Objectives

In OReO/ENGOT-ov38 (NCT03106987), maintenance olaparib rechallenge significantly improved progression-free survival (PFS) versus placebo in platinumsensitive relapsed ovarian cancer (PSROC), irrespective of BRCA1/BRCA2 mutation (BRCAm) status (BRCAm: hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.37–0.87; P=0.022; non-BRCAm: HR 0.43, 95% CI 0.26–0.71; P=0.002) (PujadeLauraine et al. ESMO 2021). We assessed health-related quality of life (HRQoL) by patient-reported outcomes (PROs).

Methods

Patients with PSROC, prior PARP inhibitor maintenance (one line), and in response to last platinum-based chemotherapy were randomized (BRCAm and non-BRCAm cohorts) to maintenance olaparib (300mg bid) or placebo until progression. Prespecified secondary PROs included change from baseline in Functional Assessment of Cancer Therapy–Ovarian (FACT-O) Trial Outcome Index (TOI), and best response and improvement in TOI. The minimally important difference (MID) for clinically meaningful change in TOI was 10 points.

Results

Patients were randomized in cohorts (BRCAm: olaparib=74, placebo=38; non-BRCAm: olaparib=72, placebo=36). The difference between olaparib and placebo in the overall adjusted mean change in TOI score was not considered clinically meaningful in either cohort as 95% CIs lay within the MID interval: BRCAm, -2.94 (95% CI -4.99 to -0.90); non-BRCAm, -2.66 (95% CI -4.75 to -0.58) (Figure). Most olaparib and placebo patients had a best response of no change in TOI; no significant differences in proportion with improvement in TOI were observed (Table). Few olaparib and placebo patients had a TOI deterioration: BRCAm, 10 (14%) and 4 (11%); non-BRCAm, 10 (15%) and 2 (6%).

Conclusions

Maintenance olaparib rechallenge significantly improved PFS over placebo, without clinically meaningful change in HRQoL.

Clinical trial ID: NCT03106987

Objectives

In ATHENA–MONO (NCT03522246), progression-free survival (PFS) improved with first-line rucaparib maintenance treatment vs placebo in patients with advanced ovarian cancer (OC), regardless of molecular characteristics (median PFS: 20.2 vs 9.2 months, log-rank P<0.0001; hazard ratio: 0.52; 95% CI: 0.40–0.68). Patients with or without high-risk clinical characteristics for disease progression were enrolled; in this subgroup analysis, we investigated whether all patients benefited from rucaparib first-line maintenance treatment, including those with more favorable baseline prognostic factors.

Methods

Patients with high-grade, FIGO stage III–IV OC who completed cytoreductive surgery and 4–8 cycles of first-line platinum-doublet chemotherapy with a response were randomized 4:1 to oral rucaparib 600 mg BID or placebo. Investigator-assessed PFS was evaluated in subgroups based on FIGO stage, timing of surgery, and residual disease status post-chemotherapy.

Results

As of Mar 23, 2022 (data cutoff), 427 and 111 patients were randomized to rucaparib monotherapy or placebo. Most patients had FIGO stage III disease (75%); approximately half underwent primary surgery (49%), and most had no residual disease (75%). In the intent-to-treat population, PFS improved with rucaparib vs placebo across all subgroups based on FIGO stage, timing of surgery, and residual disease (Table).

Conclusions

In the intent-to-treat population, first-line rucaparib maintenance treatment improved PFS vs placebo across subgroups regardless of timing of surgery or prognostic disease characteristics such as FIGO stage or residual disease. These results confirm rucaparib as a new effective maintenance treatment for OC patients with or without high-risk factors for progression at baseline, irrespective of molecular characteristics.

Objectives

The OVHIPEC-1 trial demonstrated improved recurrence-free and overall survival with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery (CRS) in patients with stage III epithelial ovarian cancer (EOC). In 2019, HIPEC for this patient population was implemented in ten Dutch HIPEC-centers. This study aimed to examine the use and early postoperative outcomes of HIPEC in a real-world setting.

Methods

This observational multicenter study used data from the Dutch Gynaecological Oncology Audit including all 668 Dutch patients with stage III EOC who underwent complete or optimal interval CRS between 2019-2021. We examined use of HIPEC and compared early postoperative outcomes with and without HIPEC while accounting for differences in baseline characteristics.

Results

During the study period, HIPEC use increased from 49% to 64%. Uptake varied between geographical regions from 40%-76%. Age, performance status, and result of CRS were associated with HIPEC use (Table 1). Early postoperative outcomes are shown in Table 2. In multivariable logistic regression analysis, HIPEC was associated with a prolonged length of hospital stay (>7 days) (OR 3.9, 95% CI 2.5-5.3, p<0.001) and increased complications (any complication) (OR 1.5, 95% CI 1.0-2.1, p=0.026). However, no effect was seen on incidence of severe complications (Clavien-Dindo ≥grade 3) (OR 0.7, 95% CI 0.3-1.5, p=0.378) and 30-day-mortality.

Conclusions

Use of HIPEC increased substantially in the Netherlands since its introduction in 2019. The effect of HIPEC on early postoperative outcomes in a real-world setting and clinical trial setting are comparable. Future analyses will show whether this also accounts for survival outcomes.

Objectives

Mirvetuximab soravtansine (MIRV) is a first-in-class ADC comprising a folate receptor α (FRα)-binding antibody, cleavable linker, and maytansinoid DM4 payload. Here, we present updated data from the single-arm study SORAYA on the clinical benefit and safety of MIRV in FRα-high platinum-resistant ovarian cancer (PROC).

Methods

Patients (N=106) received MIRV 6 mg/kg, adjusted ideal body weight, intravenously on Day 1 of a 3-week cycle. Patients must have received 1-3 prior therapies, including bevacizumab. FRα-high expression by immunohistochemistry (PS2+ ≥75%) was required. Responses were assessed by investigator using RECIST v1.1. Here we report tumor reduction and disease control rate (percent of patients with complete response, partial response, and stable disease of 12+ weeks).

Results

Characteristics of 106 patients enrolled are in Table 1.

Seventy-five patients (71%) experienced tumor reduction as their best response (Figure 1) and the disease control rate (DCR) was 51.4% (95% CI 41.5, 61.3). The confirmed ORR was 32.4% (95% CI 23.6, 42.2), the median duration of response was 6.9 months (95% CI 5.6, 8.1), and the median progression-free survival was 4.3 months (95% CI 3.7, 5.1).

Most frequent treatment-related adverse events (TRAE; all, grade 3+) related to study drug included blurred vision (41%, 6%), keratopathy (36%, 9%), nausea (29%, 0%), and dry eye (23%, 2%). Seven percent of patients discontinued treatment due to a TRAE.

Conclusions

MIRV demonstrated anti-tumor activity by tumor reduction and DCR in heavily pretreated patients with FRα-high PROC. These data support MIRV as a potential practice-changing, biomarker-driven therapy.

Objectives

Epithelial ovarian cancer (EOC) is the most lethal gynaecological cancer. In 2016, the Piedmont and Valle d’Aosta Oncology Network started on an Audit and Feedback (A&F) intervention to improve the quality and equity of care for ovarian cancer patients treated in Piedmont.

Methods

All consecutive patients treated in 34 centres from May 2016 to August 2020 for newly diagnosed EOC were included. A dedicated web database was created and data quality was centrally monitored. The treating hospitals were classified according to the mean yearly volume of surgical activity (≥35; 34-18; <18 patients). The adherence to previous selected indicators was classified as: high (>75%), medium (75-60%) and low (<60%). Overall survival (OS) was analysed with a multivariable Cox model including prognostic factors, hospital volume of activity and level of adherence to process indicators.

Results

The present analysis includes 1095 patients with EOC (23.4% early stages, 76.6% advanced). Out of 12 analysed indicators, 4 showed a high level of adherence, 3 a medium level and 5 a low level (Fig.1). In general, there was a lower adherence to guidelines by centres with a low volume of activity. For most of the indicators there was an improvement over time. Adherence to guidelines was associated to better OS after adjustment for prognostic factors.

Conclusions

The A&F intervention was useful to support the identification of reference centres, to promote centralization, to reduce variability among regional hospitals and to increase the appropriateness of treatment. Adherence to guideline recommendations was associated to a better outcome.

Objectives

Given the platinum sensitivity of BRCA 1/2-mutated high-grade serous ovarian cancers (HGSC), there is uncertainty about the relative benefits of primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy (NACT) in this population. We aimed to compare the long-term survival outcomes for women with germline or somatic BRCA mutations with HGSC undergoing either PCS or NACT.

Methods

We conducted a retrospective cohort study of BRCA-associated HGSCs treated with PCS or NACT at a tertiary cancer center between 1991-2020. All patients had confirmed germline or somatic BRCA mutations. Demographics, disease burden, surgical complexity and ten-year overall survival (OS)/recurrence free survival (RFS) were examined.

Results

Of 361 women with germline/somatic BRCA mutations, 240 (66%) underwent PCS and 121 (34%) underwent NACT followed by interval cytoreduction (IDS). Those undergoing PCS were younger (54 vs. 57; p<0.001), but there were no differences in functional status or underlying comorbidities. Initial disease burden was lower in PCS cohort, but surgical complexity was higher. The rate of complete cytoreduction was similar in both groups (22% vs 31%; p=0.120) as well as the rate of Poly (ADP-ribose) polymerase (PARP) inhibitor use (35% vs 32%; p=0.68). The 10-year OS and RFS were superior in PCS cohort (OS 54% vs 25%; p<0.001 and RFS 30% vs 10%; p<0.001). After controlling for CA-125 level, stage, length of cytoreduction, disease burden and surgical complexity, PCS remained as a significant predictor of improved OS (HR 0.46; p=0.002) and RFS (HR 0.56; p=0.004).

Conclusions

PCS leads to superior survival outcomes compared to NACT in women with BRCA-associated HGSC.

Objectives

The benefit of lymph node surgery (LNS) in early-stage endometrioid ovarian carcinoma (ENOC) is unknown. Only vague data on impact of endometrioid histotype is available. Prior studies examining the benefit of LNS in ENOC have been hampered by small numbers, and large-scale studies that consider modern classification are needed.

Methods

After launching a transatlantic initiative, a cohort of 785 ENOC was assembled from 22 centers across Canada and Europe. Histotype was confirmed by central expert pathology review and immunohistochemistry, followed by extensive chart review. Complete lymphadenectomy was defined as such when at least 10 pelvic and 10 paraaortic LN were removed.

Results

Chart review and histopathologic data was available from 596 patients of which in 509(85.4%) cases tumor spread was confined to the pelvis (pT1a-pT2b,M0). Grade distribution included 221/509(43.4%) G1, 212/509(41.7%) G2 and 74/509(14.5%) G3 tumors. While LNS has been omitted in 239/509(47.0%) cases, complete pelvic and paraaortic LNS was performed in 77/509(15.1%) patients. LNS was restricted to pelvic nodes in 88/509(17.3%), to paraaortic nodes in 16/509(3.1%) and to sampling procedures in 77/509(15.1%) cases. Positive nodes were found in 6/509(1.2%) patients with early-stage ENOC, all low-grade tumors were found to be node negative.

Conclusions

LEOPARD results indicate that lymph node involvement is rare in early-stage ENOC, even in high grade tumors. However, the variation in lymph node surgical practice was profound. Our team initiative stands to provide a powerful statement on the value of LNS, possibly improving precision care for ENOC patients.