Personalized Treatment Approaches Improve Outcomes for Patients With Ovarian Cancer
May 20, 2020 08:30pm
By Danielle Ternyila
Gynecologic oncology experts reflect on some of the most significant data presented during the 2019 SGO Annual Meeting, which underscored how the field is moving toward a precision medicine approach.
A common theme evident among the abstracts presented during the 2019 Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, held earlier this month in Honolulu, Hawaii, was matching the right treatment to the right patient at the right time, said Shannon Westin, MD, which is a foundation of precision medicine.
“To me, that was the overarching theme across all the different sessions…making sure they all get the right therapy so they can get the right outcome,” said Westin.
The meeting brought in experts throughout the field of gynecologic oncology, who presented their recent research for the treatment of women’s cancers, including endometrial cancer, cervical cancer, and ovarian cancer. Following the meeting, Targeted Oncologyspoke with experts in the field to discuss some of the most significant data that were presented, which showed a trend toward precision medicine.
“We’re getting better at how we deliver care as far as precision medicine is concerned, whether that be precision medicine from a targeted standpoint or precision medicine for overcoming disparities,” said Westin, an associate professor at The University of Texas MD Anderson Center.
“The most powerful study presented, in my opinion, was the study by Floor Backes, MD, and her colleagues. This was a pilot study in platinum-resistant ovarian cancer and recurrent endometrial cancer using chemotherapy and a targeted agent,” said Bobbie J. Rimel, MD, assistant professor of obstetrics and gynecology at Cedars-Sinai Medical Center.
In this phase I trial, patients with endometrial and platinum-resistant epithelial ovarian cancer were treated with the combination of lenvatinib (Lenvima), a tyrosine kinase inhibitor, and a weekly dose of paclitaxel. The results for this combination, presented by Backes, associate professor, Department of Obstetrics & Gynecology, College of Medicine, the Ohio State University Comprehensive Cancer Center, demonstrated promising activity in these 2 patient populations.
“Weekly paclitaxel has been used for these diseases for many years with a very modest response rate, but the addition of lenvatinib suggests a much more dramatic overall response rate (ORR) of 65%,” said Rimel. “That said, the toxicities of the combination are common and may become a limitation with this regimen in a larger population.”
The ORR was 71% in patients in the ovarian cancer group and 50% in patients with endometrial cancer. The primary objective was to identify a phase II dose of the combination. In addition, secondary endpoints included safety and tolerability, objective antitumor activity, progression-free survival, and pharmacokinetics.
In aninterview following her presentation, Backes shared her thoughtson the excitement surrounding the activity noted in endometrial and ovarian cancers in this trial.
“Every single patient but one saw a decrease in their tumor which is almost unheard of in this population. Even though it was a very small trial, the response rates are quite impressive,” said David M. O’Malley, MD, a professor in the department of obstetrics and gynecology at The Ohio State University Comprehensive Cancer Center.
Another trial Westin found particularly interesting at the meeting was an open-label phase II study evaluating the triplet regimen of pembrolizumab (Keytruda), bevacizumab (Avastin), and metronomic cyclophosphamide in patients with recurrent ovarian cancer. A 95% disease control rate and 40% ORR was reported at the meeting.
“I would say we are really starting to see some novel therapies,” Westin said. “We are starting to do the right combinations, and we are starting to see an impact, more so than with single-agent treatments. I think that this is something we’ve been expecting to happen, but it’s always good to see it in practice.”
In an analysis of the ongoing ENGOT-OV26/PRIMA study, there was a decrease in treatment-emergent adverse events (TEAEs) in patients with high-risk ovarian cancer that were treated with a 200 or 300 mg starting dose. These doses were based on an individual’s bodyweight and platelet count and was compared to patients who received a fixed dose of 300 mg.
"If a patient was greater than 77 kg or had a baseline platelet count greater than 150,000/μL they would start at 300 mg, but if they were underweight or had a low baseline platelet count, they were begun at 200 mg,” said Bradley Monk, MD, FACOG, FACS, professor and director of the Division of Gynecologic Oncology at Creighton University School of Medicine at St. Joseph's Hospital and Medical Center, Arizona Oncology, during his presentation at the 2019 SGO Annual Meeting.
In addition to decreased TEAEs, patients treated with the individualized dose also saw a decrease in grade 3 or higher hematologic toxicities, including an approximate 60% decrease in thrombocytopenia and 40% decrease in neutropenia. There was also an 80% reduction in grade 4 thrombocytopenia with the individualized dose.
"This was good to see because it further enforces the fact that you can safely give that drug at a lower dose with good efficacy, so it was exciting to confirm that," said Westin.
Results from the ongoing phase I/II GARNET trial demonstrated an ORR of almost 30% in patients with recurrent or advanced endometrial cancer treated with dostarlimab (TSR-042). These responses were seen in both microsatellite instability-high (MSI-H) and microsatellite stable (MSS) patients.
“This was very interesting because it’s a large number of patients, and the response rate in the MSS group was higher than has been previously reported. Response rates in the MSI-H were also higher than previously reported in smaller trials with checkpoint inhibitors,” O’Malley noted.
Dostarlimab is an investigational humanized PD-1 monoclonal antibody that inhibits the PD-1 receptor by blocking ligand binding. Significant clinical activity has been demonstrated in other tumor types with this agent as well.
“This particular medication has these patients responding who are the more heavily pretreated population,” O’Malley said. “This is a really interesting finding as a significant number of patients experienced clinical benefit and objective response rates.”
In the phase II innovaTV 201 trial, pretreated patients with recurrent or metastatic cervical cancer were treated with the antibody-drug conjugate tisotumab vedotin. Results presented at the meeting by David S. Hong, MD, deputy director of the department of investigational cancer therapeutics and associate vice president at The University of Texas MD Anderson Cancer Center, demonstrated that the agent was very active in this patient population.
“This population had little options in the metastatic setting after progression on chemotherapy combination, and to see a 30% to 40% response rate in that type of pretreated population was really exciting,” Westin said. “I personally had a patient that was on that trial, and she had a good result. It is good to see there was more than just my patient…it was nice to see they had good response rates across all the different patients.”
See more from the 2019 SGO Annual Meeting here.