Objectives

The primary objective of this study was to analyze the impact of comorbidities, postoperative complications and center volume on overall survival in a real-life cohort of ovarian cancer patients in France.

Methods

All French women aged 18 years or over, with ovarian cancer newly diagnosed between January 2013 and December 2019, registered in the general health insurance coverage plan were included in the cohort. Ovarian cancer treatments, comorbidities, postoperative complications and death were extracted from hospital discharge reports. The characteristics of the centers were also collected.

Results

We included 29,879 patients with ovarian cancer in the cohort. The median age was 66 [57-74] years, and 24,783 (82.9%) presented an advanced stage at diagnosis (FIGO IIB-IVB). A total of 16,048 (53.7%) patients had at least one comorbidity at the time of diagnosis, mainly hypertension (n=6,800) and obesity (n=2,505). Patients received primary surgery, interval surgery, or chemotherapy alone in 31.5%, 30.4%, and 38.1% of cases, respectively. A total of 3,031 (16.1%) patients presented a postoperative complication Clavien-Dindo III or more within 90 days of cytoreduction surgery, mainly digestive (60.4%). For advanced stages, the median overall survival was 47 [45.9-48] months. The number of comorbidities, the occurrence of a complication and low center volume had a significant negative impact on the overall survival.

Conclusions

Real-life data give the opportunity to study the key health indicators in ovarian cancer. A personalized care pathway should be a priority for patients with comorbidities and at risk of postoperative complications.

Objectives

Mirvetuximab soravtansine (MIRV) is a first-in-class ADC comprising a folate receptor-α (FRα)-binding antibody, cleavable linker, and maytansinoid DM4 payload. As part of the phase 1b/2 trial (NCT02606305), efficacy, safety, and tolerability of MIRV and bevacizumab (BEV) were evaluated in patients with recurrent FRα-positive ovarian cancer (OC) measured by immunohistochemistry (PS2+ ≥25%).

Methods

Patients received MIRV (6 mg/kg, adjusted ideal body weight) and BEV (15 mg/kg) intravenously on Day 1 of a 3-week cycle. Primary endpoint was confirmed ORR assessed by RECIST v1.1. Safety and tolerability of MIRV + BEV were secondary endpoints.

Results

Patients enrolled (N=126; median age 62 years) were heavily pretreated (46%, ≥3 prior therapies) and 75% were platinum resistant. Prior taxane, BEV, or PARPi treatment occurred in 98%, 52%, and 27%, respectively. Low, medium, and high FRα expression in patient tumors was 10%, 40%, and 49%, respectively.

MIRV demonstrated anti-tumor activity in the entire cohort (ORR 44%, mDOR 11.8 months, mPFS 8.2 months), with ORR of 58% in BEV-naïve and 32% in prior BEV (Table 1).

Grade 3+ treatment emergent adverse events (TEAEs) were low; common TEAEs (Grade 3+, all grade) included diarrhea (2%, 67%), nausea (2%, 59%), blurred vision (1%, 56%), fatigue (5%, 53%), and hypertension (17%, 33%).

Conclusions

MIRV and BEV demonstrated anti-tumor activity, regardless of prior BEV treatment, and should be considered in FRα-positive recurrent OC. A randomized phase 3 trial (GLORIOSA) will evaluate MIRV and BEV in the maintenance setting in patients with FRα-high platinum-sensitive OC.

Objectives

Clinical data across several solid tumors, including EC, suggests synergy between immune checkpoint inhibition and anti-angiogenic agents. This study sought to evaluate the efficacy and safety of Atezolizumab (A) and Bevacizumab (Bev) in recurrent EC.

Methods

This multicenter, single arm trial (NCT03526432) enrolled patients with recurrent EC (1-2 priors) to receive A 1,200mg and Bev 15 mg/kg day 1 every 21 days. The primary endpoint was overall response rate (ORR) and duration of response (DOR).

Results

There were 57 response evaluable patients who received both drugs for the first two cycles. Median age was 65 (25-91) years and race included 22.8% Black and 2% American Indian. 61% had endometrioid tumors, 18% UPSC or carcinosarcoma each and 4% clear cell. 87% were mismatch repair proficient (MMRp) and 13% MMRd. 15% had prior pelvic radiation. Adverse events and clinical activity in Table 1. Translational data including blood immune cell population analysis by CyTOF will be presented with the clinical data.

Conclusions

The ORR for A and Bev approximates that seen with Len/Pem with far fewer side effects. An ongoing trial within the Alliance contains this similar arm and if confirmatory would support this combination as a treatment option.

Objectives

In 2014, the FDA released a warning against the use of laparoscopic power morcellators in women undergoing myomectomy or hysterectomy for the treatment of uterine fibroids due to the risk of spreading unsuspected leiomyosarcoma. We proposed to describe the pattern of incidence and survival of leiomyosarcoma (LMS) before and after the FDA warning.

Methods

Incidence data were obtained from the United States Cancer Statistics (USCS) database from 2001-2018 and survival data were obtained from the National Cancer Database (NCDB) for diagnoses made between 2004-2016. Average annual percent change (AAPC) was calculated using Joinpoint regression.

Results

Using USCS data from 2001 to 2018, 16,808 cases of leiomyosarcoma were diagnosed (10,207 (60.7%) White, 3,773 (22.4%) Black, 1,924 (11.4%) Hispanic, 727 (4.3%) Asian/Pacific Islander). Prior to the FDA warning, from 2001 to 2014, the incidence of distant LMS increased 4.00% annually (p<0.05). After the FDA warning, from 2014 to 2018, the incidence of distant LMS decreased 4.67% annually (p<0.05). However, the incidence of local and regional LMS remained stable from 2001 to 2018 (AAPC 0.10 and 0.50 respectively, p>0.05). Using NCDB data, we divided the study group into diagnoses made during 3 time periods (2004-2007, 2008-2012, 2013-2016). The LMS 5-year survival rate remained unchanged at 36.62%, 36.77% and 36.46% respectively (p>0.05).

Conclusions

Since the FDA warning of the power morcellator in 2014, distant LMS has decreased 4.67% per year. The correlation of these findings to the FDA warning of power morcellators warrants further investigation.

Objectives

Early reports of PD-1 inhibition in ovarian clear cell carcinomas demonstrate promising durable response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent ovarian clear cell carcinomas.

Methods

This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and epacadostat orally 100 mg twice a day. Primary endpoint was overall response rate (ORR), with secondary endpoints of toxicity, progression-free survival (PFS) and overall survival (OS).

Results

Between September 28, 2018 and April 10, 2019, 14 patients accrued at first stage. Rate of accrual was 2.3 patients per month, higher than estimated. Median age was 65 (44-89), 10 (71.4%) had ≥ 2 prior regimens. ORR was 21% (95% CI 5-51%) within 7 months of study entry with 3 partial responses, 4 had stable disease for disease control rate of 50%. Median PFS was 4.8 months (95% CI: 1.9-9.6), OS 18.9 months (95% CI: 1.9-NR). Most common grade ≥ 3 adverse events reported were electrolyte changes and bowel obstruction. In July 2019, the study reached the pre-specified criteria to re-open to second stage, however after holding for amendment, the study closed prematurely in February 2021 due to insufficient drug supply.

Conclusions

Combination of pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent ovarian clear cell carcinomas. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with ovarian clear cell carcinomas.

Objectives

We sought to investigate if molecular profiles and endometrial cancer (EC)-based molecular subtyping are associated with clinicopathologic variables and outcomes in ovarian clear cell carcinomas (OCCCs).

Methods

Patients with OCCC who underwent clinical panel-based sequencing from 4/2015-1/2021 were identified. Pathogenic somatic alterations, EC molecular subtypes, clinicopathologic variables, and survival outcomes were obtained. Appropriate statistical methods were applied.

Results

Following central pathology review, 119 OCCCs were identified. Stage at diagnosis was equally distributed (54% I/II; 46% III/IV). Eighty-three percent (n=99) were copy number (CN)-low, 12% (n=14) were CN-high, 4% (n=5) were microsatellite instability (MSI)-high, and 1% (n=1) were POLE mutated. The most frequent genetic alterations were ARID1A (n=80, 67%), PIK3CA (n=56, 47%), TERT promoter (n=27, 23%), and PPP2R1A (n=19, 16%). ARID1A and TERT alterations were mutually exclusive (p=0.04, q=0.19). Endometriosis was significantly enriched in CN-low OCCCs (p=0.02), and patients diagnosed at <50 years of age were more likely to harbor PIK3CA alterations (p=0.04). In the entire cohort, multivariate analysis of outcome revealed that Asian race (p=0.04), advanced stage (p<0.01), and CN-high subtype (p=0.03) were significantly associated with worse progression-free survival; advanced stage (p=0.01) and PPP2R1A alterations (p=0.04) were significantly associated with worse overall survival. Univariate sensitivity analysis including only patients who had the initial treatment planning at our institution found the same survival associations.

Conclusions

OCCC is a heterogenous group of tumors with varied clinical outcomes and molecular profiles. In this retrospective series of OCCCs, race, EC-based molecular subtype, stage at diagnosis, and PPP2R1A alterations were predictive of outcome.

Objectives

The magnitude of adverse outcomes caused by the disrupted surgical cancer care during the COVID-19 pandemic is unclear. Our aim was to evaluate the changes in care and short-term outcomes of surgical patients with gynecological cancers during the initial phase of the COVID-19 pandemic internationally.

Methods

A multicenter, international prospective cohort study including consecutive patients with gynecological cancers who were initially planned for non-palliative surgery. Primary outcome: 30-day postoperative SARS-CoV-2 infection rate. Secondary outcomes: 30-day perioperative mortality and morbidity, COVID-19-related treatment modifications.

Results

We included 3973 patients (52 countries; 7 world regions). Lower-than-reported rate (22/3778; 0.6%) of perioperative SARS-CoV-2 infections was observed. This group had higher morbidity (63.6% vs 19.1%; p<0.0001) and mortality (18.2% vs 0.7%; p<0.0001), compared to the uninfected cohort.

In 20.7% (823/3973), standard of care was adjusted. Significant delay (>8 weeks) was observed in 11.2% (424/3784), particularly in those with ovarian cancer (213/1355; 15.7%). This delay was associated with a composite of adverse outcomes including disease progression and death (95/424; 22.4% versus 601/3360; 17.9%, p=0.024), compared to those who had operations within 8 weeks of their MDT decisions. One in thirteen did not receive their planned operations (189/2430; 7.9%), in whom 1 in 20 (5/189; 2.7%) died and 1 in 5 (34/189; 18%) experienced disease progression or death within 3 months of decisions for surgery.

Conclusions

One in five surgical patients with gynecological cancer worldwide experienced management modifications during the COVID-19 pandemic. Significant adverse outcomes were observed in those with delayed or cancelled operations- coordinated mitigating strategies are urgently needed.