Early integration of basic palliative care in cancer: scoping review of cross-sectorial models - components, facilitators, barriers.

BACKGROUND: Shared care between oncology specialists and general practice regarding the delivery of palliative care (PC) is necessary to meet the demands for a cohesive PC. The primary objective of this study is to investigate models of cross-sectorial integration between primary care and oncology specialists that have been developed to promote early and basic PC and factors influencing the process. METHOD: A scoping review was conducted using publications dated up until April 2023. Searches were conducted in MEDLINE, CINAHL, Embase, Web of Science and ProQuest Dissertations and Theses. Complementary searches were performed via reference lists and grey literature. Explicit early PC models aimed at patients with cancer aged ≥18 years with healthcare professionals from primary care and oncology constituted the inclusion criteria. The screening of the papers was performed independently by two reviewers. The reporting adheres to the extension for scoping reviews of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: The search provided 5630 articles of which six met the eligibility criteria, each describing a different model of early and cross-sectorial, integrated PC. 12 active components were identified. Education of staff as well as good communication and cooperation skills are essential factors to succeed with integrated, early PC. CONCLUSION: Integration of PC between general practice and oncology specialists has potential. The components of basic PC have been established. Factors known to influence the process are trust, communication and a common goal. Further research is required into strategies for approaching different levels of integration.

Through Clinicians Eyes: Use of an In-consultation Patient Decision Aid in Radiation Treatment for Early Breast Cancer. A Qualitative Study.

INTRODUCTION: Shared decision making (SDM) has become a crucial element on the political agenda and represents a vital aspect of modern healthcare. However, successful implementation of SDM highly depends on the attitude of clinicians towards SDM. The overall aim of our study was to explore the experience of oncologists and nurses with SDM using the Decision Helper, an in-consultation decision aid, at four Danish radiotherapy departments. METHODS: Semi-structured interviews were conducted with 20 clinicians. The participants were selected using purposive sampling to include nurses and oncologists, male and female, with different levels of experience with SDM and clinical work. The analysis was a data-driven, iterative process with inductive coding of all interviews and meaning condensation. RESULTS: Two main themes emerged: "Using the Decision Helper changes the consultation" and "Change of attitude among Danish oncologists." Each of the two themes included four elaborative subthemes, which are reported with supporting citations in this paper. In brief, the use of SDM and the Decision Helper should ideally be adjusted to the individual patient and depends highly on the oncologist. The participants described ambitions towards "making the right decision for this patient at this time." The healthcare system, however, has pitfalls that may hinder SDM, e.g., rigid interpretation of guideline-based recommendations. CONCLUSION: Using an in-consultation Decision Helper has the potential for individualized, structured patient engagement in decision making. There is a need for patient decision aids in clinical guidelines to ensure patient engagement in decision making.

Impact of timing and format of patient decision aids for breast cancer patients on their involvement in and preparedness for decision making - the IMPACTT randomised controlled trial protocol.

BACKGROUND: After curative surgery for early-stage breast cancer, patients face a decision on whether to undergo surgery alone or to receive one or more adjuvant treatments, which may lower the risk of recurrence. Variations in survival outcomes are often marginal but there are differences in the side effects and other features of the options that patients may value differently. Hence, the patient's values and preferences are critical in determining what option to choose. It is well-researched that the use of shared decision making and patient decision aids can support this choice in a discussion between patient and clinician. However, it is still to be investigated what impact the timing and format of the patient decision aid have on shared decision making outcomes. In this trial, we aim to investigate the impact of a digital pre-consult compared to a paper-based in-consult patient decision aid on patients' involvement in shared decision making, decisional conflict and preparedness to make a decision. METHODS: The study is a randomised controlled trial with 204 patients at two Danish oncology outpatient clinics. Eligible patients are newly diagnosed with early-stage breast cancer and offered adjuvant treatments after curative surgery to lower the risk of recurrence. Participants will be randomised to receive either an in-consult paper-based patient decision aid or a pre-consult digital patient decision aid. Data collection includes patient and clinician-reported outcomes as well as observer-reported shared decision making based on audio recordings of the consultation. The primary outcome is the extent to which patients are engaged in a shared decision making process reported by the patient. Secondary aims include the length of consultation, preparation for decision making, preferred role in shared decision making and decisional conflict. DISCUSSION: This study is the first known randomised, controlled trial comparing a digital, pre-consult patient decision aid to an identical paper-based, in-consult patient decision aid. It will contribute evidence on the impact of patient decision aids in terms of investigating if pre-consult digital patient decisions aids compared to in-consult paper-based decision aids support the cancer patients in being better prepared for decision making. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05573022).

Shared decision making with breast cancer patients - does it work? Results of the cluster-randomized, multicenter DBCG RT SDM trial.

BACKGROUND AND PURPOSE: Shared decision making (SDM) is a patient engaging process advocated especially for preference-sensitive decisions, such as adjuvant treatment after breast cancer. An increasing call for patient engagement in decision making highlights the need for a systematic SDM approach. The objective of this trial was to investigate whether the Decision Helper (DH), an in-consultation patient decision aid, increases patient engagement in decisions regarding adjuvant whole breast irradiation. MATERIAL AND METHODS: Oncologists at four radiotherapy units were randomized to practice SDM using the DH versus usual practice. Patient candidates for adjuvant whole breast irradiation after breast conserving surgery for node-negative breast cancer were eligible. The primary endpoint was patient-reported engagement in the decision process assessed with the Shared Decision Making Questionnaire (SDM-Q-9) (range 0-100, 4 points difference considered clinical relevant). Other endpoints included oncologist-reported patient engagement, decisional conflict, fear of cancer recurrence, and decision regret after 6 months. RESULTS: Of the 674 included patients, 635 (94.2%) completed the SDM-Q-9. Patients in the intervention group reported higher level of engagement (median 80; IQR 68.9 to 94.4) than the control group (71.1; IQR 55.6 to 82.2; p < 0.0001). Oncologist-reported patient engagement was higher in the invention group (93.3; IQR 82.2 to 100) compared to control group (73.3; IQR 60.0 to 84.4) (p < 0.0001). CONCLUSION: Patient engagement in medical decision making was significantly improved with the use of an in-consultation patient decision aid compared to standard. The DH on adjuvant whole breast irradiation is now recommended as standard of care in the Danish guideline.

Impact of an in-consult patient decision aid on treatment choices and outcomes of management for patients with an endoscopically resected malignant colorectal polyp: a study protocol for a non-randomised clinical phase II study.

INTRODUCTION: Management of an endoscopically resected malignant colorectal polyps can be challenging due to the risk of residual tumour and lymphatic spread. International studies have shown, that of those choosing surgical management instead of surveillance strategy, there are between 54% and 82% of bowel resections without evidence of residual tumour or lymphatic spread. As surgical management entails risks of complications and surveillance strategy entails risks of residual tumour or recurrence, a clinical dilemma arises when choosing a management strategy. Shared decision-making is a concept that can be used in preference-sensitive decision-making to facilitate patient involvement and empowerment to facilitate active patient participation in the decision-making process. METHODS AND ANALYSIS: This study protocol describes our clinical multi-institutional, non-randomised, interventional phase II study at Danish surgical departments planned to commence in the second quarter of 2024. The aim of this study is to examine whether shared decision-making and using a patient decision aid in consultations affect patients' choice of management, comparing with retrospective data. The secondary aim is to investigate patients' experiences, perceived involvement, satisfaction, decision conflict and other outcomes using questionnaire feedback directly from the patients. ETHICS AND DISSEMINATION: There are no conflicts of interest for principal or local investigators in any of the study sites. All results will be published at Danish and international meetings, and in English language scientific peer-reviewed journals. Our study underwent evaluation by the Regional Committees on Health Research Ethics for Southern Denmark (file number 20232000-47), concluding that formal approval was not required for this kind of research. TRIAL REGISTRATION NUMBER: NCT05776381.

Prognostic impact of early ctDNA dynamics during chemotherapy of metastatic cancer.

Aim: Clinical utility of the dynamics of ctDNA is sparse. This study aimed at evaluating the prognostic impact of early ctDNA dynamics in patients with metastatic cancer treated with chemotherapy. Materials & methods: The ctDNA dynamics were evaluated in 595 patients with metastatic cancer using droplet digital PCR. Results: Patients with an increase in ctDNA after one treatment cycle (n = 73; 12.2%) had an overall survival of 5.6 months compared with 8.6 months in patients with stable or decreasing ctDNA (n = 328; 55.1%) and 21.0 months in patients with undetectable ctDNA (p < 0.001; hazard ratio: 0.47; 95% CI: 0.41-0.53). Conclusion: Early ctDNA dynamics hold important prognostic information and have great implications for evaluation with the perspective of a more individualized treatment strategy.

Development, implementation and evaluation of patient decision aids supporting shared decision making in women with recurrent ovarian cancer.

Objective: Shared decision making (SDM) and use of patient decision aids (PtDAs) are key components in patient-centered care in relapsed ovarian cancer. This paper describes the development and implementation process of PtDAs into a clinical routine in three departments. Methods: Two PtDAs were developed in collaboration between patients and clinicians. Acceptability and usability of the PtDAs were tested on clinicians and patients using items from the internationally validated questionnaire "Preparation for Decision Making Scale". Results: Ten patients and 15 clinicians participated in the study. Most patients indicated that PtDAs would be helpful as preparation for the decision-making process with the clinicians. Ten (75%) of the clinicians responded that the PtDAs helped the patients to understand the benefits and disadvantages of each treatment option. Generally, the clinicians indicated that they would use SDM if they had a PtDA tailored to the clinical situation. Conclusions: Two PtDAs were systematically developed, tested, and implemented thereby supporting an SDM intervention. The PtDAs are still in use at the participating departments. Innovation: This study was successful in reusing a generic template for a patient decision aid (PtDA) developed at one institution and implemented in two other institutions. This was guided by a well-described systematic development process for PtDAs.

"SDM:HOSP"- a generic model for hospital-based implementation of shared decision making.

BACKGROUND: Shared decision making (SDM) is a core element in the meeting between patient and healthcare professionals, but has proved difficult to implement and sustain in routine clinical practice. One of five Danish regions set out to succeed and to develop a model that ensures lasting SDM based on learnings from large-scale real-world implementation initiatives that go beyond the 'barriers' and 'facilitators' research approach. This paper describes this process and development of a generic implementation model, SDM:HOSP. METHODS: This project was carried out in the Region of Southern Denmark with five major hospital units. Based on existing theory of SDM, SDM implementation, implementation science and improvement methodology, a process of four phases were described; development of conceptual elements, field-testing, evaluation, and development of the final implementation model. The conceptual elements developed aimed to prepare leaders, train SDM teachers, teach clinicians to perform SDM, support development of patient decision aids, and support systematic planning, execution and follow-up. Field testing was done including continuous participant evaluations and an overall evaluation after one year. RESULTS: Data from field testing and learnings from the implementation process, illustrated the need for a dynamic and easy adjustable model. The final SDM:HOSP model included four themes; i)Training of Leaders, ii) Training of Teachers and Clinicians, iii) Decision Helper, and iv) 'Process', each with details in three levels, 1) shared elements, 2) recommendations, and 3) local adaption. CONCLUSIONS: A feasible and acceptable model for implementation of SDM across hospitals and departments that accounts for different organizations and cultures was developed. The overall design can easily be adapted to other organizations and can be adjusted to fit the specific organization and culture. The results from the ongoing and overall evaluation suggest promising avenues for future work in further testing and research of the usability of the model.

Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer.

ABSTRACT: Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) exposed to paclitaxel. Serum NFL (sNFL) levels were quantified in 190 patients with ovarian cancer receiving paclitaxel/carboplatin chemotherapy at baseline and after each of the following 2 or 6 cycles. Adverse outcomes related to PIPN were retrospectively obtained, and Cox regression model was performed with different sNFL cut-offs after first cycle. The apparent elimination half-life of sNFL was estimated in patients who discontinued paclitaxel. Paclitaxel neurotoxicity in iPSC-SNs was accompanied by NFL release in a concentration-dependent manner ( P < 0.001, analysis of variance). Serum NFL levels increased substantially in patients during paclitaxel/carboplatin chemotherapy with considerable interindividual variability. Patients with sNFL >150 pg/mL after first cycle had increased risk to discontinue paclitaxel early (unadjusted HR: 2.47 [95% CI 1.16-5.22], adjusted HR: 2.25 [95% CI: 0.88-5.79]). Similar trends were shown for risk of severe PIPN and paclitaxel dose reduction because of PIPN. The median elimination half-life of sNFL was 43 days (IQR 27-82 days). Neurofilament light chain constitutes an objective biomarker of neurotoxicity in iPSC-SNs and in ovarian cancer patients with high sNFL predicting PIPN-related adverse outcomes. If prospectively validated, NFL can be used to study PIPN and may guide clinical decision making and personalize treatment with paclitaxel.

Single-cell and bulk RNA sequencing reveal ligands and receptors associated with worse overall survival in serous ovarian cancer.

BACKGROUND: Serous ovarian carcinoma is the most frequent histological subgroup of ovarian cancer and the leading cause of death among gynecologic tumors. The tumor microenvironment and cancer-associated fibroblasts (CAFs) have a critical role in the origin and progression of cancer. We comprehensively characterized the crosstalk between CAFs and ovarian cancer cells from malignant fluids to identify specific ligands and receptors mediating intercellular communications and disrupted pathways related to prognosis and therapy response. METHODS: Malignant fluids of serous ovarian cancer, including tumor-derived organoids, CAFs-enriched (eCAFs), and malignant effusion cells (no cultured) paired with normal ovarian tissues, were explored by RNA-sequencing. These data were integrated with single-cell RNA-sequencing data of ascites from ovarian cancer patients. The most relevant ligand and receptor interactions were used to identify differentially expressed genes with prognostic values in ovarian cancer. RESULTS: CAF ligands and epithelial cancer cell receptors were enriched for PI3K-AKT, focal adhesion, and epithelial-mesenchymal transition signaling pathways. Collagens, MIF, MDK, APP, and laminin were detected as the most significant signaling, and the top ligand-receptor interactions THBS2/THBS3 (CAFs)-CD47 (cancer cells), MDK (CAFs)-NCL/SDC2/SDC4 (cancer cells) as potential therapeutic targets. Interestingly, 34 genes encoding receptors and ligands of the PI3K pathway were associated with the outcome, response to treatment, and overall survival in ovarian cancer. Up-regulated genes from this list consistently predicted a worse overall survival (hazard ratio > 1.0 and log-rank P < 0.05) in two independent validation cohorts. CONCLUSIONS: This study describes critical signaling pathways, ligands, and receptors involved in the communication between CAFs and cancer cells that have prognostic and therapeutic significance in ovarian cancer. Video abstract.

Development of a Patient Decision Aid to Support Shared Decision Making for Patients with Recurrent High-Grade Glioma.

When high-grade gliomas recur, patients, their families, and clinicians face difficult medical decisions. There is no curable treatment, and the treatment options all come with a risk of complications and adverse effects. The patients are often cognitively affected, and they need tailored decision support. The objective of this study was to develop a patient decision aid (PtDA) targeted at patients with recurrent high-grade gliomas. Based on existing knowledge and the International Patient Decision Aids Standards, the PtDA was developed through an iterative process. The PtDA was alpha-tested by potential users to assess its acceptability and usability. The development team comprised three clinicians, two patients, two family members, and a researcher. The fifth version of the PtDA was submitted to the alpha test. Eleven patients, nine family members, and eleven clinicians assessed the PtDA and found it acceptable. Three changes were made during the alpha test. Most participants perceived the PtDA to prepare patients for decision making and improve consultations. The involvement of potential users was emphasized during the development and alpha test process. The PtDA was assessed as useful and acceptable by patients, family members, and clinicians in the decision-making situation of recurrent high-grade glioma.

Shared Decision Making with Acutely Hospitalized, Older Poly-Medicated Patients: A Mixed-Methods Study in an Emergency Department.

Shared decision making (SDM) about medicine with older poly-medicated patients is vital to improving adherence and preventing medication-related hospital admissions, but it is difficult to achieve in practice. This study's primary aim was to provide insight into the extent of SDM in medication decisions in the Emergency Department (ED) and to compare how it aligns with older poly-medicated patients' preferences and needs. We applied a mixed-methods design to investigate SDM in medication decisions from two perspectives: (1) observational measurements with the observing patient involvement (OPTION 5) instrument of healthcare professionals' SDM behavior in medication decisions and (2) semi-structured interviews with older poly-medicated patients. A convergent parallel analysis was performed. Sixty-five observations and fourteen interviews revealed four overall themes: (1) a low degree of SDM about medication, (2) a variation in the pro-active and non-active patients approach to conversations about medicine, (3) no information on side effects, and (4) a preference for medication reduction. The lack of SDM with older patients in the ED may increase inequality in health. Patients with low health literacy are at risk of safety threats, nonadherence, and preventable re-admissions. Therefore, healthcare professionals should systematically investigate older poly-medicated patients' preferences and discuss the side effects and the possibility of reducing harmful medicine.

The Long Non-Coding RNA SNHG12 as a Mediator of Carboplatin Resistance in Ovarian Cancer via Epigenetic Mechanisms.

Genetic and epigenetic changes contribute to intratumor heterogeneity and chemotherapy resistance in several tumor types. LncRNAs have been implicated, directly or indirectly, in the epigenetic regulation of gene expression. We investigated lncRNAs that potentially mediate carboplatin-resistance of cell subpopulations, influencing the progression of ovarian cancer (OC). Four carboplatin-sensitive OC cell lines (IGROV1, OVCAR3, OVCAR4, and OVCAR5), their derivative resistant cells, and two inherently carboplatin-resistant cell lines (OVCAR8 and Ovc316) were subjected to RNA sequencing and global DNA methylation analysis. Integrative and cross-validation analyses were performed using external (The Cancer Genome Atlas, TCGA dataset, n = 111 OC samples) and internal datasets (n = 39 OC samples) to identify lncRNA candidates. A total of 4255 differentially expressed genes (DEGs) and 14529 differentially methylated CpG positions (DMPs) were identified comparing sensitive and resistant OC cell lines. The comparison of DEGs between OC cell lines and TCGA-OC dataset revealed 570 genes, including 50 lncRNAs, associated with carboplatin resistance. Eleven lncRNAs showed DMPs, including the SNHG12. Knockdown of SNHG12 in Ovc316 and OVCAR8 cells increased their sensitivity to carboplatin. The results suggest that the lncRNA SNHG12 contributes to carboplatin resistance in OC and is a potential therapeutic target. We demonstrated that SNHG12 is functionally related to epigenetic mechanisms.

Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer.

Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making.

When life gives you no choice: Context of decision-making when offered an oncology clinical trial.

BACKGROUND: Patients with advanced cancer are faced with a wide variety of challenges and difficult treatment decisions made while in a vulnerable life-threatening situation, including decisions about clinical trial participation. Internationally, there is a great focus on shared decision-making as a way to help patients and healthcare professionals to make informed decisions together; nevertheless, research focusing on patient experiences shows that information about clinical trials is insufficient in supporting patients to make trial decisions in the context of their course of disease and managing life with advanced cancer. AIM: To explore where and how decisions about participation in oncology clinical trials are made and the role of the patients and healthcare professionals. METHODS: Participant observation was used as a qualitative research method to gain knowledge about decision-making in different clinical situations. Data were analysed using thematic analysis. RESULTS: Four themes were developed: (a) preformed decisions, (b) dissimilar perceptions of successful treatment, (c) cues and concerns stated by patients and (d) creating common ground. CONCLUSION: There are underexposed aspects to be aware of in the decision-making process for clinical trial participation. Preformed decisions made by the physicians before the encounter with patients seemed to narrow down the patients' options and could have benefited from including the patients' views. Cues and concerns stated by patients were often neglected. However, when physicians talked with the patients about truly difficult issues such as treatment expectations, hope and death, it led to another kind of conversation about treatment decisions involving the patients' preferences. IMPLICATIONS FOR PRACTICE: Awareness of preformed decisions and an increased focus on picking up cues and concerns about existential issues in the clinical encounter may improve the quality of the decisions and increase shared decision-making.

Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.

OBJECTIVE: In the Phase 3 VELIA trial (NCT02470585), veliparib added to carboplatin plus paclitaxel concomitantly and as maintenance for women with newly-diagnosed advanced ovarian cancer significantly improved progression-free survival (PFS) versus chemotherapy alone. Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status. METHODS: Women with untreated ovarian carcinoma were randomized (1:1:1) to: veliparib during chemotherapy and maintenance (veliparib-throughout), veliparib during chemotherapy followed by placebo maintenance (veliparib-combination only), or placebo during chemotherapy and maintenance (control). Chemotherapy included carboplatin plus dose-dense (DD; weekly) or every-3-week (Q3W) paclitaxel (a stratification factor at randomization), selected at the investigator's discretion pre-randomization. PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status. RESULTS: 1132 patients were analyzed by paclitaxel schedule. Pooled treatment arms demonstrated longer median PFS with DD (n = 586) versus Q3W (n = 546) paclitaxel (ITT: 20.5 vs 15.7 months, hazard ratio [HR] 0.77; homologous recombination proficient cancer: 15.1 vs 11.8 months, HR 0.64; BRCAwt: 18.0 vs 12.9 months, HR 0.70). Comparison between arms favored veliparib-throughout versus control in both DD (PFS, 24.2 vs 18.3 months, hazard ratio 0.67) and Q3W (19.3 vs 14.6, hazard ratio 0.69) subgroups. DD paclitaxel was associated with higher incidence of Grade 3/4 neutropenia, fatigue, and anemia versus Q3W. There were no differences in toxicity between gBRCAm (n = 211) and gBRCAwt (n = 902) subgroups. CONCLUSIONS: DD paclitaxel was tolerable and associated with longer PFS in the HR proficient and gBRCAwt groups, versus Q3W. gBRCA status did not impact safety.

Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.

OBJECTIVE: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy. METHODS: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks. RESULTS: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53-1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56-1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control. CONCLUSIONS: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials.