Gynecologic Cancer Intergroup Research Articles

3rd International Arabic Women’s Cancer Days & 6th Gynecologic Cancer InterGroup (GCIG) – Cervix Cancer Research Network (CCRN) Symposium 2024 in Morocco

3rd International Arabic Women’s Cancer Days & 6th Gynecologic Cancer InterGroup (GCIG) – Cervix Cancer Research Network (CCRN) Symposium 2024 in Morocco

How long is long enough? An international survey exploring practice variations on the recommended duration of maintenance therapy with PARP inhibitors in patients with platinum sensitive recurrent ovarian cancer and long-term outcomes

ObjectiveThere are no data, and thus no consensus, on the optimal duration of poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy for exceptional responders (here defined as progression-free for 5 years or...

From the Beginning of the Korean Gynecologic Oncology Group to the Present and Next Steps.

The Korean Gynecologic Oncology Group (KGOG) was established in 2002 and is the only organization in Korea conducting multi-center clinical trials for gynecologic cancers. Since its re-establishment as a non-profit organization in 2021, KGOG has grown significantly, now including 207 gynecologic oncology specialists from 76 hospitals. This growth is a testament to the dedication and hard work of all those involved in the organization. KGOG is committed to maximizing the activation of multi-center clinical research through policies that support patients with rare diseases and gynecologic cancer research, focusing on strengthening institutional capacity, equalizing participation opportunities, and enhancing information sharing. A significant milestone for KGOG was becoming a member of the US Gynecologic Oncology Group (GOG) in 2005, allowing participation in GOG clinical trials. KGOG later joined the Gynecologic Cancer InterGroup (GCIG) and strengthened its capabilities by hosting the first Endometrial Cancer Consensus Conference-Clinical Research (ECCC-CR) in 2023. KGOG holds biannual meetings and symposia, as well as 224 operating committee meetings annually to review the discussions of the Tumor Site Committee. KGOG has conducted 156 investigator-initiated trial (IIT) or sponsor-initiated trial (SIT) studies as KGOG-led or participated in research. Currently, 18 studies are registered, and 10 are in preparation. To date, 68 papers have been published. KGOG conducts six national projects and collaborates with external organizations such as the NRG Oncology Foundation, Gynecologic Oncology Group Partners (GOG-P), GCIG, East Asian Gynecologic Oncology Trial group (EAGOT), and the Japanese Gynecologic Oncology Group (JGOG). Through collaboration with renowned international research institutions, KGOG has significantly expanded the scope of its research, achieving noteworthy clinical outcomes. This report not only introduces the history and recent status of KGOG but also presents the exciting future direction of the organization, filled with potential breakthroughs and advancements in gynecologic oncology research.

Gynecologic Cancer InterGroup CA125 response has a high negative predictive value for CHK1 inhibitor RECIST response in recurrent ovarian cancer

We investigated the association of CA125 response with prognosis and RECIST response/progressive disease (PD) criteria in recurrent high grade serous ovarian cancer (HGSOC) patients treated with a cell cycle checkpoint kinase 1 inhibitor (CHK1i), prexasertib. 81 patients had measurable disease per RECISTv1.1, of which 72 and 70 were measurable by Gynecologic Cancer InterGroup (GCIG) CA125 response and PD criteria, respectively. Univariate and multivariate analyses showed that GCIG CA125 response (n = 32) is associated with improved progression-free survival (PFS) and overall survival (OS) compared to no GCIG CA125 response (n = 40) (median PFS 8.0 vs. 3.5 months [HR: 0.30, 95% CI: 0.18–0.51, p < 0.0001]; median OS 19.8 vs. 10.0 months [HR: 0.38, 95% CI: 0.23–0.64, p < 0.001]) independent of BRCA mutation status, platinum-sensitivity, previous PARP inhibitor therapy, ECOG performance status, and FIGO stage. Notably, GCIG CA125 response had a high negative predictive value (NPV: 93%, 95% CI: 80–98), but poor positive predictive value (PPV: 53%, 95% CI: 35–71) in predicting RECIST response. CA125 PD criteria also showed poor concordance with RECIST PD (PPV 56%, 95% CI: 40–71; NPV 33%, 95% CI: 17–54). Therefore, serum CA125 may be useful as a highly accessible prognostic and predictive biomarker to CHK1i therapy in recurrent HGSOC.

Study on the efficacy and toxicity of pamiparib combined with tamoxifen in the treatment of patients with epithelial ovarian cancer with biochemical recurrence during first-line PARPi maintenance therapy.

TPS5621 Background: A high proportion of ovarian cancer patients tend to have elevated CA-125 1-6 months before imaging recurrence. The time between biochemical recurrence (i.e., only elevated CA-125 without imaging finding or clinical symptoms) to imaging recurrence can be considered a "window period", and if the “window period” can be extended, it may convert platinum-resistant relapsed patients to platinum-sensitive patients, and ultimately improving patient outcomes. The timing of treatment for the biochemical recurrent patients has been controversial. Tamoxifen, an anti-estrogenic drug, is considered an effective option for these patients. Pamiparib (BGB-290) is an investigational small molecule inhibitor of PARP1 and PARP2. According to OReO study(NCT03106987), the "PARPi after PARPi" strategy is effective in recurrent ovarian cancer patients previously treated with a PARP inhibitor. Therefore, we aim to further explore the use of PARP inhibitors in maintenance therapy for patients with ovarian cancer. Methods: This study (NCT05669768) will evaluate the efficacy and toxicity of pamiparib and tamoxifen in ovarian cancer patients with biochemical recurrence during first-line PARPi maintenance therapy. The included ovarian cancer patients are required to achieve No Evidence of Disease (NED) or demonstrated a response following platinum-based chemotherapy, with normalized CA-125 levels. First-line maintenance treatment with a PARP inhibitor is mandatory, with a minimum interval of ≥6 months to biochemical recurrence. The trial design is interventional, employing a Simon two-stage design to estimate sample size. The primary outcome of the study is the CA-125 response rate, which was assessed according to the GCIG criteria.1 The secondary outcome was Time to First Subsequent Therapy (TFST). Patients undergo regular assessments for tumor markers and imaging throughout treatment. If persistent elevation of tumor markers or the detection of recurrent lesions or distant metastases is observed, the patient is promptly removed from the study group. Standardized antitumor therapy is then initiated based on the patient's condition. The total planned enrollment is 46 participants, utilizing a single-group assignment and an open-label design. 1 of planned 12 patients for the first stage of accrual have been enrolled. Reference: 1. Rustin GJ, Vergote I, Eisenhauer E, et al. Definitions for response and progression in ovarian cancer clinical trials incorporating RECIST 1.1 and CA 125 agreed by the Gynecological Cancer Intergroup (GCIG). Int J Gynecol Cancer. 2011;21(2):419-423. Clinical trial information: NCT05669768 .

Use of Gynecologic Cancer Intergroup (GCIG) CA125 criteria to evaluate cell cycle checkpoint kinase 1 inhibitor (CHK1i) prexasertib response and disease progression (PD) in recurrent high-grade serous ovarian cancer (HGSOC).

e17536 Background: Data suggest discordance between serum biomarker CA125 and Response Evaluation Criteria in Solid Tumors (RECIST) response and/or PD in chemotherapies and PARP inhibitors. Here, we investigated the impact of CA125 on prognosis and its relationship with RECIST response/PD in HGSOC patients treated with a CHK1i, prexasertib. Methods: All relapsed HGSOC patients in this post-hoc analysis were treated with prexasertib at 105 mg/m2 IV every 14 days in a 28-day cycle until RECIST v1.1 PD, unacceptable toxicity, or consent withdrawal (NCT02203513). CA125 was assessed every cycle and CT scans obtained every two cycles. GCIG CA125 response was defined as &gt;50% reduction confirmed after 28 days and PD as &gt; 2X upper limit of normal (ULN) if baseline was normal or doubling of nadir if baseline was elevated. Patients with baseline CA125 &lt; 2X ULN or nadir &gt; 750 units/mL were not eligible for analysis. Clinical benefit rate (CBR; CR + PR + SD ≥ 6 months) was analyzed by Fisher’s exact test. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves and univariate (UV) and multivariate (MV) hazard ratios by Cox regression models. Positive predictive value (PPV) and negative predictive value (NPV) confidence intervals (CI) were estimated by the Wilson-Brown method. Results: Eighty-one patients received at least two cycles of prexasertib between January 2015 and November 2020, out of which 72 were evaluable by both RECIST and GCIG CA125 response criteria. CBR in the CA125 response (CA125-R) group (24/32; 75%) was significantly higher than the CA125 non-responder (CA125-N) group (12/40; 30%; p&lt;0.001). CA125 response tended to occur prior to RECIST response (median: 28 days; IQR: 28, 30). PFS was improved in CA125-R at 8.0 months vs. CA125-N at 3.5 months (UV HR: 0.34, 95% CI: 0.21-0.56; MV HR: 0.35, 95% CI: 0.20-0.59). OS was improved in CA125-R at 19.8 months vs. CA125-N at 10.3 months (HR: 0.43, 95% CI: 0.26-0.71; MV HR: 0.45, 95% CI: 0.27-0.75). No significant differences in PFS or OS were observed between subgroups by BRCA mutation status, platinum-sensitivity, FIGO stage, baseline CA125 value, or previous PARP inhibitor therapy in MV analysis. Out of 70 patients evaluable by RECIST and CA125 PD criteria, 43 patients had CA125 PD and 24 of those had RECIST PD occur within one cycle of CA125 PD (PPV: 59%; 95% CI: 43-72). Of the 27 patients without a CA125 PD, 9 patients also did not have a RECIST PD (NPV: 33%; 95% CI: 19-52). Conclusions: GCIG CA125 response is an independent predictor of response to CHK1i in HGSOC prior to the first restaging scans and is associated with a higher CBR and improved PFS and OS. However, GCIG CA125 PD has poor PPV and NPV within a one cycle window, indicating that CA125 alone is not sufficient in monitoring for PD in HGSOC treated with CHK1i.

Poor Concordance Between Cancer Antigen-125 and RECIST Assessment for Progression in Patients With Platinum-Sensitive Relapsed Ovarian Cancer on Maintenance Therapy With a Poly(ADP-ribose) Polymerase Inhibitor.

Cancer antigen-125 (CA-125) is recommended by treatment guidelines and widely used to diagnose ovarian cancer recurrence. The value of CA-125 as a surrogate for disease progression (PD) and its concordance with radiologic progression are unclear, particularly for women with platinum-sensitive relapsed ovarian cancer (PSROC) who have responded to chemotherapy and treated with maintenance poly(ADP-ribose) polymerase inhibitor (PARPi). In this pooled analysis of four randomized trials of maintenance PARPi or placebo (Study 19, SOLO2, ARIEL3, and NOVA), we extracted data on CA-125 PD as defined by Gynecologic Cancer InterGroup criteria and RECIST v1.1. We evaluated the concordance between CA-125 and RECIST PD and reported on the negative predictive value (NPV) and positive predictive value (PPV). Of 1,262 participants (n = 818 PARPi, n = 444 placebo), 403 (32%) had CA-125 PD, and of these, 366 had concordant RECIST PD (PPV, 91% [95% CI, 88 to 93]). However, of 859 (68%) without CA-125 PD, 382 also did not have RECIST PD (NPV, 44% [95% CI, 41 to 48]). Within the treatment arms, PPV remained high (PARPi, 91% [95% CI, 86 to 94]; placebo, 91% [95% CI, 86 to 95]) but NPV was lower on placebo (PARPi, 53% [95% CI, 49 to 57]; placebo, 25% [95% CI, 20 to 31]). Of 477 with RECIST-only PD, most (95%) had a normal CA-125 at the start of maintenance therapy and the majority (n = 304, 64%) had CA-125 that remained within normal range. Solid organ recurrence without peritoneal disease was more common in those with RECIST-only PD than in those with CA-125 and RECIST PD (36% v 24%; P < .001). In patients with PSROC treated with maintenance PARPi, almost half with RECIST PD did not have CA-125 PD, challenging current guidelines. Periodic computed tomography imaging should be considered as part of surveillance, particularly in those with a normal CA-125 at the start of maintenance therapy and on treatment.

Patient involvement in research within the Gynecological Cancer InterGroup: A call to action for a systematic approach: Results from a survey.

Involving patients in research, not only as trial subjects, is not a newly established practice. Over the last two decades, patient roles have gradually expanded to become active research contributors, creating a more patient-centered research landscape. Our survey has explored the scope of patient involvement within the Gynecologic Cancer InterGroup (GCIG), an International Gynecologic Cancer Research Consortium, and identified challenges in developing a systematic, meaningful and sustainable level of patient involvement. In late 2019, the GCIG Harmonisation Operations Committee conducted an online survey across 26 national and/or international research cooperative groups, aiming to identify current patient involvement practices implemented by each group. Twelve questions were asked. The results have been generated to support a systematic strategic planning process to increase patient involvement into clinical research projects. More than half of the 26 participating groups have either already involved (15, [58%]) or are planning (6, [23%]) to involve patients in their research activities. Gaining patient support in raising public awareness around clinical trials appears to be one of the most desired benefits (21, [81%]). Ten respondents managed to integrate patient involvement into their standard practice. When involving patients in research the groups mostly consider that patients bring added value to the study (19, [73%]), although only eight groups (40%) have a well-organized process in doing so. Even though patient involvement is considered a significant added value to clinical research, its application within GCIG groups is not considered on a regular basis and is predominantly limited to operational aspects of research activities. The lack of resources and expertize, as well as the missing well-organized and structured process of some groups, combined with their ability to ensure process sustainability, are among the main factors affecting implementation and adoption of patient involvement within GCIG research activities.

Prognostic value of CA125 kinetics, half-life, and nadir in the treatment of epithelial ovarian cancer: a systematic review and meta-analysis

ObjectiveTo investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers.MethodA comprehensive review of the Medline,...

Overcoming the challenges of drug development in platinum-resistant ovarian cancer.

The definition of "platinum-resistant ovarian cancer" has evolved; it now also reflects cancers for which platinum treatment is no longer an option. Standard of care for platinum-resistant ovarian cancer is single-agent, non-platinum chemotherapy with or without bevacizumab, which produces modest response rates, with the greatest benefits achieved using weekly paclitaxel. Several recent phase 3 trials of pretreated patients with prior bevacizumab exposure failed to meet their primary efficacy endpoints, highlighting the challenge in improving clinical outcomes among these patients. Combination treatment with antiangiogenics has improved outcomes, whereas combination strategies with immune checkpoint inhibitors have yielded modest results. Despite extensive translational research, there has been a lack of reliable and established biomarkers that predict treatment response in platinum-resistant ovarian cancer. Additionally, in the platinum-resistant setting, implications for the time between the penultimate dose of platinum therapy and platinum retreatment remain an area of debate. Addressing the unmet need for an effective treatment in the platinum-resistant setting requires thoughtful clinical trial design based on a growing understanding of the disease. Recent cancer drug approvals highlight the value of incorporating molecular phenotypes to better define patients who are more likely to respond to novel therapies. Clinical trials designed per the Gynecologic Cancer InterGroup recommendations-which advocate against relying solely upon the platinum-free interval-will help advance our understanding of recurrent ovarian cancer response where platinum rechallenge in the platinum-resistant setting may be considered. The inclusion of biomarkers in clinical trials will improve patient stratification and potentially demonstrate correlations with biomarker expression and duration of response. With the efficacy of antibody-drug conjugates shown for the treatment of some solid and hematologic cancers, current trials are evaluating the use of various novel conjugates in the setting of platinum-resistant ovarian cancer. Emerging novel treatments coupled with combination trials and biomarker explorations offer encouraging results for potential strategies to improve response rates and prolong progression-free survival in this population with high unmet need. This review outlines existing data from contemporary clinical trials of patients with platinum-resistant ovarian cancer and suggests historical synthetic benchmarks for non-randomized trials.

Survival and modelled cancer antigen-125 ELIMination rate constant K score in ovarian cancer patients in first-line before poly(ADP-ribose) polymerase inhibitor era: A Gynaecologic Cancer Intergroup meta-analysis

BackgroundIn patients with advanced ovarian cancer, the modelled CA-125 ELIMination rate constant K (KELIM) is an early indicator of the tumour intrinsic chemosensitivity. We assessed the prognostic and surrogate values of KELIM with respect to those of surgery outcome (based on post-operative residual lesions) in the Gynaecologic Cancer Intergroup (GCIG) individual patient data meta-analysis MAOV (Meta-Analysis in OVarian cancer) built before the emergence of poly(ADP-ribose) polymerase (PARP) inhibitors. MethodsThe dataset was split into learning and validation cohorts (ratio 1:2). The individual modelled KELIM values were estimated, standardised by the median value, then scored as unfavourable (<1.0) or favourable (≥1.0). Overall survival (OS) and progression-free survival (PFS) analyses were performed with a two-step meta-analytic approach and surrogacy through a two-level meta-analytic model. ResultsKELIM was assessed in 5884 patients from eight first-line trials (learning, 1962; validation, 3922). A favourable KELIM score was significantly associated with longer OS (validation set, median, 78.8 versus 28.4 months, hazard-ratios [HR] 0.46, 95% confidence interval [CI], 0.41–0.50, C-index 0.68), and longer PFS (validation set, median 30.5 versus 9.8 months, HR 0.49, 95% CI, 0.45–0.54, C-index 0.68), as were International Federation of Gynaecology and Obstetrics (FIGO) stage and debulking surgery outcome. Three prognostic groups were identified based on the surgery outcome and KELIM score, with large differences in OS (105.1, ∼45.0, and 22.1 months) and PFS (58.1, ∼15.0, and 8.0 months). Surrogacy for OS and for PFS was not established. ConclusionKELIM is an independent prognostic biomarker for survival, complementary to surgery outcome, representing a new determinant of first-line treatment success.

Development of a dual energy CT based model to assess response to treatment in patients with high grade serous ovarian cancer: a pilot cohort study

BackgroundIn patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC).MethodsSuitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes.Results62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43).ConclusionChanges in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC.Trial RegistrationCICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/.

An international randomized phase III trial comparing radical hysterectomy and pelvic node dissection (RH) vs simple hysterectomy and pelvic node dissection (SH) in patients with low-risk early-stage cervical cancer (LRESCC): A Gynecologic Cancer Intergroup study led by the Canadian Cancer Trials Group (CCTG CX.5-SHAPE).

LBA5511 Background: In the last 2 decades, there has been a trend towards less radical surgery in patients with low-risk cervical cancer. Retrospective data suggested that less radical surgery may be safe and associated with less morbidity. The objective of this non-inferiority phase III prospective randomized trial was to compare RH to SH in women with LRESCC. Methods: Women with LRESCC defined as stage 1A2 or 1B1 with lesion ≤ 2cm were randomized to RH or SH after stratification by cooperative group, intended use of sentinel node mapping, stage, histological type, and tumour grade. The primary endpoint was pelvic recurrence rate at 3 years (PRR3). Non-inferiority of SH to RH is claimed when the 95% upper one-sided confidence limit (95% UCL) for the difference in PRR3 of SH to RH (DPRR3), calculated by the Kaplan-Meier method for pelvic-relapse free survival, is lower than or equal to 4%. Primary intention to treat (ITT) analysis included all patients randomized. Per-protocol (PP) analysis included patients eligible at baseline and without evidence of more advanced disease found at the time of surgery or final pathology, based on treatment received. Secondary endpoints included extrapelvic relapse-free survival (ERFS), overall survival (OS), and quality of life (QoL). Results: 700 women (12 countries, 130 centers) were enrolled from December 2012 to November 2019. Patient characteristics were well balanced: median age was 44 (24-80); 91.7% were stage 1B1 and 61.7% had squamous histology. 50% of the hysterectomies were done laparoscopically (56% SH vs. 44% RH), 25% robotically (24% vs. 25%) and 23% abdominally (17% vs. 29%). 4.4% of patients had lymph node metastasis (4.1% SH and 5.1% RH) and 3.1% had extrauterine extension (2.6% SH and 3.7% RH). A total of 8.8% of women received post-surgical adjuvant therapy (9.2% SH and 8.4% RH). With a median follow-up of 4.5 years, 21 pelvic recurrences were identified (11 SH and 10 RH). The PRR3 was 2.5% with SH and 2.2% with RH (DPRR3 0.35% with 95% UCL 2.32%) in ITT analysis; 2.8% with SH and 2.3% with RH (DPRR3 0.42% with 95% UCL 2.56%) in PP analysis. The 3-year ERFS and OS were respectively 98.1% and 99.1% with SH; 99.7% and 99.4% with RH. RH had significantly higher surgery related incidence of urinary incontinence (11.0% vs. 4.7% with SH; p=0.003) and urinary retention (9.9% vs. 0.6% with SH; p&lt;0.0001) during follow-up. QoL scales with significant difference between the two groups over time were all in favor of SH. Conclusions: The pelvic recurrence rate at 3 years in women with low risk early-stage cervical cancer who underwent a simple hysterectomy is not inferior to those who received a radical hysterectomy. Fewer surgical complications and better quality of life were observed with SH. Clinical trial information: NCT01658930 .

CA-125 Early Dynamics to Predict Overall Survival in Women with Newly Diagnosed Advanced Ovarian Cancer Based on Meta-Analysis Data.

(1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients' monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy.

Efficacy and Safety of Weekly Paclitaxel Plus Vistusertib vs Paclitaxel Alone in Patients With Platinum-Resistant Ovarian High-Grade Serous Carcinoma

Patients with platinum-resistant or refractory ovarian high-grade serous carcinoma (PR-HGSC) have a poor prognosis and few therapeutic options. Preclinical studies support targeting PI3K/AKT/mTOR signaling in this setting, and a phase 1 study of the dual mTORC1/mTORC2 inhibitor vistusertib with weekly paclitaxel showed activity. To evaluate whether the addition of vistusertib to weekly paclitaxel improves clinical outcomes in patients with PR-HGSC. This phase 2, double-blind, placebo-controlled multicenter randomized clinical trial recruited patients from UK cancer centers between January 2016 and March 2018. Patients with PR-HGSC of ovarian, fallopian tube, or primary peritoneal origin and with measurable or evaluable disease (Response Evaluation Criteria in Solid Tumors version 1.1 and/or Gynecological Cancer Intergroup cancer antigen 125 criteria) were eligible. There were no restrictions on number of lines of prior therapy. Data analysis was performed from May 2019 to January 2022. Patients were randomized (1:1) to weekly paclitaxel (80 mg/m2 days 1, 8, and 15 of a 28-day cycle) plus oral vistusertib (50 mg twice daily) or placebo. The primary end point was progression-free survival in the intention-to-treat population. Secondary end points included response rate, overall survival, and quality of life. A total of 140 patients (median [range] age, 63 [36-86] years; 17.9% with platinum-refractory disease; 53.6% with ≥3 prior therapies) were randomized. In the paclitaxel plus vistusertib vs paclitaxel plus placebo groups, there was no difference in progression-free survival (median, 4.5 vs 4.1 months; hazard ratio [HR], 0.84; 80% CI, 0.67-1.07; 1-sided P = .18), overall survival (median, 9.7 vs 11.1 months; HR, 1.21; 80% CI, 0.91-1.60) or response rate (odds ratio, 0.86; 80% CI, 0.55-1.36). Grade 3 to 4 adverse events were 41.2% (weekly paclitaxel plus vistusertib) vs 36.7% (weekly paclitaxel plus placebo), and there was no difference in quality of life. In this randomized clinical trial of weekly paclitaxel and dual mTORC1/2 inhibition in patients with PR-HGSC, vistusertib did not improve clinical activity of weekly paclitaxel. isrctn.org Identifier: ISRCTN16426935.

Editorial introductions.

Editorial introductions.

Closing the gap for cervical cancer research in Vietnam: current perspectives and future opportunities: a report from the 5th Gynecologic Cancer InterGroup (GCIG) Cervical Cancer Research Network (CCRN) Education Symposium.

Closing the gap for cervical cancer research in Vietnam: current perspectives and future opportunities: a report from the 5th Gynecologic Cancer InterGroup (GCIG) Cervical Cancer Research Network (CCRN) Education Symposium.

Clinical research in ovarian cancer: consensus recommendations from the Gynecologic Cancer InterGroup.

The Gynecologic Cancer InterGroup (GCIG) sixth Ovarian Cancer Conference on Clinical Research was held virtually in October, 2021, following published consensus guidelines. The goal of the consensus meeting was to achieve harmonisation on the design elements of upcoming trials in ovarian cancer, to select important questions for future study, and to identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and adoption of 20 statements within four topic groups on clinical research in ovarian cancer including first line treatment, recurrent disease, disease subgroups, and future trials. Unanimous consensus was obtained for 14 of 20 statements, with greater than 90% concordance in the remaining six statements. The high acceptance rate following active deliberation among the GCIG groups confirmed that a consensus process could be applied in a virtual setting. Together with detailed categorisation of unmet needs, these consensus statements will promote the harmonisation of international clinical research in ovarian cancer.

Coordinated efforts to harmonise gynaecological cancer care.

Gynaecological cancers are among the most prevalent cancers in women worldwide. The types of cancers included in this group include cervical cancer, elimination of which has become a global goal in cancer control over the past two decades due to effective human papillomavirus (HPV) vaccination and screening programmes, and ovarian cancer, which still generally presents at a late stage due to a lack of effective screening tests and for which outcomes can be poor. In view of the prevalence of these cancers and the substantial burden these diseases have on women around the world, coordinated efforts are still very much needed to optimise treatment of women's cancers. In this issue of The Lancet Oncology, we publish a Series of two papers related to gynaecological cancers. In the first paper, Ignace Vergote and colleagues present the consensus recommendations from the sixth Gynecologic Cancer InterGroup (GCIG) Ovarian Cancer Consensus Conference on Clinical Research. In the second paper, Maria Kyrgiou and colleagues present the 2022 consensus recommendations on the terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer, in a concerted effort from the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology.

Mirvetuximab soravtansine (MIRV) in patients with platinum-resistant ovarian cancer with high folate receptor alpha (FRα) expression: Characterization of antitumor activity in the SORAYA study.

5512 Background: SORAYA is a global single arm phase 3 study evaluating MIRV in patients (pts) with FRα high platinum-resistant ovarian cancer (PROC). MIRV is an antibody drug conjugate comprising a FRα-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent. In this study, MIRV demonstrated activity in a broad population of PROC, regardless of number of prior lines of therapy or prior PARPi (Matulonis, SGO 2022). Here we describe details of response to treatment important for clinical decision making. Methods: SORAYA enrolled PROC pts with high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 75% of cells with PS2+ staining intensity) who had received 1-3 prior therapies, including required prior bevacizumab. Pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by investigator (INV) and the key secondary endpoint was duration of response (DOR); additional endpoints included time to response, CA-125 response, safety and tolerability. Results: 106 pts were enrolled; 51% had 3 prior lines; 48% had 1-2 prior lines of therapy; 48% received prior PARPi. ORR by INV was 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including five complete responses. Median time to response was 1.5 mos (range 1.0 to 5.6) and 71% of pts demonstrated tumor reduction. At the time of the protocol specified primary analysis (16 Nov 2021), the median DOR was 5.9 mos (95% CI: 5.6, 7.7). With 15 responders remaining on MIRV, the DOR continues to evolve. In the 86 response-evaluable patients for CA-125 (by Gynecologic Cancer Intergroup criteria), responses were observed in 46.5% (95% CI: 35.7, 57.6). Updated data will be presented including depth and duration of responses and impact of dose modifications. The most common treatment-related adverse events (TRAE; all grade, grade 3+) included blurred vision (41%, 6%), keratopathy (36%, 9%), and nausea (29%, 0%). TRAEs led to dose delays in 32%, dose reductions in 19%, and discontinuations in 7% of pts; one patient discontinued treatment due to an ocular event. The tolerability profile of MIRV consists of low-grade, reversible ocular and GI events, managed with dose modifications and supportive care. Conclusions: Treatment options for pts with PROC are limited. MIRV is the first biomarker-directed therapy demonstrating anti-tumor activity in pts with FRα high PROC. These results support the clinically meaningful impact MIRV has for pts with FRα high PROC, irrespective of prior therapies or dose modifications. Clinical trial information: NCT04209855.