Results of a Phase Ib Study Investigating Durvalumab in Combination with Eribulin in Patients with HER2-Negative Metastatic Breast Cancer and Recurrent Ovarian Cancer.

INTRODUCTION: The release of tumor-associated antigens with cytotoxic chemotherapy treatment may enhance the response to immune checkpoint blockade. Eribulin is a microtubule inhibitor with proven overall survival (OS) benefit in metastatic breast cancer (MBC), which may also enhance intratumoral vascular remodeling. Durvalumab, a humanized monoclonal antibody, targets the programmed cell death ligand-1 (PD-L1) receptor. This study sought to determine the maximum tolerated dose and recommended phase II dose (RP2D) of eribulin in combination with durvalumab, as well as the safety and preliminary antitumor activity of the combination in patients with previously treated HER2-negative (HER2-) MBC and recurrent ovarian cancer (ROC). METHODS: Cohorts of 3-6 patients with HER2- MBC and ROC were treated in a modified 3+3 design. Eligible patients received escalating doses of eribulin (1.1 mg/m2 or 1.4 mg/m2 IV on day 1 and day 8) with durvalumab (1.12 g IV on day 1) in 21-day cycles until dose-limiting toxicity (DLT), intolerable adverse events (AEs), disease progression, or other reasons for withdrawal. PRIMARY ENDPOINT: the rate of DLTs during cycles 1 and 2 of therapy. Secondary endpoints: AE rate, objective response rate (ORR), progression-free survival (PFS), and OS. RESULTS: Nine patients with a median of 4 prior therapies for advanced disease were treated: 5 patients with HER2- MBC (1 with triple-negative disease and 4 with hormone-positive disease) and 4 patients with ROC. The RP2D of eribulin was 1.4 mg/m2 in combination with durvalumab. There were no DLTs experienced during the first two cycles of therapy. The most common treatment-related AEs (>50%) were fatigue, neutropenia, decreased white blood cell count, anemia, AST and alkaline phosphatase elevation, hyperglycemia, and nausea; most were grade 1 or 2. There was one immune-related AE of grade 3 (hepatitis) after 5 cycles of treatment, for which patient came off study. Two other patients discontinued study drug related to toxicity (neutropenia [n = 1], hepatic toxicity [n = 1]). ORR was 55%, and 4 additional patients experienced stable disease. All MBC patients exhibited a response to therapy. Median PFS was 6.2 months. Median OS was 15.0 months. CONCLUSION: The combination of eribulin at a dose of 1.4 mg/m2 with standard dose durvalumab had a favorable AE profile in patients with previously treated HER2- MBC and ROC. The early antitumor activity observed in all MBC patients enrolled in the study suggests that further investigation of this combination is warranted.

Secondary cytoreductive surgery and oncologic outcomes in the era of targeted maintenance therapy for recurrent, platinum-sensitive ovarian cancer.

OBJECTIVES: To compare oncologic outcomes of secondary cytoreductive surgery (SCS) before and after FDA approval of Poly(ADP-ribose) polymerase inhibitor (PARPi) and bevacizumab maintenance therapies for platinum-sensitive recurrent ovarian cancer (PS-ROC). METHODS: Patients who underwent SCS for first recurrence of PS-ROC from 1/1/2013-1/1/2020 were identified. Exclusion criteria included prior chemotherapy for recurrence, bowel obstruction procedures, and palliative surgery. Data were dichotomized pre/post 1/2017, relative to FDA approval of PARPi and bevacizumab maintenance for ROC. Second progression-free survival (PFS2), the primary endpoint, was estimated using Kaplan-Meier method. RESULTS: Overall, 245 patients underwent SCS-131 (53%) pre- and 114 (47%) post-approval. Most patients had high-grade serous tumors (83% and 90%, respectively; p = 0.13). Deleterious BRCA1/2 alterations were identified in 27% (32/120) and 28% (32/113) of tested patients, respectively (p = 0.88). Disease-free intervals pre- and post-approval were: 6-12 months, 16% and 18%; 12-30 months, 56% and 59%; and >30 months, 28% and 24%, respectively (p = 0.73). Overall, 85% and 86% of patients, respectively, achieved complete gross resection (CGR; p > 0.99). PARPi maintenance use increased from 3.8% to 27% (p < 0.001) following approval, and bevacizumab from 1.5% to 12% (p < 0.001). Median PFS2 was 19 and 20.1 months, respectively. In the post group, 1-year PFS2 rate was 84.5% (95% CI, 75.7-90.4%) for patients with CGR vs 56.2% (95% CI, 29.5-76.2%) for those with residual disease; 3-year PFS2 rates were 31.3% (95% CI, 21.6-41.4%) and 12.5% (95% CI, 2.1-32.8%), respectively (p = 0.001). CONCLUSIONS: CGR during SCS is associated with improved PFS2 compared to suboptimal resection. Prospective randomized trials are warranted to elucidate the role of SCS as more therapeutics become available.

TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer.

Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy.Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov).

Ongoing Phase II study randomizing vaccine OSE2101 +/- Pembrolizumab vs supportive care as maintenance in platinum-sensitive recurrent ovarian cancer.

Efficacy and safety of VEGFR inhibitors for recurrent ovarian cancer: a systematic review.

Aim: Vascular endothelial growth factor receptor inhibitors (VEGFRIs) have been common used for recurrent ovarian cancer (ROC), but insufficient high-level evidence on verifying its efficacy and safety. Methods: Randomized controlled trials (RCTs) were searched under eight electronic databases. Stata 14.0 and Review Manager 5.3 were used for data analysis. Certainty of the evidence was assessed using the GRADE profiler. This systematic review (SR) was registered under INPLASY (INPLASY202120019). Conclusion: Totally 23 RCTs involving 2810 patients were included in this SR. Current evidence revealed that VEGFRIs had better efficacy, survival and quality of life in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events (AEs), all the AEs could be manageable in the clinical practice.

The expression of VEGF/VEGF receptors (VEGFRs) in ovarian cancer (OC) tissue was found to be higher than in benign or normal ovarian tissue. Therefore angiogenesis inhibitors play an essential role in OC treatment. Many anti-angiogenic agents have been developed in recent years. The role of small-molecule inhibitors of VEGFRs for recurrent OC (ROC) has demonstrated significant antitumor efficacy. These drugs include Nintedanib, Axitinib, Pazopanib, Sorafenib, Vandetanib, Sunitinib, Cediranib, Ramucirumab and Apatinib, and more are in the way. However, insufficient high-level evidence from systematic reviews (SRs) focused on VEGFRIs for ROC. Therefore, we performed an SR to investigate the efficacy and safety of VEGFRIs for patients with ROC. This SR was registered under INPLASY (INPLASY202120019). Totally 23 RCTs involving 2810 patients were included in this SR. The results indicate that VEGFRIs have better efficacy and survival in the treatment of ROC. Though VEGFRIs increase some drug-related adverse events, all the adverse events could be manageable in clinical practice.

Efficacy and safety of niraparib in platinum-sensitive recurrent ovarian cancer: retrospective observational study in a tertiary hospital.

BACKGROUND: Niraparib has been authorized for maintenance treatment of epithelial ovarian cancer after first-line treatment with platinum, in partial or complete response. OBJECTIVES: To evaluate the effectiveness and safety of maintenance niraparib in platinum-sensitive recurrent ovarian cancer (PSROC) patients in a tertiary hospital. MATERIALS AND METHODS: This retrospective observational unicentre study included women diagnosed with ovarian adenocarcinoma who received niraparib. Eligibility criteria encompassed women with PSROC, in response to platinum chemotherapy, and not previously treated with other PARPis. Data on demographics, comorbidities, BRCA mutation status, disease stage, treatment history and adverse events were recorded. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. RESULTS: A total of 33 patients were included, with a median age of 63.5 years. The majority of patients received niraparib at 200 mg/day based on Research on Adverse Drug Events and Report criteria. Median OS was 30 months (95% CI: 16.76-43.23), and median PFS was 8 months (95% CI: 2.48-13.52). Adverse effects were more frequent during the initial months of treatment, with most classified as CTCAE v5 grade 1-2. Dose reductions, interruption of treatment and discontinuations were observed due to haematologic toxicities primarily. CONCLUSION: This real-world study showed that maintenance niraparib in PSROC patients had effectiveness and safety profiles consistent with clinical trials and other observational studies. Median PFS and OS were comparable to previous reports, and most adverse events were manageable with dose modifications. The results support the use of niraparib as a maintenance therapy option in this patient population.

Efficacy and safety of oxaliplatin-based hyperthermic intraperitoneal chemotherapy with secondary cytoreduction for platinum resistant recurrent ovarian cancer: A single-center retrospective cohort study.

BACKGROUND/PURPOSE: This retrospective study evaluated the efficacy and adverse effects of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) with secondary cytoreductive surgery (CRS) in patients with recurrent ovarian cancer. METHODS: Patients diagnosed with recurrent epithelial ovarian cancer, including fallopian tube and peritoneal origin, who underwent oxaliplatin-based HIPEC with secondary CRS, were enrolled. The primary outcome was progression-free survival (PFS), and the secondary outcomes were overall survival (OS) and adverse events. RESULTS: A total of 33 patients were included in the analysis. The mean PFS and OS were 20.4 months (95% CI 16.3-24.5 months) and 26.7 months (95% CI 23.7-29.7), respectively. Furthermore, the OS and PFS between platinum-sensitive and resistant recurrence showed no significant difference. Univariate and multivariate analysis of PFS identified a pre-operative peritoneal carcinomatosis index (PCI) score of ≥5 as a poor prognostic factor. Among them, the incidence of acute kidney injury was 9.0 % & none had grade ≧3 adverse events. CONCLUSION: Oxaliplatin-based HIPEC with secondary CRS might provide a survival benefit for patients with recurrent ovarian cancer with a decreased incidence of renal toxicity compared to cisplatin-based regimens. It might be effective and feasible in selected recurrent ovarian cancer patients, regardless of platinum-sensitive or resistant.

Randomized, two-arm, noncomparative phase 2 study of olaparib plus cediranib or durvalumab in HRR-mutated, platinum-resistant ovarian cancer: A substudy of KGOG 3045.

Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.

The 2022 PSOGI International Consensus on HIPEC Regimens for Peritoneal Malignancies: Epithelial Ovarian Cancer.

BACKGROUND AND AIM: We report the results of an international consensus on hyperthermic intraperitoneal chemotherapy (HIPEC) regimens for epithelial ovarian cancer (EOC) performed with the following goals: To define the indications for HIPEC To identify the most suitable HIPEC regimens for each indication in EOC To identify areas of future research on HIPEC To provide recommendations for some aspects of perioperative care for HIPEC METHODS: The Delphi technique was used with two rounds of voting. There were three categories of questions: evidence-based recommendations [using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system with the patient, intervention, comparator, and outcome (PICO) method], an opinion survey, and research recommendations. RESULTS: Seventy-three (67.5%) of 108 invited experts responded in round I, and 68 (62.9%) in round II. Consensus was achieved for 34/38 (94.7%) questions. However, a strong positive consensus that would lead to inclusion in routine care was reached for only 6/38 (15.7%) questions. HIPEC in addition to interval cytoreductive surgery (CRS) received a strong positive recommendation that merits inclusion in routine care. Single-agent cisplatin was the only drug recommended for routine care, and OVHIPEC-1 was the most preferred regimen. The panel recommended performing HIPEC for a minimum of 60 min with a recommended minimum intraabdominal temperature of 41°C. Nephroprotection with sodium thiosulfate should be used for cisplatin HIPEC. CONCLUSIONS: The results of this consensus should guide clinical decisions on indications of HIPEC and the choice and various parameters of HIPEC regimens and could fill current knowledge gaps. These outcomes should be the basis for designing future clinical trials on HIPEC in EOC.

Study protocol for prospective multi-institutional phase III trial of standard of care therapy with or without stereotactic ablative radiation therapy for recurrent ovarian cancer (SABR-ROC).

BACKGROUND: Efforts have been made to investigate the role of salvage radiotherapy (RT) in treating recurrent ovarian cancer (ROC). Stereotactic ablative radiation therapy (SABR) is a state-of-the-art therapy that uses intensity modulation to increase the fractional dose, decrease the number of fractions, and target tumors with high precision. METHODS: The SABR-ROC trial is a phase 3, multicenter, randomized, prospective study to evaluate whether the addition of SABR to the standard of care significantly improves the 3-year overall survival (OS) of patients with ROC. Patients who have completed the standard treatment for primary epithelial ovarian cancer are eligible. In addition, patients with number of metastases ≤ 10 and maximum diameter of each metastatic site of gross tumor ≤ 5 cm are allowed. Randomization will be stratified by (1) No. of the following clinical factors met, platinum sensitivity, absence of ascites, normal level of CA125, and ECOG performance status of 0-1; 0-3 vs. 4; (2) site of recurrence; with vs. without lymph nodes; and (3) PARP inhibitor; use vs. non-use. The target number of patients to be enrolled in this study is 270. Participants will be randomized in a 1:2 ratio. Participants in Arm 2 will receive SABR for recurrent lesions clearly identified in imaging tests as well as the standard of care (Arm 1) based on treatment guidelines and decisions made in multidisciplinary discussions. The RT fraction number can range from 1 to 10, and the accepted dose range is 16-45 Gy. The RT Quality Assurance (QA) program consists of a three-tiered system: general credentialing, trial-specific credentialing, and individual case reviews. DISCUSSION: SABR appears to be preferable as it does not interfere with the schedule of systemic treatment by minimizing the elapsed days of RT. The synergistic effect between systemic treatment and SABR is expected to reduce the tumor burden by eradicating gross tumors identified through imaging with SABR and controlling microscopic cancer with systemic treatment. It might also be beneficial for quality-of-life preservation in older adults or heavily treated patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT05444270) on June 29th, 2022.

Outcomes and long-term follow-up by treatment type for patients with advanced-stage ovarian cancer managed at a tertiary cancer center: A Memorial Sloan Kettering Cancer Center Team Ovary study.

OBJECTIVE: To assess long-term outcomes of patients with advanced-stage ovarian cancer by treatment type. METHODS: Patients with newly diagnosed stage III-IV ovarian cancer who underwent primary treatment at our tertiary cancer center from 01/01/2015-12/31/2015 were included. We reviewed electronic medical records for clinicopathological, treatment, and survival characteristics. RESULTS: Of 153 patients, 88 (58%) had stage III and 65 (42%) stage IV disease. Median follow-up was 65.8 months (range, 3.6-75.3). Eighty-nine patients (58%) underwent primary debulking surgery (PDS), 50 (33%) received neoadjuvant chemotherapy followed by interval debulking surgery (IDS), and 14 (9%) received chemotherapy alone, without surgery (NSx). Median PFS to first recurrence was 26.2 months (range, 20.1-36.2), 13.5 months (range, 12-15.1), and 4.2 months (range, 1.1-5.8) in the PDS, IDS, and NSx groups, respectively (P < .001). At first recurrence/progression, 80 patients (72.7%) were treated with chemotherapy, 28 (25.5%) underwent secondary cytoreductive surgery (CRS) followed by chemotherapy, and 2 (1.8%) received no treatment. Seven patients (4.6%) underwent palliative surgery for malignant bowel obstruction. Overall, 62.7% received 1-3 lines of chemotherapy. The 5-year OS rates were 53.2% (95% CI: 44.7%-61%) for the entire cohort, 71.5% (95% CI: 60.2%-80%) for the PDS group, 35.2% (95% CI: 22.2-48.5%) for the IDS group, and 7.9% (95% CI: 0.5%-29.9%) for the NSx group. CONCLUSION: The longitudinal treatment modalities and outcomes of patients with advanced ovarian cancer described here can be useful for patient counseling, long-term planning, and future comparison studies.

Morbidity after secondary cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy for ovarian cancer: An analysis of a randomized phase II trial.

OBJECTIVE: To assess postoperative complications after secondary cytoreductive surgery (SCS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC), we conducted an exploratory analysis of patients with platinum-sensitive recurrent ovarian cancer enrolled in a randomized phase II trial. METHODS: Complications occurring within 30 days of surgery were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0; only hemoglobin and platelet levels were assessed. Patients were grouped by CTCAE grade ≥ 3 and < 3 complications. RESULTS: Among 83 eligible patients, 33 (40%) had grade ≥ 3 complications and 50 (60%) had grade < 3 complications; anemia and abdominal infections were the most common. There were no perioperative mortalities. Time to initiation of postoperative chemotherapy for patients with grade ≥ 3 and grade < 3 events was 34 days (range, 18-60) and 31 days (range, 21-43), respectively (P = .017). Median progression-free survival (PFS) did not significantly differ between patients with grade ≥ 3 and grade < 3 complications (11.2 months [95% CI: 9.3-14.4] vs 14.9 months [95% CI: 11.3-16.5], respectively; P = .186), nor did median overall survival (OS) (46.9 months [95% CI: 34-NE] vs 68.2 months [95% CI: 52.1-NE], respectively; P = .053). CONCLUSION: Postoperative complications following SCS with or without HIPEC were associated with slight delays in chemotherapy initiation but did not significantly impact oncologic outcomes.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

Hyperthermic intraperitoneal chemotherapy in the treatment of recurrent ovarian cancer: When, and for whom?

OBJECTIVE: The aim of this study is to evaluate the progression-free survival (PFS) of recurrent ovarian cancer (ROC) patients treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC). MATERIALS AND METHODS: ROC patients who underwent cytoreductive surgery plus HIPEC between 2015 and 2021 were retrospectively evaluated. Patients' demographic information and clinicopathological characteristics including cancer type, histology, platinum status, presence of ascites, type of surgery, complications, chemotherapy history, and disease progression were documented. PFS was calculated using the Kaplan-Meier method. RESULTS: A total of 104 patients with ROC were included. The median age was 57 years and the median follow-up time was 15 months (range: 5-69 months). In Cox regression multivariate analyses, platinum resistance (hazard ratio [HR]: 3.32, 95% confidence interval [CI]: 1.91-5.76, p = 0.00), more than one relapse prior HIPEC (HR: 2.81, 95% CI: 1.65-4.87, p = 0.024), and presence of ascites (HR: 1.88, 95% CI: 1.08-3.26, p = 0.00) were found to be negative prognostic factors for PFS. In subgroup analyses of patients with the first recurrence, the median PFS was 21 months for platinum-sensitive patients and 6 months for platinum-resistant patients (p = 0.032). CONCLUSION: HIPEC at the time of first platinum-sensitive relapse may lead to favorable PFS in the treatment ROC. However, HIPEC as salvage treatment even with R0 cytoreductive surgery does not seem effective.

The role of surgery in platinum-resistant ovarian cancer: A call to the scientific community.

In the last decade, a growing attention has been focused on identifying effective therapeutic strategies also in the orphan clinical setting of women with platinum-resistant disease. In this context, secondary cytoreductive surgery (SCS) remains a potential approach only in women with platinum sensitive relapse, but experimental data have been published supporting the role of SCS also in patients with platinum-resistant recurrence. In particular, surgery is emerging as a potential option in specific subgroups of women, such as those patients with low-grade serous histology, or low-volume relapse with disease located in the so-called pharmacological sanctuaries. Furthermore, contrasting evidences have suggested a potential role in this clinical setting of SCS combined with intraperitoneal hyperthermic chemotherapy. In this complex scenario we review here the available evidences regarding the role surgery in ovarian cancer patients with platinum resistant disease, trying also to understand which patients may benefit from this challenging, experimental approach.

Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.

BACKGROUND: Rucaparib is a poly(ADP-ribose) polymerase inhibitor approved in Europe as maintenance therapy for recurrent platinum-sensitive (Pt-S) ovarian cancer (OC). The Rucaparib Access Programme (RAP) was designed to provide early access to rucaparib for the above-mentioned indication, as well as for patients with BRCA-mutated Pt-S or platinum-resistant (Pt-R) OC and no therapeutic alternatives. METHODS: In this observational, retrospective study we analysed the efficacy and safety of rucaparib within the RAP in Spain. Hospitals associated with the Spanish Ovarian Cancer Research Group (GEICO) recruited patients with high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer treated with rucaparib 600 mg twice daily as maintenance or treatment (Pt-S/Pt-R) in the RAP. Baseline characteristics, efficacy, and safety data were collected. RESULTS: Between July 2020 and February 2021, 51 patients treated in 22 hospitals in the RAP were included in the study. Eighteen patients with a median of 3 (range, 1-6) prior treatment lines received rucaparib as maintenance; median progression-free survival (PFS) for this group was 9.1 months (95% confidence interval [CI], 4.2-11.6 months). Among 33 patients (median 5 [range, 1-9] prior treatment lines) who received rucaparib as treatment, 7 and 26 patients had Pt-S and Pt-R disease, respectively. Median PFS was 10.6 months (95% CI, 2.5 months-not reached) in the Pt-S group and 2.2 months (95% CI, 1.1-3.2 months) in the Pt-R group. Grade ≥ 3 treatment-emergent adverse events were reported in 39% of all patients, the most common being anaemia (12% and 15% in the maintenance and treatment groups, respectively). At data cut-off, 5 patients remained on treatment. CONCLUSION: Efficacy results in these heavily pre-treated patients were similar to those from previous trials. The safety profile of rucaparib in real life was predictable and manageable.

Phase II study of enzalutamide in androgen receptor positive, recurrent, high- and low-grade serous ovarian cancer.

OBJECTIVES: We sought to determine the safety and efficacy of the oral androgen receptor antagonist enzalutamide in patients with previously treated, recurrent, AR-positive (AR+) ovarian cancer. METHODS: This was a single-institution phase II study of patients with AR+ ovarian cancer with measurable disease with 1-3 prior lines of chemotherapy; patients were screened for enrollment from 11/2013-7/2018. Following consent, archival tissue was evaluated for AR+. Enrolled patients received daily enzalutamide 160 mg until progression of disease or treatment discontinuation. Adverse events were graded by CTCAE v4.0. Co-primary endpoints were 6-month progression-free survival (PFS6) and overall response rate (ORR) by RECIST 1.1 criteria. RESULTS: During the study period, 160 patients were screened and 59 (45 high-grade serous [HGS] and 14 low-grade serous [LGS]) consented to treatment on study. There was 1 confirmed and 1 unconfirmed partial response. The ORR was 1.7% (90% CI: 0.2-100%). The overall PFS6 rate (as binary) was 22% (90% CI: 15.1-100%). The 6-month PFS rate (as time to event) was 19.8% for HGS patients (90% CI: 12.7-100%) and 38.5% (90% CI: 21.7%-100%) for LGS patients. Grade 3 toxicities occurred in 6 patients (one toxicity (Grade 3 rash) was considered a dose-limiting toxicity). One patient died of cardiac arrest after 42 days on treatment of a cardiac arrest not attributed to study drug. CONCLUSIONS: The study met its primary endpoint, with a PFS6 rate of 22% (n = 13); however, the overall response rate was low. Enzalutamide was well tolerated and may be a potential treatment option in select patients.

Paclitaxel with or without pazopanib for ovarian cancer relapsing during bevacizumab maintenance therapy: The GINECO randomized phase II TAPAZ study.

BACKGROUND: Anti-angiogenic rechallenge with bevacizumab plus chemotherapy is effective in recurrent ovarian cancer (rOC); however, data are limited on tyrosine kinase inhibitors after progression on maintenance bevacizumab. METHODS: In the randomized phase II TAPAZ trial, patients with rOC during the first year of bevacizumab maintenance therapy were assigned 2:1 to either weekly paclitaxel 65 mg/m2 plus pazopanib 600-800 mg daily or standard weekly paclitaxel 80 mg/m2. The primary endpoint was 4-month progression-free survival (PFS) rate. RESULTS: Overall, 116 patients were randomized and treated: 79 with combination therapy and 37 with single-agent paclitaxel. Median follow-up was 13.1 months. There was no difference between treatment arms in 4-month PFS rate (61% [95% CI, 51-73%] with the combination versus 68% [95% CI, 54-85%] with paclitaxel alone), median PFS (4.9 [95% CI, 4.1-6.1] versus 5.8 [95% CI, 4.8-7.4] months, respectively) or median overall survival (13.6 versus 12.9 months, respectively). The combination was associated with more grade 3/4 toxicities (87% versus 70%, respectively) and toxicity-related paclitaxel discontinuations (22% versus 11%). Pazopanib was discontinued for toxicity in 44% of patients, most commonly for gastrointestinal and vascular events. There were two treatment-related deaths, both in the combination arm (pulmonary embolism and gastrointestinal perforation). At month 4, patient-reported outcomes deteriorated from baseline in the combination arm, particularly for abdominal/gastrointestinal symptoms, which showed a clinically important difference versus paclitaxel alone. CONCLUSIONS: In rOC progressing during maintenance bevacizumab, adding pazopanib to paclitaxel did not improve efficacy, increased toxicity, and compromised chemotherapy delivery. CLINICALTRIALS: govregistration:NCT02383251.

Measure of Ovarian Symptoms and Treatment concerns (MOST) indexes and their associations with health-related quality of life in recurrent ovarian cancer.

PURPOSE: The Measure of Ovarian Symptoms and Treatment (MOST) concerns is a validated patient-reported symptom assessment tool for assessing symptom benefit and adverse effects of palliative chemotherapy in women with recurrent ovarian cancer (ROC). We aimed to examine (i) how symptoms within MOST symptom indexes track together (i.e. co-occur) and (ii) the association between MOST symptom indexes and key aspects of health-related quality of life (HRQL). METHOD: A prospective cohort of women with ROC completed the MOST-T35, EORTC QLQ-C30 and EORTC QLQ-OV28 at baseline and before each cycle of chemotherapy. Analyses were conducted on baseline and end-of-treatment data. Exploratory factor analysis and hierarchical cluster analysis identified groups of co-occurring symptoms. Path models examined associations between MOST symptom indexes and HRQL. RESULTS: Data from 762 women at baseline and 681 at treatment-end who completed all 22 symptom-specific MOST items and at least one HRQL measure were analysed. Four symptom clusters emerged at baseline and treatment-end: abdominal symptoms, symptoms associated with peripheral neuropathy, nausea and vomiting, and psychological symptoms. Psychological symptoms (MOST-Psych) and symptoms due to disease (ovarian cancer) or treatment (MOST-DorT) were associated with poorer scores on QLQ-C30 and OV28 functioning domains and worse overall health at both time points. CONCLUSION: Four MOST symptom clusters were consistent across statistical methods and time points. These findings suggest that routine standardized assessment of psychological and physical symptoms in clinical practice with MOST plus appropriate symptom management referral pathways is an intervention for improving HRQL that warrants further research.

Who are the long-term survivors of recurrent ovarian carcinoma?: a retrospective analysis of a multicenter study.

BACKGROUND: The aim of the present study was to investigate the incidence and hallmarks of long-term survivors of recurrent ovarian carcinoma (LTSROC) in a large-scale retrospective cohort of patients from a multicenter study group. METHODS: We performed a regional multicenter retrospective study between January 1986 and September 2021 using clinical data collected under the central pathological review system. Patients who underwent surgery for primary OC at diagnosis and developed recurrent tumors after the initial treatment were included. We defined LTSROC as patients who survived for 5 years or longer after initial tumor recurrence and examined factors affecting the long-term survival of ROC and outcomes of LTSROC. RESULTS: We collected information on patients with malignant ovarian tumors and finally 657 of them that developed ROC were included in the study population. Sixty-eight (10.4%) patients were LTSROC while 399 (60.7%) were short-term survivors of recurrent ovarian carcinoma. In a multivariate logistic regression analysis, negative ascites cytology [odds ratio (OR) 1.865; 95% CI 1.026-3.393; p = 0.041] and a recurrence-free interval (RFI) of 1 year or longer (OR 2.896; 95% CI 1.546-5.425; p < 0.001) were identified as independent factors associated with LTSROC. Approximately 80% of LTSROC presented with solitary recurrent tumors. Furthermore, more than 50% of LTSROC underwent tumor debulking surgery for the first recurrent tumor with or without chemotherapy. CONCLUSION: RFI of 1 year or longer and negative ascites cytology in the initial surgery were identified as independent predictive factors for LTSROC.

Apatinib plus paclitaxel versus paclitaxel monotherapy for platinum-resistant recurrent ovarian cancer treatment: A retrospective cohort study.

WHAT IS KNOWN AND OBJECTIVE: Apatinib, an oral antiangiogenic drug, exerts potential anti-tumour effects on platinum-resistant recurrent ovarian cancer (PROC). This study intended to evaluate the efficacy and safety of apatinib plus paclitaxel compared to paclitaxel monotherapy in PROC patients. METHODS: This retrospective cohort study reviewed 70 PROC patients who received apatinib plus paclitaxel (apatinib plus paclitaxel group) (N = 32) or paclitaxel monotherapy (paclitaxel monotherapy group) (N = 38). The recommended regimens were as follows: paclitaxel (60 mg/m2 ) administrated once a week with a maximum of 18 weeks; apatinib (250-375 mg/day) administrated until disease progression or patient intolerance. RESULTS AND DISCUSSION: Disease control rate was elevated (84.4% vs. 60.5%, P = 0.028), whereas objective response rate only disclosed an increasing trend (lacked statistical significance) (37.5% vs. 18.4%, P = 0.074) in apatinib plus paclitaxel group compared with paclitaxel monotherapy group. Progression-free survival (median [95% confidence interval (CI)]: 5.0 [2.5-7.5] months vs. 3.8 [2.4-5.2] months, P = 0.033) and overall survival (median [95% CI]: 21.1 [13.2-29.0] months vs. 14.8 [11.4-18.2] months, P = 0.032) were both prolonged in apatinib plus paclitaxel group compared to paclitaxel monotherapy group, which were further verified in the multivariate Cox's proportional hazard regression analyses (both P < 0.050). Additionally, the incidence of each adverse event was not different between the two groups (all P > 0.050). WHAT IS NEW AND CONCLUSION: Apatinib plus paclitaxel exhibits better efficacy and acceptable toxicity compared with paclitaxel monotherapy in PROC patients.