (HR, 0.807; 95% CI, 0.681-0.956; P
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Ovarian Cancer, Matulonis, chief, Division of Gynecologic Oncology at Dana-Farber Cancer Institute, professor of medicine at Harvard Medical School, highlighted available and emerging treatment options and strategies for patients with recurrent ovarian cancer.
OncLive®: How would you define the recurrent ovarian cancer setting?
: There are a lot of exciting things going on in this realm, so that is pretty exciting. There are new options for patients—options that are FDA approved. I focused mostly on those [in my presentation], and I gave some updates on new trials that may have been presented recently with exciting new drugs and new strategies to treat [patients with] recurrent ovarian cancer.
Could you highlight the available data on adding bevacizumab to standard chemotherapy?
I presented data on adding bevacizumab to standard chemotherapy—so either carboplatin/gemcitabine or carboplatin/pegylated liposomal doxorubicin for recurrent platinum-sensitive ovarian cancer. There was a trial presented at the 2018 ESMO Congress of carboplatin/pegylated liposomal doxorubicin/bevacizumab versus carboplatin/gemcitabine/bevacizumab. And, I reiterated older results of the AURELIA trial, which looked at the addition of bevacizumab to nonplatinum-based chemotherapy for patients with platinum-resistant cancer. These are not new data; we are thinking about recurrent ovarian cancer a little differently.
We have typically thought about platinum resistance as having a platinum-free interval for less than 6 months and platinum sensitivity for more than 6 months, but our paradigm is changing. We are thinking about patients who are appropriate and not appropriate for platinum-based therapy. Those definitions are probably definitely going to be seeping into our clinical trial eligibility, but they haven’t quite been defined that way yet. However, it’s a good way of thinking about it because there are patients who may be defined as platinum resistant in the true sense of how the definition was previously, who are really going to have platinum-sensitive disease.
Could you expand on the study that was presented at the 2018 ESMO Congress?
This was predominantly a European study that showed benefit to the carboplatin/pegylated liposomal doxorubicin/bevacizumab arm compared with carboplatin/gemcitabine/bevacizumab. The primary endpoint was PFS. The result was a little more striking for patients who had not received prior bevacizumab. For those who had received prior bevacizumab, there was a statistically significant difference but it wasn’t overwhelming.
How would you describe the potential of immunotherapy in this setting?
We do have 1 FDA approval of immunotherapy for women who have recurrent gynecologic cancers, and that is pembrolizumab (Keytruda). It’s a broad approval for patients who have microsatellite instability-high (MSI-H) cancers; we see that more in recurrent endometrial cancer and occasionally, we will find it in recurrent ovarian cancer. Most pathologists are not doing MSI testing, but a lot of the next-generation sequencing tests will look at MSI to sort of define a cancer as microsatellite proficient versus instable. Somatic tumor profiling might give you the sense that this patient may have an MSI-H tumor.
What are your thoughts on the JAVELIN Ovarian 200 trial of avelumab (Bavencio), in which the PD-L1 inhibitor missed the PFS endpoint?
This was a phase III study with a primary endpoint of PFS and overall survival looking at avelumab alone, pegylated liposomal doxorubicin by itself, or the combination. It did not meet its primary endpoints to show benefit of the combination over the single agents. We await final discussion of that data at [an upcoming medical] meeting, and then also final publication of the results.