The 2018 Society of Gynecologic Oncology (SGO) annual meeting not only had a record attendance of >2000 attendees, but also had several noteworthy abstracts that presented important therapeutic advances in ovarian and endometrial cancer using immune-oncology drugs, poly (ADP ribose) polymerase (PARP) inhibitors, as well as other targeted agents.
1) Dr. Panagiotis Konstantinopoulos from the Dana-Farber Cancer Institute, for instance, presented the TOPACIO study data specifically for platinum resistant ovarian cancer patients. This trial tested the combination of pembrolizumab, a monoclonal antibody which targets the checkpoint protein PD-1 and the PARP inhibitor niraparib in 62 patients with ovarian cancer that was resistant to platinum chemotherapy. The investigators found that the drug pair produced complete or partial responses in 25 percent of all ovarian cancer patients in this study. This overall response rate compares to response rates of less than 5 percent in similar patients treated with PARP inhibitors alone, and in approximately 11 percent in patients with ovarian cancer treated with pembrolizumab alone. Additionally, the response rate of this combination in patients with BRCA wild-type ovarian cancer was 26% which was particularly noteworthy. Many of the patients were heavily pretreated and some participants had received up to five previous treatments; more than half had already been treated with bevacizumab.
2) Dr. Matulonis presented noteworthy results of the combination of mirvetuximab soravtansine, an antibody drug conjugate against the folate receptor alpha, and pembrolizumab, PD-1 inhibitor, in platinum resistant ovarian cancer. In this abstract, the data on 14 patients was presented; the mean number of prior regimens was 4.5, so the patient population treated was heavily pretreated. The combination of mirvetuximab soravtansine and pembrolizumab was well tolerated with no unexpected toxicities occurring. The overall response rate was 43% for all patients, and was 63% in patients whose tumors tested medium/high folate receptor alpha expression. For the patients with medium/high tumor expression of folate receptor alpha, the median progression free survival was 8.6 months, and the duration of treatment response was 8.3 months. This data thus supports enrolling additional patients into this study that is testing with medium/high tumor folate receptor alpha expression.
3) Dr. Drew presented data of germline BRCA-mutated, platinum sensitive recurrent ovarian cancer in the MEDIOLA study which is a phase II basket study of the PARP inhibitor olaparib and the anti-PD-L1 antibody durvalumab. Thirty-four patients were enrolled and treated, the combination was well tolerated, and the Disease control rate (DCR) was 81%. The overall response rate in the whole cohort was 72%, and was 77% in patients with one prior line of therapy. Also interestingly, baseline PDL1 expression and tumor infiltrating lymphocytes did not appear to correlate with clinical outcomes. The presenting author stated that evaluation of the durvalumab/olaparib combination in first-line therapy in ovarian cancer will be tested in the global phase III DUO-O trial which is expected to begin by mid-year 2018.
4) Dr. Brian Slomovitz from the University of Miami presented phase II results comparing everolimus and letrozole or hormonal therapy with combined medroxyprogesterone acetate/tamoxifen in women with advanced or recurrent endometrial carcinoma. Seventy-four patients were enrolled; responses were observed in 24% of patients receiving everolimus/letrozole and 22% of patients receiving medroxyprogesterone acetate/tamoxifen. In the patients with no prior chemotherapy, response rates for everolimus/letrozole arm was 53% and 43% for the medroxyprogesterone acetate/tamoxifen arm. PFS was 6. 4 months in the everolimus and letrozole arm and 3.8 months in the medroxyprogesterone acetate/tamoxifen arm. More patients in the medroxyprogesterone acetate/tamoxifen arm (8.3%) had grade 3 or 4 thromboembolic events while 0% did in the everolimus and letrozole arm, though this difference was not statistically significant.
5) Dr. Mansoor Mirza presented retrospectively analyzed data pertaining to the NOVA study which randomized patients with platinum sensitive recurrent ovarian cancer in response to platinum to either the PARP inhibitor niraparib or placebo. Efficacy results have already been published in the New England Journal of Medicine in 2016 demonstrating significant PFS improvement in all 3 primary populations tested (germline BRCA+, HRD+/germline BRCA negative, and overall non-germline BRCA). This abstract presented data pertaining to predictive clinical features for early dose modification from _grade 3 thrombocytopenia, and these predictive factors included weight <77kg or baseline platelet count of <150,000/_l. The estimated PFS probability by dose level assessed after month 3 was similar, and dose reduction from 300 mg did not appear to compromise efficacy in this retrospective analysis according to the presentation. This data should help clinicians better manage the thrombocytopenia with niraparib.
6) Phase II data testing the PD-L1 inhibitor avelumab in recurrent endometrial cancer was presented by Dr. Konstantinopoulos from the Dana-Farber Cancer Institute. The trial design was 2 stage cohort design, and 2 patient cohorts with recurrent endometrial cancer were studied: microsatellite stable (MSS) cohort and microsatellite instable (MSI) and polymerase epsilon (POLE) mutated cohort. There were co-primary endpoints measured in this study including progression free survival for at least 6 months after initiating therapy and objective response rate by RECIST 1.1. Overall response rates for the MSS cohort was 6.3% and PFS6 was 6.3%, which did not meet criteria to move to the 2nd stage for the MSS cohort. In the MSI/POLE cohort, overall response rate was 21.4% and PFS6 was 33.3%, these results meeting criteria to move to the 2nd stage. All of the responses and PFS6’s occurred in patients with 3 lines or more of prior cytotoxic chemotherapy. Avelumab was well tolerated with no unexpected adverse events in this population.
7) Dr. Matulonis from the Dana-Farber Cancer Institute presented results of a phase II study testing the combination of pembrolizumab and pegylated liposomal doxorubicin (PLD) in platinum resistant ovarian cancer. Twenty six patients were enrolled, and the primary objective of this study was clinical benefit rate (CBR) (comprised of RECIST 1.1 confirmed complete and partial responses in addition to stable disease lasting at least 24 weeks). Approximately 80% of patients had received 1 or 2 prior lines of treatment. The overall CBR was 42.3% with 19.2% partial responses and 23.2% stable diseases lasting at least 24 weeks. With 11 pts meeting CB, this met a predefined statistical milestone to call the combination worthy of further study. Overall, the regimen was well tolerated with no grade 5 toxicities and very few grade 4 toxicities.
8) Drs. Fader and Santin presented data testing the combination of standard carboplatin and paclitaxel versus carboplatin/paclitaxel/trastuzumab in newly diagnosed or recurrent HER2+ serous cancer of the endometrium. The median PFS increased from 8.0 months with carboplatin and paclitaxel to 12.6 months with the addition of trastuzumab to carboplatin/paclitaxel. Patients with more advanced disease had almost a twofold increase in median PFS from 9.3 months with chemotherapy to 17.9 months with chemotherapy plus trastuzumab. Patients who were treated for primary cancer (41 patients) had a median PFS of 17.9 months in the chemotherapy plus trastuzumab arm vs 9.3 in the carboplatin/paclitaxel alone arm. For patients with recurrent serous cancer of the endometrium which was 17 patients, the median PFS was 9.2 months versus 6 months in the chemotherapy alone arm. Additionally, the combination of carboplatin/paclitaxel/trastuzumab was very well tolerated. This is certainly very important data on a very hard to treat cancer.
Ursula Matulonis, MD is the director and program leader, Gynecologic Oncology and the Brock-Wilson Family Chair at the Dana-Farber Cancer Institute.
