"Having cancer is very expensive": A qualitative study of patients with ovarian cancer and PARP inhibitor treatment.

OBJECTIVE: To examine patient barriers and facilitators to PARP inhibitor (PARP-I) maintenance therapy in ovarian cancer. PARP-I improves survival in ovarian cancer, but these multi-year therapies cost around $100,000 annually and are under-prescribed. METHODS: We recruited patients with ovarian cancer treated with PARP-I maintenance therapy at an academic health system for a semi-structured interview. Patient demographics, including genetics and PARP-I cost, were self-reported. We assessed patient experiences with barriers and facilitators of PARP-I usage. Two team members used a thematic approach to analyze and identify key themes. RESULTS: In May 2022, we interviewed 10 patients (mean age = 65 years; 80% White; 60% with a germline genetic mutation). Patients paid on average $227.50 monthly for PARP-I, straining resources for some participants. While sampled patients were insured, all patients identified having no or inadequate insurance as a major barrier to PARP-I. At the same time, all participants prioritized clinical effectiveness over costs of care. Patients identified PARP-I delivery from specialty pharmacies, separate and different from other medications, as a potential barrier, but each had been able to navigate delivery. Patients expressed significant initial side effects of PARP-I as a potential barrier yet reported clinician communication and prompt dose reduction as facilitating continuation. CONCLUSIONS: Patients identified cost, restrictive pharmacy benefits, and initial side effects as barriers to PARP-I usage. Having insurance and a supportive care team were identified as facilitators. Enhancing communication about PARP-I cost and side effects could improve patient experience and receipt of evidence-based maintenance therapy in ovarian cancer.

Unmet financial needs among patients crowdfunding to support gynecologic cancer care.

BACKGROUND: Patients may use crowdfunding to solicit donations, typically from multiple small donors using internet-based means, to offset the financial toxicity of cancer care. OBJECTIVE: To describe crowdfunding campaigns by gynecologic cancer patients and to compare campaign characteristics and needs expressed between patients with cervical, uterine, and ovarian cancer. STUDY DESIGN: We queried the public crowdfunding forum GoFundMe.com for "cervical cancer," "uterine cancer," and "ovarian cancer." The first 200 consecutive posts for each cancer type fundraising within the United States were analyzed. Data on campaign goals and needs expressed were manually extracted. Descriptive statistics and bivariate analyses were performed. RESULTS: Among the 600 fundraising pages, the median campaign goal was $10,000 [IQR $5000-$23,000]. Campaigns raised a median of 28.6% of their goal with only 8.7% of campaigns reaching their goal after a median of 54 days online. On average, ovarian cancer campaigns had higher monetary goals, more donors, and larger donation amounts than cervical cancer campaigns and raised more money than both cervical and uterine cancer campaigns. Campaigns were fundraising to support medical costs (80-85%) followed by lost wages (36-56%) or living expenses (27-41%). Cervical cancer campaigns reported need for non-medical costs more frequently than uterine or ovarian cancer campaigns. States without Medicaid expansions (31% of the national population) were over-represented among cervical cancer and uterine cancer, but not ovarian cancer campaigns. CONCLUSIONS: Crowdfunding pages reveal patients fundraising for out-of-pocket costs in the thousands of dollars and a wide range of unmet financial needs based on cancer type.

Cost-Effectiveness of Unselected Multigene Germline and Somatic Genetic Testing for Epithelial Ovarian Cancer.

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.

The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.

BACKGROUND: Our study aimed to establish 'real-world' performance and cost-effectiveness of ovarian cancer (OC) surveillance in women with pathogenic germline BRCA1/2 variants who defer risk-reducing bilateral salpingo-oophorectomy (RRSO). METHODS: Our study recruited 875 female BRCA1/2-heterozygotes at 13 UK centres and via an online media campaign, with 767 undergoing at least one 4-monthly surveillance test with the Risk of Ovarian Cancer Algorithm (ROCA) test. Surveillance performance was calculated with modelling of occult cancers detected at RRSO. The incremental cost-effectiveness ratio (ICER) was calculated using Markov population cohort simulation. RESULTS: Our study identified 8 OCs during 1277 women screen years: 2 occult OCs at RRSO (both stage 1a), and 6 screen-detected; 3 of 6 (50%) were ≤stage 3a and 5 of 6 (83%) were completely surgically cytoreduced. Modelled sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV) for OC were 87.5% (95% CI, 47.3 to 99.7), 99.9% (99.9-100), 75% (34.9-96.8) and 99.9% (99.9-100), respectively. The predicted number of quality-adjusted life years (QALY) gained by surveillance was 0.179 with an ICER cost-saving of -£102,496/QALY. CONCLUSION: OC surveillance for women deferring RRSO in a 'real-world' setting is feasible and demonstrates similar performance to research trials; it down-stages OC, leading to a high complete cytoreduction rate and is cost-saving in the UK National Health Service (NHS) setting. While RRSO remains recommended management, ROCA-based surveillance may be considered for female BRCA-heterozygotes who are deferring such surgery.

Preimplantation genetic testing for BRCA gene mutation carriers: a cost effectiveness analysis.

BACKGROUND: Gynecologic oncologists should be aware of the option of conception through IVF/PGT-M for families with high BRCA related morbidity or mortality. Our objective was to investigate the cost-effectiveness of preimplantation genetic testing for selection and transfer of BRCA negative embryo in BRCA mutation carriers compared to natural conception. METHODS: Cost-effectiveness of two strategies, conception through IVF/PGT-M and BRCA negative embryo transfer versus natural conception with a 50% chance of BRCA positive newborn for BRCA mutation carriers was compared using a Markovian process decision analysis model. Costs of the two strategies were compared using quality adjusted life years (QALYs'). All costs were discounted at 3%. Incremental cost effectiveness ratio (ICER) compared to willingness to pay threshold was used for cost-effectiveness analysis. RESULTS: IVF/ PGT-M is cost-effective with an ICER of 150,219 new Israeli Shekels, per QALY gained (equivalent to 44,480 USD), at a 3% discount rate. CONCLUSIONS: IVF/ PGT-M and BRCA negative embryo transfer compared to natural conception among BRCA positive parents is cost effective and may be offered for selected couples with high BRCA mutation related morbidity or mortality. Our results could impact decisions regarding conception among BRCA positive couples and health care providers.

Cost-effectiveness of laparoscopic disease assessment in patients with newly diagnosed advanced ovarian cancer.

OBJECTIVE: To determine if laparoscopy is a cost-effective way to assess disease resectability in patients with newly diagnosed advanced ovarian cancer. METHODS: A cost-effectiveness analysis from a health care payer perspective was performed comparing two strategies: (1) a standard evaluation strategy, where a conventional approach to treatment planning was used to assign patients to either primary cytoreduction (PCS) or neoadjuvant chemotherapy with interval cytoreduction (NACT), and (2) a laparoscopy strategy, where patients considered candidates for PCS would undergo laparoscopy to triage between PCS or NACT based on the laparoscopy-predicted likelihood of complete gross resection. A microsimulation model was developed that included diagnostic work-up, surgical and adjuvant treatment, perioperative complications, and progression-free survival (PFS). Model parameters were derived from the literature and our published data. Effectiveness was defined in quality-adjusted PFS years. Results were tested with deterministic and probabilistic sensitivity analysis (PSA). The willingness-to-pay (WTP) threshold was set at $50,000 per year of quality-adjusted PFS. RESULTS: The laparoscopy strategy led to additional costs (average additional cost $7034) but was also more effective (average 4.1 months of additional quality-adjusted PFS). The incremental cost-effectiveness ratio (ICER) of laparoscopy was $20,376 per additional year of quality-adjusted PFS. The laparoscopy strategy remained cost-effective even as the cost added by laparoscopy increased. The benefit of laparoscopy was influenced by mitigation of serious complications and their associated costs. The laparoscopy strategy was cost-effective across a range of WTP thresholds. CONCLUSIONS: Performing laparoscopy is a cost-effective way to improve primary treatment planning for patients with untreated advanced ovarian cancer.

Prognostic impact of socioeconomic status on long-term survival of non-localized epithelial ovarian cancer ꟷ The Extreme study.

OBJECTIVE: To examine the influence of socioeconomic status (SES) on long-term survival of non-localized ovarian cancer. METHODS: All women in Denmark with a first diagnosis of non-localized epithelial ovarian cancer 1982-2007 were identified in the Cancer Registry and/or the Pathology Registry and followed up until December 2017. The survival probability was estimated after respectively 5 and 10 years, using so-called pseudo observations, and analyzed according to education, income, and marital status defined from nationwide registries. RESULTS: The study cohort included 6486 women, and the estimated 5- and 10-year survival probabilities were 21.4% and 12.7%, respectively. Compared to women with short education, the 5-year survival probability was 7% higher for women with medium (relative survival probability = 1.07, 95% CI: 0.97, 1.19) and long education (relative survival probability = 1.07, 95% CI: 0.93, 1.24). Compared with married women, the 5-year survival probability for divorced women/widower was slightly lower (0.85, 95% CI: 0.69, 1.04) and for unmarried women slightly higher (1.08, 95% CI: 0.94, 1.23). Finally, the probability of being alive 5 years after diagnosis was 1.09 times higher (95% CI: 0.95, 1.24) for medium-income women and 1.23 times higher (95% CI: 1.08, 1.41) for high-income women compared with low-income women. Similar patterns were observed for 10-year survival. CONCLUSIONS: Non-localized ovarian cancer patients have a poor prognosis. Our data suggest that among Danish women with advanced ovarian cancer, higher personal income is associated with slightly higher probability of long-term survival, whereas education and marital status did not affect the probability of long-term survival.

Cost-effectiveness of maintenance hormonal therapy in patients with advanced low grade serous ovarian cancer.

OBJECTIVES: To assess the cost-effectiveness of using maintenance hormonal therapy in patients with low grade serous ovarian cancer (LGSC). METHODS: A simulated decision analysis with a Markov decision model over a lifetime horizon was performed using the base case of a 47-year old patient with stage IIIC, LGSC following first-line treatment with primary cytoreductive surgery and adjuvant chemotherapy. Two treatment strategies were analyzed - maintenance daily letrozole until disease progression and routine observation. The analysis was from the perspective of the healthcare payer. Direct medical costs were estimated using public data sources and previous literature and were reported in adjusted 2018 Canadian dollars. The model estimated lifetime cost, quality-adjusted life years (QALY), life years (LY), median overall survival (OS), and number of recurrences with each strategy. Cost-effectiveness was compared using an incremental cost-effectiveness ratio (ICER). A strategy was considered cost-effective when the ICER was less than the willingness to pay (WTP) threshold of $50,000 CAD per QALY. Deterministic sensitivity analysis was performed to assess the impact of changing key clinical and cost variables. RESULTS: Maintenance letrozole was the preferred strategy with an associated lifetime cost of $69,985 CAD ($52,620 USD) and an observed improvement of 0.91 QALYs and 1.55 LYs. The ICER for letrozole maintenance therapy was an additional $11,037 CAD ($8298 USD) per QALY. The modeled median OS was 150 months with maintenance letrozole and 126 months in the observation strategy. The maintenance letrozole strategy resulted in 34% and 17% fewer first recurrences at 5-year and 10-year follow-up, respectively. CONCLUSION: Maintenance letrozole is a cost-effective treatment strategy in patients with advanced LGSC resulting in clinically-relevant improvement in QALYs, LYs, and fewer disease recurrences.

The preferences of women with ovarian cancer for oral versus intravenous recurrence regimens.

OBJECTIVE: To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. METHODS: A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%-60%); probability of PFS at 2 years (10%-20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). RESULTS: Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. CONCLUSIONS: These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens.

The impact of opportunistic salpingectomy on ovarian cancer mortality and healthcare costs: a call for universal insurance coverage.

BACKGROUND: Opportunistic salpingectomy at the time of hysterectomy or as an alternative to bilateral tubal ligation may reduce the incidence of ovarian cancer, because it has been demonstrated that most serous ovarian cancers begin in the fallopian tubes. However, salpingectomy at the time of sterilization is not always financially covered by third-party payers, and this represents a barrier to adoption. Routine salpingectomy has become more common but is not always practiced at the time of hysterectomy. OBJECTIVE: This study aimed to determine the impact of opportunistic salpingectomy as an alternative tubal ligation and routine salpingectomy at the time of hysterectomy on ovarian cancer mortality and overall cost. STUDY DESIGN: An 8-state Markov state transition model was constructed, including hysterectomy, tubal ligation, and ovarian cancer. Transition probabilities were informed by previously reported population data and include age-adjusted rates of elective sterilization and hysterectomy. This model was used to predict ovarian cancer incidence and the cost effectiveness of opportunistic salpingectomy. Testing of this model suggested that it accurately predicted overall life expectancy and closely predicted the rate of hysterectomy in the population. The model may underestimate the rate of tubal sterilization, making it conservative with respect to the benefits of salpingectomy. RESULTS: The recursive Markov model was run from ages 20 to 85 years in 1-year intervals with a half step correction and included age-adjusted rates of tubal ligation, hysterectomy (with and without oophorectomy), and ovarian cancer. The model predicts that opportunistic salpingectomy at the time of tubal ligation will reduce ovarian cancer mortality by 8.13%. Opportunistic salpingectomy at the time of hysterectomy will reduce ovarian cancer mortality by 6.34% for a combined decrease of 14.5%. Both strategies are cost effective when considering only the cost of the opportunistic salpingectomy. The excess cost of opportunistic salpingectomy at the time of tubal ligation was $433.91 with an incremental cost-effective ratio of $6401 per life-year and $5469 per quality-adjusted life year gained when adjusting for ovarian cancer with a utility of 0.64. The incremental cost-effective ratio for opportunistic salpingectomy during hysterectomy at a cost of $124.70 was $2006 per life-year and $1667 per quality-adjusted life year. When considering the impact of ovarian cancer prevention with respect to the cost of ovarian cancer treatment, opportunistic salpingectomy may produce a substantial healthcare savings. Utilizing a 3% discount rate, it is estimated that the total savings for universal salpingectomy could be as high as $445 million annually in the United States. A sensitivity analysis around the benefit of opportunistic salpingectomy suggests that this procedure will be cost effective even if salpingectomy provides only a modest reduction in the risk of ovarian cancer. CONCLUSION: It is estimated that universal opportunistic salpingectomy may prevent 1854 deaths per year from ovarian cancer and may reduce healthcare costs. Given these data, universal opportunistic salpingectomy should be considered at the time of tubal ligation and hysterectomy and covered by third-party payers.

Cost-effectiveness analysis comparing "PARP inhibitors-for-all" to the biomarker-directed use of PARP inhibitor maintenance therapy for newly diagnosed advanced stage ovarian cancer.

OBJECTIVES: Clinical trials evaluating universal PARP inhibitor (PARPi) frontline maintenance therapy for advanced stage ovarian cancer have reported progression-free survival (PFS) benefit. It is unclear whether PARPi maintenance therapy will universally enhance value (clinical benefits relative to cost of delivery). We compared a "PARPi-for-all" to a biomarker-directed frontline maintenance therapy approach as a value-based care strategy. METHODS: The cost of two frontline PARPi maintenance strategies, PARPi-for-all and biomarker-directed maintenance, was compared using modified Markov decision models simulating the study designs of the PRIMA, VELIA, and, PAOLA-1 trials. Outcomes of interest included overall costs and incremental cost-effectiveness ratios (ICERs) reported in US dollars per quality adjusted progression-free life-year (QA-PFY) gained. RESULTS: PARPi-for-all was more costly and provided greater PFS benefit than a biomarker-directed strategy for each trial. The mean cost per patient for the PARPi-for-all strategy was $166,269, $286,715, and $366,506 for the PRIMA, VELIA, and PAOLA-1 models, respectively. For the biomarker-directed strategy, the mean cost per patient was $98,188, $167,334, and $260,671 for the PRIMA, VELIA, and PAOLA-1 models. ICERs of PARPi-for-all compared to biomarker-directed maintenance were: $593,250/QA-PFY (PRIMA), $1,512,495/QA-PFY (VELIA), and $3,347,915/QA-PFY (PAOLA-1). At current drug pricing, there is no PFS improvement in a biomarker negative cohort that would make PARPi-for-all cost-effective compared to biomarker-directed maintenance. CONCLUSIONS: This study highlights the high costs of universal PARPi maintenance treatment, compared with a biomarker-directed PARPi strategy. Maintenance therapy in the front-line setting should be reserved for those with germline or somatic HRD mutations until the cost of therapy is significantly reduced.

Year 1: Experiences of a tertiary cancer centre following implementation of reflex BRCA1 and BRCA2 tumor testing for all high-grade serous ovarian cancers in a universal healthcare system.

OBJECTIVE: This study compares the rate and time to genetic referral, and patient uptake of germline genetic services, before and after implementation of reflex BRCA1/2 tumor testing for high-grade serous ovarian cancer (HGSOC) in a universal healthcare system. METHODS: A retrospective chart review of HSGOC patients diagnosed in the year before (PRE) and after (POST) implementation of reflex BRCA1/2 tumor testing was conducted. Clinical information (date/age at diagnosis, personal/family history of breast/ovarian cancer, cancer stage, primary treatment, tumor results) and dates of genetics referral, counseling, and germline testing were obtained. Incident rate ratios (IRR) and 95% CI were calculated using negative binomial regression. Time to referral was evaluated using Kaplan-Meier survival analysis. Fisher Exact tests were used to evaluate uptake of genetic services. RESULTS: 175 HGSOC patients were identified (81 PRE; 94 POST). Post-implementation of tumor testing, there was a higher rate of genetics referral (12.88 versus 7.10/1000 person-days; IRR = 1.60, 95% CI: 1.07-2.42) and a shorter median time from diagnosis to referral (59 days PRE, 33 days POST; p = .04). In the POST cohort, most patients were referred prior to receiving their tumor results (n = 63/77; 81.8%). Once referred, most patients attended genetic counseling (94.5% PRE, 97.6% POST; p = .418) and pursue germline testing (98.6% PRE; 100% POST; p = .455). CONCLUSIONS: Following implementation of reflex BRCA1/2 tumor testing for HGSOC, significant improvements to the rate and time to genetics referral were identified. Additional studies are needed to evaluate physician referral practices and the long-term impact of reflex tumor testing.

Patient preferences for maintenance PARP inhibitor therapy in ovarian cancer treatment.

OBJECTIVE: To measure preferences of women with ovarian cancer regarding risks, side effects, costs and benefits afforded by maintenance therapy (MT) with a poly ADP ribose polymerase (PARP) inhibitor. METHODS: A discrete-choice experiment elicited preferences of women with ovarian cancer regarding 6 attributes (levels in parentheses) relevant to decisions for MT versus treatment break: (1) overall survival (OS; 36, 38, 42 months); (2) progression-free survival (PFS; 15, 17, 21 months); (3) nausea (none, mild, moderate); (4) fatigue (none, mild, moderate); (5) probability of death from myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML; 0% to 10%); (6) monthly out-of-pocket cost ($0 to $1000). Participants chose between 2 variable MT scenarios and a static scenario representing treatment break, with multiple iterations. Random-parameters logit regression was applied to model choices as a function of attribute levels. RESULTS: 95 eligible participants completed the survey; mean age was 62, 48% had recurrence, and 17% were ever-PARP inhibitor users. Participants valued OS (average importance weight 24.5 out of 100) and monthly costs (24.6) most highly, followed by risk of death from MDS/AML (17.9), nausea (14.7), PFS (10.5) and fatigue (7.8). Participants would accept 5% risk of MDS/AML if treatment provided 2.2 months additional OS or 4.8 months PFS. Participants would require gains of 2.6 months PFS to accept mild treatment-related fatigue and 4.4 months to accept mild nausea. CONCLUSIONS: When considering MT, women with ovarian cancer are most motivated by gains in OS. Women expect at least 3-4 months of PFS benefit to bear mild side effects of treatment.

Factors associated with high-cost hospitalizations in elderly ovarian cancer patients.

OBJECTIVE: To characterize factors associated with high-cost inpatient admissions for ovarian cancer. METHODS: Operative hospitalizations for ovarian cancer patients ≥65 years of age were identified using the 2010-2017 National Inpatient Sample. Admissions with high-cost were defined as those incurring ≥90th percentile of hospitalization costs each year, while the remainder were considered low-cost. Multivariable logistic regression models were developed to assess independent predictors of being in the high-cost cohort. RESULTS: During the study period, an estimated 58,454 patients met inclusion criteria. 5827 patient admissions (9.98%) were classified as high-cost. Median hospitalization cost for this high-cost group was $55,447 (interquartile range (IQR) $46,744-$74,015) compared to $16,464 (IQR $11,845-$23,286, p < 0.001) for the low-cost group. Patients with high-cost admissions were more likely to have received open (adjusted odds ratio (AOR) 2.23, 1.31-3.79) or extended (AOR 5.64, 4.79-6.66) procedures and be admitted non-electively (AOR 3.32, 2.74-4.02). Being in the top income quartile (AOR 1.77, 1.39-2.27) was also associated with high-cost. Age and hospital factors, including bed size and volume of gynecologic oncology surgery, did not affect cost group. CONCLUSION: High-cost ovarian cancer admissions were three times more expensive than low-cost admissions. Fewer open and extended procedures with subsequently shorter lengths of stay may have contributed to decreasing inpatient costs over the study period. In this cohort of patients largely covered by Medicare, clinical factors outweigh socioeconomic factors as cost drivers. Understanding the relationship of disease-specific and social factors to cost will be important in informing future value-based quality improvement efforts in gynecologic cancer care.

Disparities in care among patients with low-grade serous ovarian carcinoma.

OBJECTIVE: Low-grade serous carcinoma (LGSC) is a rare histotype of ovarian cancer with a unique disease course. Little data exist regarding the influence of sociodemographic factors on diagnosis and outcomes in this disease. Our objective was to evaluate the associations between these factors and the clinical characteristics, treatment approaches, and survival in LGSC. METHODS: The National Cancer Database (NCDB) was queried for data between 2004 and 2015 on patients with LGSC. LGSC was inclusive of invasive, grade 1, serous carcinoma of the ovary, fallopian tube, or peritoneum. Patient demographics, insurance status, disease characteristics, treatment approach, and survival were evaluated. ANOVA, Chi Square, Kaplan-Meier, and Cox regression were used in the analysis. RESULTS: 3221 patients with LGSC were evaluated (89.5% White, 6.2% Black; 7.2% Hispanic, 92.8% non-Hispanic). Compared to Whites, Blacks were diagnosed younger (50.4 vs. 55.9 years, p < 0.01), received less chemotherapy (61.8% vs 67.0%, p = 0.04), and had less CA-125 elevation (OR 4.14 [1.26-13.57], p = 0.02). Compared to non-Hispanics, Hispanics were younger (49.5 vs. 55.8 years, p < 0.01) and received less chemotherapy (55% vs 67%, p < 0.001). In contrast to private insurance, government insurance was associated with a higher 30-day mortality (1.5% vs 0.01%, p < 0.001). Race/ethnicity were not predictive of OS, while older age (HR 1.013 [1.002-1.024], p = 0.03), advanced stage (HR 3.09 [2.15-4.43], p < 0.001), and government insurance (HR 2.33 [1.65-3.30], p < 0.001) were all independently associated with worse OS. CONCLUSIONS: Significant differences exist in the clinical characteristics, treatments, and outcomes of LGSC by sociodemographics, with Blacks and Hispanics being diagnosed younger and receiving less chemotherapy. Age, stage, and insurance status were predictive of overall survival.

Current status of hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer in the United States.

OBJECTIVES: 1.) To compare frequency of HIPEC use in ovarian cancer treatment before and after publication of the phase III study by van Driel et al. in January 2018. 2.) To compare associated rates of hospital-based outcomes, including length of stay, intensive care unit (ICU) admission, complications, and costs in ovarian cancer surgery with or without HIPEC. METHODS: We queried Vizient's administrative claims database of 550 US hospitals for ovarian cancer surgeries from January 2016-January 2020 using ICD-10 diagnosis and procedure codes. Sodium thiosulfate administration was used to identify HIPEC cases according to the published protocol. Student t-tests and relative risk (RR) were used to compare continuous variables and contingency tables, respectively. RESULTS: 152 ovarian cancer patients had HIPEC at 39 hospitals, and 20,014 ovarian cancer patients had surgery without HIPEC at 256 hospitals. Following the trial publication, 97% of HIPEC cases occurred. During the index admission, HIPEC patients had longer median length of stay (8.4 vs. 5.7 days, p < 0.001) and higher percentage of ICU admissions (63.1% vs. 11.0%, p < 0.001) and complication rates (RR = 1.87, p = 0.002). Index admission direct costs ($21,825 vs. $12,038, p < 0.001) and direct cost index (observed/expected costs) (1.87 vs. 1.11, p < 0.001) were also greater in the HIPEC patients. No inpatient deaths or 30-day readmissions were identified after HIPEC. CONCLUSIONS: Use of HIPEC for ovarian cancer increased in the US after publication of a phase III clinical trial in a high-impact journal, though the absolute number of cases remains modest. Incorporation of HIPEC was associated with increased cost, hospital length of stay, ICU admission, and hospital-acquired complication rates. Further studies are needed in order to evaluate long-term outcomes, including morbidity and survival.

Cost-effectiveness of niraparib, rucaparib, and olaparib for treatment of platinum-resistant, recurrent ovarian carcinoma.

BACKGROUND: Olaparib was approved on December 19, 2014 by the US FDA as 4th-line therapy (and beyond) for patients with germline BRCA1/2 mutations; rucaparib was approved on December 19, 2016 as 3rd-line therapy (and beyond) for germline or somatic BRCA1/2-mutated recurrent disease. On October 23, 2019, niraparib was approved for treatment of women with damaging mutations in BRCA1/2 or other homologous recombination repair genes who had been treated with three or more prior regimens. We compared the cost-effectiveness of PARPi(s) with intravenous regimens for platinum-resistant disease. METHODS: Median progression-free survival (PFS) and toxicity data from regulatory trials were incorporated in a model which transitioned patients through response, hematologic complications, non-hematologic complications, progression, and death. Using TreeAge Pro 2017, each PARPi(s) was compared separately to non­platinum-based and bevacizumab-containing regimens. Costs of IV drugs, managing toxicities, infusions, and supportive care were estimated using 2017 Medicare data. Incremental cost-effectiveness ratios (ICERs) were calculated and PFS was reported in quality adjusted life months for platinum-resistant populations. RESULTS: Non­platinum-based intravenous chemotherapy was most cost effective ($6,412/PFS-month) compared with bevacizumab-containing regimens ($12,187/PFS-month), niraparib ($18,970/PFS-month), olaparib ($16,327/PFS-month), and rucaparib ($16,637/PFS-month). ICERs for PARPi(s) were 3-3.5× times greater than intravenous non­platinum-based regimens. CONCLUSION: High costs of orally administered PARPi(s) were not mitigated or balanced by costs of infusion and managing toxicities of intravenous regimens typically associated with lower response and shorter median PFS. Balancing modest clinical benefit with costs of novel therapies remains problematic and could widen disparities among those with limited access to care.

Real world experience of poly (ADP-ribose) polymerase inhibitor use in a community oncology practice.

OBJECTIVE: This study aims to describe the real-world experience, including the clinical and financial burden, associated with PARP inhibitors in a large community oncology practice. METHODS: Retrospective chart review identified patients prescribed olaparib, niraparib or rucaparib for maintenance therapy or treatment of recurrent ovarian, primary peritoneal or fallopian tube cancer across twelve gynecologic oncologists between December 2016 and November 2018. Demographic, financial and clinical data were extracted. One PARP cycle was defined as a single 28-day period. For patients treated with more than one PARPi, each course was described separately. RESULTS: A total of 47 patients and 506 PARP cycles were identified (122 olaparib, 24%; 89 rucaparib, 18%; 294 niraparib, 58%). Incidence of grade ≥ 3 adverse events were similar to previously reported. Toxicity resulted in dose interruption, reduction and discontinuation in 69%, 63% and 29% respectively. Dose interruptions were most frequent for niraparib but resulted in fewer discontinuations (p-value 0.01). Mean duration of use was 7.46 cycles (olaparib 10.52, rucaparib 4.68, niraparib 7.34). Average cost of PARPi therapy was $8018 per cycle. A total of 711 phone calls were documented (call rate 1.4 calls/cycle) with the highest call volume required for care coordination, lab results and toxicity management. CONCLUSIONS: Although the toxicity profile was similar to randomized clinical trials, this real-world experience demonstrated more dose modifications and discontinuations for toxicity management than previously reported. Furthermore, the clinical and financial burden of PARP inhibitors may be significant and future studies should assess the impact on patient outcomes.

Niraparib maintenance in frontline management of ovarian cancer: a cost effectiveness analysis.

OBJECTIVES: Niraparib maintenance after frontline chemotherapy for advanced ovarian cancer extends progression free survival. The objective of this study was to determine the cost effectiveness of niraparib maintenance therapy in patients with newly diagnosed ovarian cancer. METHODS: Decision analysis models compared the cost of observation versus niraparib maintenance following chemotherapy for five groups: all newly diagnosed ovarian cancer patients (overall), those with homologous recombination deficiency, those harboring BRCA mutations (BRCA), homologous recombination deficiency patients without BRCA mutations (homologous recombination deficiency non-BRCA), and non-homologous recombination deficiency patients. Drug costs were estimated using average wholesale prices. Progression free survival was estimated from published data and used to estimate projected overall survival. Incremental cost effectiveness ratios per quality adjusted life year were calculated. Sensitivity analyses varying the cost of niraparib were performed. The willingness-to-pay threshold was set at US$100 000 per quality adjusted life year saved. RESULTS: For the overall group, the cost of observation was US$5.8 billion versus $20.5 billion for niraparib maintenance, with an incremental cost effectiveness ratio of $72 829. For the homologous recombination deficiency group, the observation cost was $3.0 billion versus $14.8 billion for niraparib maintenance (incremental cost effectiveness ratio $56 329). Incremental cost effectiveness ratios for the BRCA, homologous recombination deficiency non-BRCA, and non-homologous recombination deficiency groups were $58 348, $50 914, and $88 741, respectively. For the overall and homologous recombination deficiency groups, niraparib remained cost effective if projected overall survival was 2.2 and 1.5 times progression free survival, respectively. CONCLUSIONS: For patients with newly diagnosed ovarian cancer, maintenance therapy with niraparib was cost effective. Cost effectiveness was improved when analyzing those patients with homologous recombination deficiency and BRCA mutations. Efforts should continue to optimize poly-ADP-ribose polymerase utilization strategies.

Quality of life and ability to work in ovarian cancer patients in Slovakia.

The aim of this paper was to find out the association of relevant factors on health-related quality of life (HRQOL) among ovarian cancer patients and their ability to work. Analyzed data were prospectively collected on 123 ovarian cancer patients enrolled across multiple oncology practices in Slovakia. We examined knowledge about the disease, negative perceptions related to health care, ability to work and social and economic ranking. HRQOL measurements included quality of life based on a numeric scale (1-worst, 10-best) and selected aspects from QoL-Ov28 questionnaire. We have used non-parametric Friedman and Dunne pairwise comparison tests to detect differences in HRQOL and the ability to work. Spearman correlation was used to measure the strength of association between variables. With hindsight, patients identified first signs of disease 3.6 months prior to diagnosis, with median duration of disease being 3.1 years. HRQOL was significantly different at various points during cancer journey; between current state and at diagnosis (4.19), between current state and at time without cancer or at time in full health (8.94, 9.52 respectively). Similarly, significant differences were noted in patients' current work ability (WA) compared to WA at diagnosis, or at time without cancer or in full health (4.2, 9.07, 9.58). The highest correlation of HRQOL was found in relation to current ability to work (r = 0.87) and in impact of cancer treatment (r = 0.66). Medium correlation was noted with visits to oncology clinics, knowledge about cancer, salary, future expectations or perceived quality of life of relatives (r < 0.51). Low correlation (r < 0.3) was found with other aspects related to healthcare (nursing care, general practitioner appointments) or demographics (age, number of children) and others. Patients were willing to pay monthly for curative treatment €191.84 from an average monthly salary €470.84 (41%). Ovarian cancer diagnosis has a significant impact on HRQOL and WA and both are positively highly correlated. Ovarian cancer patients are willing to give significant share of their monthly salary for treatment leading to cure.