Reducing renal function assessment prior to platinum-based chemotherapy: a real-world evaluation.

BACKGROUND: Platinum-based chemotherapy, a widely used backbone of systemic cytotoxic anticancer treatment, is associated with nephrotoxicity. Currently, renal function is generally assessed prior to each administration of cisplatin or carboplatin, but there is no guideline regarding the frequency of renal function determination. OBJECTIVE: The primary objective was to determine the median time to a clinically relevant dosage adjustment (>10%) due to change in renal function in patients treated with cisplatin and carboplatin. Secondly, variables influencing changes in renal function were assessed. METHODS: We conducted a retrospective analysis of serial renal function assessments in platinum-treated patients with cancer in two academic medical centers, using a query to extract data from the electronic health records between 2017 and 2019. RESULTS: In total, 512 patients receiving cisplatin and 628 patients receiving carboplatin were included. In total, 15% of all cisplatin-treated patients were found to have a renal function less than 60 mL/min at least once during treatment, with a median time to renal function decline of 67 days (range 5-96 days), which did not differ between treatment regimens. For carboplatin 21% of patients were found to have had a dosage variation of more than 10% at least once during treatment, with a median time-to-event period of 64 days (range 5-100 days). INTERPRETATION: Dose adjustments during platinum-based chemotherapy resulting from renal function decline occur after a median time of ≥64 days. Our data provide substantiated guidance to recommend renal function assessment during platinum-based chemotherapy in clinically stable patients to once every 3 weeks.

Progress towards universal health coverage and inequalities in infant mortality: an analysis of 4·1 million births from 60 low-income and middle-income countries between 2000 and 2019.

BACKGROUND: Expanding universal health coverage (UHC) might not be inherently beneficial to poorer populations without the explicit targeting and prioritising of low-income populations. This study examines whether the expansion of UHC between 2000 and 2019 is associated with reduced socioeconomic inequalities in infant mortality in low-income and middle-income countries (LMICs). METHODS: We did a retrospective analysis of birth data compiled from Demographic and Health Surveys (DHSs). We analysed all births between 2000 and 2019 from all DHSs available for this period. The primary outcome was infant mortality, defined as death within 1 year of birth. Logistic regression models with country and year fixed effects assessed associations between country-level progress to UHC (using WHO's UHC service coverage index) and infant mortality (overall and by wealth quintile), adjusting for infant-level, mother-level, and country-level variables. FINDINGS: A total of 4 065 868 births to 1 833 011 mothers were analysed from 177 DHSs covering 60 LMICs between 2000 and 2019. A one unit increase in the UHC index was associated with a 1·2% reduction in the risk of infant death (AOR 0·988, 95% CI 0·981-0·995; absolute measure of association, 0·57 deaths per 1000 livebirths). An estimated 15·5 million infant deaths were averted between 2000 and 2019 because of increases in UHC. However, richer wealth quintiles had larger associated reductions in infant mortality from UHC (quintile 5 AOR 0·983, 95% CI 0·973-0·993) than poorer quintiles (quintile 1 0·991, 0·985-0·998). In the early stages of UHC, UHC expansion was generally beneficial to poorer populations (ie, larger reductions in infant mortality for poorer households [infant deaths per 1000 per one unit increase in UHC coverage: quintile 1 0·84 vs quintile 5 0·59]), but became less so as overall coverage increased (quintile 1 0·64 vs quintile 5 0·57). INTERPRETATION: Since UHC expansion in LMICs appears to become less beneficial to poorer populations as coverage increases, UHC policies should be explicitly designed to ensure lower income groups continue to benefit as coverage expands. FUNDING: UK National Institute for Health and Care Research.

Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer.

Background: A recent phase III clinical trial (NCT03981796) evaluated the efficacy and safety of dostarlimab combined with carboplatin-paclitaxel (DOS-CP) compared to placebo combined with carboplatin-paclitaxel (PLB-CP) as a first-line treatment for advanced endometrial cancer (EC). The NCT03981796 trial demonstrated that DOS-CP significantly improved progression-free survival and overall survival of patients with advanced EC while maintaining an acceptable safety profile. However, DOS-CP is expensive and its cost-effectiveness has not been evaluated. This study aims to evaluate the cost-effectiveness of DOS-CP compared to PLB-CP as a first-line treatment for advanced EC from the perspective of the Chinese healthcare system. Methods: A Markov model with three health states was developed to evaluate the cost-effectiveness of DOS-CP as a first-line treatment for advanced EC. Clinical efficacy data were derived from the NCT03981796 trial, and drug costs were determined based on national tender prices. Other costs and utility values were obtained from published literature. The outcomes assessed included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of the model was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis. Results: In comparison to PLB-CP, the ICER of DOS-CP was $98,276.61/QALY for the overall population, $53,063.61/QALY for the dMMR subgroup, and $124,088.56/QALY for the pMMR subgroup. All of these ICER values were higher than the willingness-to-pay threshold of $38,201 per QALY. The most important variable that affected the results of the model was the discount rate, the cost of dostarlimab, and the utility value for progressive disease. Conclusion: From the perspective of the Chinese healthcare system, DOS-CP is unlikely to be a cost-effective first-line treatment option for advanced EC.

Clinical and Economic Outcomes in Patients With Metastatic Urothelial Carcinoma Receiving First-Line Systemic Treatment (the IMPACT UC I Study).

BACKGROUND: The IMPACT UC I study assessed real-world treatment patterns, outcomes, healthcare resource utilization (HCRU), and costs in patients with metastatic urothelial carcinoma (mUC) receiving first-line (1L) systemic treatment after the FDA approval of 1L immune checkpoint inhibitor (ICI) monotherapy. PATIENTS AND METHODS: This retrospective study used 100% Medicare fee-for-service claims from 1/1/2015 to 6/30/2019 to identify patients aged ≥18 years diagnosed with UC with evidence of metastatic disease, continuously enrolled for 6 months before and after initial diagnosis. Patients were grouped by 1L treatment: cisplatin-containing chemotherapy, carboplatin-containing chemotherapy, ICI monotherapy, or nonplatinum-containing therapy. Unadjusted time on 1L treatment (TOT), overall survival (OS), HCRU, and total healthcare costs were analyzed. RESULTS: Of 18 888 patients with mUC, 8630 (45.7%) had received identified 1L systemic treatment; platinum-containing chemotherapy was the most common (cisplatin-containing chemotherapy, 37.6%; carboplatin-containing chemotherapy, 30.2%). Cisplatin- and carboplatin-containing chemotherapy had the shortest time-to-treatment initiation (median, 1.7-3.0 months) and longest TOT (median, 4.0-4.3 months). Median OS was longest with cisplatin-containing chemotherapy (20.0 months) and shortest with ICI monotherapy (7.6 months). Cisplatin- and carboplatin-containing chemotherapy were associated with highest HCRU; total healthcare costs were approximately 2-fold higher with ICI monotherapy vs other 1L treatments ($10 359 vs $5042-$5709 per patient per month). CONCLUSION: 1L platinum-containing chemotherapy resulted in the longest median OS and highest HCRU, whereas 1L ICI treatment had the shortest median OS and the highest costs. Over 50% of patients diagnosed with advanced UC (aUC) received no systemic therapy, highlighting the importance of optimal 1L treatment decisions in aUC.

Cost-effectiveness analysis of tumor molecular testing in stage III endometrial cancer.

BACKGROUND: Standard of care for adjuvant treatment of stage III endometrial cancer includes chemotherapy and radiation. In addition to stage, tumor molecular profiles may predict treatment outcomes, and prospective clinical trials are ongoing. However, tumor molecular testing is costly and time-consuming. Our objective was to evaluate the cost-effectiveness of tumor molecular testing in stage III endometrial cancer. METHODS: A Markov decision model compared two strategies for stage III endometrial cancer: Tumor Molecular Testing (TMT) versus No TMT. TMT included sequential POLE next generation sequencing, mismatch repair immunohistochemistry (IHC), and p53 IHC. POLE-mutated patients were assigned to adjuvant radiation therapy; all others including controls were assigned to adjuvant chemoradiation. First recurrences were treated with 6 cycles of carboplatin and paclitaxel. Second recurrences were treated with pembrolizumab alone for mismatch repair deficient patients and both pembrolizumab and lenvatinib for other patients. Sensitivity analyses were performed to test model robustness. RESULTS: Compared to No TMT, TMT was cost saving with equivalent effectiveness. On one-way sensitivity analysis, TMT remained cost saving over all parameter ranges. TMT was also favored on probabilistic sensitivity analysis in 80% of iterations at a willingness-to-pay threshold of $100,000/quality adjusted life-year (QALY) gained. However, when TMT was compared to mismatch repair IHC alone, TMT cost $182,798/QALY gained. CONCLUSIONS: In this model of patients with stage III endometrial cancer, TMT was cost saving compared to No TMT. However, when compared to mismatch repair IHC alone, TMT was economically unfavorable.

Fertility and prognosis assessment between bleomycin/etoposide/cisplatin and paclitaxel/carboplatin chemotherapy regimens in the conservative treatment of malignant ovarian germ cell tumors: a multicenter and retrospective study.

OBJECTIVE: To evaluate the impact of bleomycin/etoposide/cisplatin (BEP) and paclitaxel/carboplatin (PC) chemotherapy regimens on the fertility and prognostic outcomes in malignant ovarian germ cell tumor (MOGCT) patients who underwent fertility-sparing surgery (FSS). METHODS: A propensity score matching algorithm was performed between the BEP and PC groups. The χ² test and the Kaplan-Meier method were used to compare the fertility outcome, disease-free survival (DFS) and overall survival (OS). The Cox proportional hazards regression analysis was used to identify risk factor of DFS. RESULTS: We included 213 patients, 185 (86.9%) underwent BEP chemotherapy, and 28 (13.1%) underwent PC chemotherapy. The median age was 22 years (range, 8-44 years), and the median follow-up period was 63 months (range, 2-191 months). Fifty-one (29.3%) patients had a pregnancy plan, and 35 (85.4%) delivered successfully. In the before and after propensity score matching cohorts, there were no significant differences in spontaneous abortion, selective termination of pregnancy, during-pregnancy status, and live birth between the BEP and PC groups (p>0.05). Fourteen (6.6%) patients experienced recurrence, including 11 (5.9%) in the BEP group and 3 (10.7%) in the PC group. Four (1.9%) patients in the BEP group died. Kaplan-Meier analysis revealed no significant differences in DFS (p=0.328) and OS (p=0.446) between the BEP and PC groups, and the same survival results were observed in the after matching cohort. CONCLUSION: The PC regimen is as safe as the BEP regimen for MOGCT patients with fertility preservation treatment, and no differences were observed in fertility and clinical prognosis.

Treatment Patterns and Outcomes in Resected Early-stage Non-small Cell Lung Cancer: An Analysis of the SEER-Medicare Data.

BACKGROUND: As the non-small cell lung cancer (NSCLC) adjuvant treatment landscape evolves, an evaluation of treatment patterns and outcomes of patients with early-stage, resected NSCLC eligible for adjuvant treatment in routine clinical practice is needed to better understand the unmet needs in this patient population. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2019) were used to identify patients with newly diagnosed stage IB (tumor size ≥4cm)-IIIA (AJCC 7th edition) NSCLC who received primary surgery (index date). We assessed adjuvant treatment patterns, real-world disease-free survival (rwDFS; time from index date to first recurrence or death) and overall survival (OS; time from index date to death), and loco-regional recurrence pattern and treatment distribution. RESULTS: Among 1761 patients with primary surgery, mean age was 73.8 years; 47.9% were male; and 83.9% were white. Approximately 41% of patients received adjuvant chemotherapy; median time from surgery to adjuvant chemotherapy initiation was 48 days, and the most frequently observed adjuvant chemotherapy regimen was carboplatin+paclitaxel (24.5%). In the overall population, median rwDFS was 24.8 months and OS was 76.7 months; 5-year rwDFS and OS rates were 29.3% and 57.5%, respectively. Among 392 patients with loco-regional recurrence, the most frequently observed treatment was curative radiation monotherapy (28.2%). CONCLUSION: Despite clinical guideline recommendations, rate of adjuvant chemotherapy among patients with resected early-stage NSCLC was low in clinical practice. Overall, among patients with early-stage NSCLC treated with conventional primary surgery, poor survival outcomes were observed, highlighting the need for and importance of more effective adjuvant treatments.

Cost-Effectiveness of Pharmacologic Treatment Options for Women With Endocrine-Refractory or Triple-Negative Metastatic Breast Cancer.

PURPOSE: Treatments for endocrine-refractory or triple-negative metastatic breast cancer (mBC) are modestly effective at prolonging life and improving quality of life but can be extremely expensive. Given these tradeoffs in quality of life and cost, the optimal choice of treatment sequencing is unclear. Cost-effectiveness analysis can explicitly quantify such tradeoffs, enabling more informed decision making. Our objective was to estimate the societal cost-effectiveness of different therapeutic alternatives in the first- to third-line sequences of single-agent chemotherapy regimens among patients with endocrine-refractory or triple-negative mBC. METHODS: Using three dynamic microsimulation models of 10,000 patients each, three cohorts were simulated, based upon prior chemotherapy exposure: (1) unexposed to either taxane or anthracycline, (2) taxane- and anthracycline-exposed, and (3) taxane-exposed/anthracycline-naive. We focused on the following single-agent chemotherapy regimens as reasonable and commonly used options in the first three lines of therapy for each cohort, based upon feedback from oncologists treating endocrine-refractory or triple-negative mBC: (1) for taxane- and anthracycline-unexposed patients, paclitaxel, capecitabine (CAPE), or pegylated liposomal doxorubicin; (2) for taxane- and anthracycline-exposed patients, Eribulin, CAPE, or carboplatin; and (3) for taxane-exposed/anthracycline-naive patients, pegylated liposomal doxorubicin, CAPE, or Eribulin. RESULTS: In each cohort, accumulated quality-adjusted life-years were similar between regimens, but total societal costs varied considerably. Sequences beginning first-line treatment with paclitaxel, carboplatin, and CAPE, respectively, for cohorts 1, 2, and 3, had lower costs and similar or slightly better outcomes compared with alternative options. CONCLUSION: In this setting where multiple single-agent chemotherapy options are recommended by clinical guidelines and share similar survival and adverse event trajectories, treatment sequencing approaches that minimize costs early may improve the value of care.

Cost Effectiveness of Adding Pembrolizumab to Platinum and Fluoropyrimidine-Based Chemotherapy as First-Line Treatment for Advanced Esophageal Cancer: A US Healthcare Payer's Perspective.

BACKGROUND AND OBJECTIVE: Pembrolizumab plus cisplatin and fluorouracil demonstrated superior efficacy and comparable safety compared with fluorouracil and cisplatin (FP) as first-line treatment for locally advanced unresectable or metastatic carcinoma of the esophagus and gastroesophageal junction adenocarcinoma in a phase III trial (KEYNOTE-590). This study evaluated the cost effectiveness of pembrolizumab plus FP versus FP and versus a blended chemotherapy comparator including FP, carboplatin plus paclitaxel, FOLFOX, FOLFIRI, docetaxel plus FP, trastuzumab plus FP, and trastuzumab plus FOLFOX from a US healthcare payer's perspective. METHODS: A partitioned survival model was developed with three health states (progression-free, progressive disease, and death). Overall survival, progression-free survival, time on treatment, and adverse events were informed by patient-level data from KEYNOTE-590. The blended chemotherapy comparator reflected the current US treatment landscape and was assumed to have similar efficacy and safety as FP. Health utilities were estimated using linear mixed-effects models based on EQ-5D-5L data from the trial. Resource use and cost inputs (2020 US dollars) were based on US standard sources and literature. Costs, life-years, and quality-adjusted life-years (QALYs) discounted at 3.0% per year and incremental cost-effectiveness ratio were outcomes in the model. Sensitivity and scenario analyses were conducted to assess the robustness of base-case results. RESULTS: Compared with FP, pembrolizumab plus FP produced a mean gain of 0.86 life-year and 0.77 QALY with additional costs of $112,630 over 37.6 years, yielding an incremental cost-effectiveness ratio of $147,097 per QALY. Results were similar when the intervention was pembrolizumab plus alternative chemotherapies or when blended chemotherapy became the comparator. Results were most sensitive to different overall survival extrapolation approaches. CONCLUSIONS: Our analysis suggests that pembrolizumab plus chemotherapy extended life-years and QALYs and is cost effective compared with chemotherapy alone as a first-line treatment for advanced esophageal cancer in the USA given a willingness-to-pay threshold of $150,000 per QALY.

Patterns of care amongst older adults diagnosed with locally advanced esophageal cancer: A cohort study.

INTRODUCTION: Since the early 2010s, neoadjuvant chemoradiation followed by esophagectomy (trimodal therapy) has been a recommended treatment for patients diagnosed with locally advanced esophageal cancer. However, it may also add treatment-related toxicity, particularly for older adults with significant comorbidity and frailty burdens. We examined contemporary patterns of care in older adults, which have not been well characterized. MATERIALS AND METHODS: We used the Surveillance Epidemiology and End Results-Medicare database to identify a cohort of US adults aged 66 years and older diagnosed with incident locally advanced esophageal cancer between 2004 and 2017. Calendar year age-standardized percentages of treatment receipt were calculated. Joinpoint regression was used to detect temporal trends in treatment receipt. Descriptive associations between patient factors and treatment were assessed. Trend analyses quantified how the percentage of trimodal and definitive chemoradiation (no surgery) patients receiving cisplatin-based, carboplatin-based, and other chemotherapy regimens evolved over time. RESULTS: In total, 4332 adults aged ≥66 years with locally advanced esophageal cancer were included. The age-standardized percentage of patients receiving trimodal therapy increased from 16.7% in 2004 to 26.1% in 2017 (annual percent change = 3.5%; 95% confidence interval [CI], 0.7%-6.4%) in adenocarcinomas and from 7.3% in 2004 to 9.1% in 2017 (annual percent change = 0.4%; 95% CI, -4.1%-5.1%) in squamous cell carcinomas. By 2017, definitive chemoradiation became the most frequently used treatment modality for adenocarcinomas (49.8%; 95% CI, 43.5-56.0) and squamous cell carcinomas (59.5%; 95% CI, 50.8-68.2). Patients with higher comorbidity and frailty burdens were less likely to be treated with trimodal therapy. Amongst patients receiving chemoradiation as part of their treatment, a large and swift channeling away from cisplatin and towards carboplatin-based regimens was observed. DISCUSSION: In practice, definitive chemoradiation is the most commonly received treatment by older adults with locally advanced esophageal cancer. Four out of five older adults do not receive trimodal therapy, some of whom are potentially undertreated.

Assessment of quality of life among advanced ovarian cancer patients in a tertiary care hospital in India.

PURPOSE: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India. METHODS: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve. RESULTS: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being. CONCLUSION: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers.

Cost-effectiveness analysis of pembrolizumab for treatment of US patients with persistent, recurrent, or metastatic cervical cancer.

OBJECTIVE: The effectiveness of pembrolizumab for persistent, recurrent, or metastatic cervical cancer has been demonstrated. We aimed to evaluate its cost-effectiveness from the United States (US) healthcare payers perspective. METHODS: A partitioned survival model over a 30-year lifetime horizon was developed to compare the cost and effectiveness of pembrolizumab versus placebo based on clinical data from the KEYNOTE-826 phase 3 randomized trial. Costs and health state utilities were obtained from literature and publicly available databases. The incremental cost-effectiveness ratio (ICER) was measured. One-way and probabilistic sensitivity analyses were conducted. RESULTS: For the Intention-to-Treat patients, pembrolizumab was associated with an additional 0.74 quality-adjusted life-year (QALY) at an additional cost of $182,271 when compared with placebo. The ICER was $247,663/QALY. For patients with a programmed death-ligand 1 combined positive score ≥ 1 and 10, the ICER was $253,322/QALY and $214,212/QALY, respectively. One-way sensitivity analyses showed that pembrolizumab had the greatest impact on the ICER. Probabilistic sensitivity analyses showed that the probability of pembrolizumab being cost-effective was zero at the current willingness-to-pay threshold of $150,000/QALY. The price of pembrolizumab had to reduce at least to $28.336 (55.8% of the current price) for it to be cost-effective in a 50% of chance. CONCLUSION: The addition of pembrolizumab to chemotherapy is costly and might not be cost-effective for persistent, recurrent, or metastatic cervical cancer at the current price in the US.

Cost-Effectiveness of Pembrolizumab Versus Carboplatin and Paclitaxel in Patients With Unresectable or Metastatic Melanoma After First-Line Treatment in China.

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of pembrolizumab compared with standard-of-care chemotherapy (paclitaxel + carboplatin [PC]) in patients with unresectable or metastatic melanoma after first-line treatment from a Chinese healthcare system perspective. METHODS: We conducted a partitioned-survival model with a 1-week cycle length and a 20-year base-case time horizon. Piecewise parametric models were fitted to KEYNOTE-006 trial data to estimate progression-free survival and overall survival for pembrolizumab, and a network meta-analysis was used to estimate the clinical outcomes for standard of care. Quality-adjusted life-years (QALYs) were calculated using EQ-5D data from KEYNOTE-006, applying Chinese-specific utility tariffs. Costs included drug acquisition, administration, adverse events, and disease management, reflecting the Chinese pricing system. Chinese-specific disease management costs were estimated based on clinical opinion on health state resource use and chemotherapy-related adverse events. Costs and outcomes were discounted at 5% annually. Multiple deterministic and probabilistic sensitivity analyses were performed to test the robustness of the results. RESULTS: In the base-case analysis, the treatment of pembrolizumab is estimated to yield 2.63 life-years (LYs) and 2.24 QALYs at an incremental cost of ¥372 316.46 versus PC. The incremental costs per LY and per QALY were ¥141 771.00 and ¥165 865.69, respectively, the latter being below a threshold of 3 times the per capita gross domestic product (ï¿¥193 932) in China, deemed as cost-effective according to the World Health Organization threshold. These findings were robust against a wide range of sensitivity analyses. CONCLUSIONS: Pembrolizumab is projected as cost-effective compared with PC in patients with unresectable or metastatic melanoma after first-line treatment in China.

Cervical cancer treatment in Rwanda: Resource-driven adaptations, quality indicators, and patient outcomes.

OBJECTIVE: Most cervical cancer cases and deaths occur in low- and middle-income countries, yet clinical research from these contexts is significantly underrepresented. We aimed to describe the treatment quality, resource-driven adaptations, and outcomes of cervical cancer patients in Rwanda. METHODS: A retrospective cohort study was conducted of all patients with newly diagnosed cervical cancer enrolled between April 2016 and June 2018. Data were abstracted from medical records and analyzed using descriptive statistics, Kaplan Meier methods, and Cox proportional hazards regression. RESULTS: A total of 379 patients were included; median age 54 years, 21% HIV-infected. A majority (55%) had stage III or IV disease. Thirty-four early-stage patients underwent radical hysterectomy. Of 254 patients added to a waiting list for chemoradiation, 114 ultimately received chemoradiation. Of these, 30 (26%) received upfront chemoradiation after median 126 days from diagnosis, and 83 (73%) received carboplatin/paclitaxel while waiting, with a median 56 days from diagnosis to chemotherapy and 207 days to chemoradiation. There was no survival difference between the upfront chemoradiation and prior chemotherapy subgroups. Most chemotherapy recipients (77%) reported improvement in symptoms. Three-year event-free survival was 90% with radical hysterectomy (95% CI 72-97%), 66% with chemoradiation (95% CI 55-75%), and 12% with chemotherapy only (95% CI 6-20%). CONCLUSIONS: Multi-modality treatment of cervical cancer is effective in low resource settings through coordinated care and pragmatic approaches. Our data support a role for temporizing chemotherapy if delays to chemoradiation are anticipated. Sustainable access to gynecologic oncology surgery and expanded access to radiotherapy are urgently needed.

Serplulimab plus chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: A cost-effectiveness analysis.

Introduction: The ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin [EC]) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immuno-chemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail. Methods: The cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Model instability was interrogated through one-way and probabilistic sensitivity analyses. Results: Serplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY ($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases. Conclusion: From a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients.

Pharmacokinetic and safety assessment of carboplatin-impregnated calcium sulfate hemihydrate beads in eight rats.

OBJECTIVE: Evaluate local tissue toxicity and plasma platinum (Pt) in vivo after subcutaneous implantation of carboplatin-impregnated calcium sulfate hemihydrate (CI-CSH) beads. STUDY DESIGN: In vivo experimental study. ANIMALS: Eight male Sprague-Dawley rats. METHODS: CI-CSH beads were implanted subcutaneously (5 mg carboplatin/rat; 13.5 mg/kg carboplatin; 7.08 mg/kg Pt; 1.18 mg/m2 Pt) in eight rats (d0). Wound healing (daily), radiographic bead dissolution (weekly), systemic Pt uptake (plasma-Pt), local tissue Pt (d28), and histologic changes compared to nonincised and incised catheterization sites (d28) were assessed. Blood and tissue samples were analyzed by inductively coupled plasma mass spectrometry for Pt, and pharmacokinetic analysis was performed using noncompartmental methods. RESULTS: One rat died at d10, the remainder survived until d28. No wound complications were seen. The CI-CSH implantation site had higher histopathology scores than the other sites for necrosis (p = .013) and fibrosis (p = .013). Beads decreased in density radiographically (d0 to d28) (p = .062). Peak plasma-Pt concentration was 225.78 ng/ml at 12 h, and decreased over time, but Pt was still detectable on d28. The elimination half-life was 5.03 ± 1.13 days. Only 1.69% of implanted Pt remained in the beads at d28. CONCLUSIONS: CI-CSH beads incited microscopic mild inflammation but wound healing was not impaired. Pt was absorbed systemically and the release from the beads was near complete at d28. CLINICAL SIGNIFICANCE: Piled CI-CSH bead implantation is well tolerated in rats with similar elution profile as previously described. Beads were radiographically visible at d28. Minimal Pt was detected systemically suggesting Pt release does not match bead dissolution.

Pembrolizumab and lenvatinib versus carboplatin and paclitaxel as first-line therapy for advanced or recurrent endometrial cancer: A Markov analysis.

OBJECTIVE: To determine the cost effectiveness of pembrolizumab/lenvatinib (P/L) versus standard-of-care carboplatin/paclitaxel (C/T) as first-line systemic therapy for patients with advanced/recurrent endometrial cancer. METHODS: We designed a Markov model to simulate treatment outcomes for advanced/recurrent endometrial cancer patients whose tumors are either microsatellite stable (MSS) or have high microsatellite instability (MSI-high). We adopted a healthcare sector perspective for the analysis. Model inputs for costs, health utility, and clinical estimates were obtained from the literature including data from GOG0209 and KEYNOTE-146. Primary outcomes included costs of care, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). The time-horizon was three years and the discount rate was 3% annually. RESULTS: In a MSS cohort, compared to C/T, first-line treatment with P/L increased treatment costs by $212,670 and decreased QALYs by 0.28 per patient. In a MSI-high cohort, compared to C/T, P/L increased costs by $313,487 and increased QALYs by 0.11 per patient, representing an ICER of $2,849,882 per QALY. Sensitivity analyses found that the price of the new drugs was the most important determinant of the ICER and that the price of the new drugs would need to decrease by 85% to $2817 per cycle to reach a $150,000/QALY threshold. CONCLUSION: In the MSS model, we found that first-line therapy for advanced or recurrent endometrial cancer with P/L increased costs and worsened outcomes compared to C/T. In the MSI-high model, P/L improved survival and QALYs compared to C/T but was not cost-effective at the current cost of the drugs.

Association Between First-Line Immune Checkpoint Inhibition and Survival for Medicare-Insured Patients With Advanced Non-Small Cell Lung Cancer.

Importance: Immunotherapy is now a cornerstone of treatment for advanced non-small cell lung cancer (NSCLC), but its uptake and effectiveness among older patients outside clinical trials remain poorly understood. Objective: To understand treatment patterns and evaluate the overall survival associated with checkpoint inhibitor immunotherapy, cytotoxic chemotherapy, and combined chemoimmunotherapy for older patients who have advanced NSCLC and Medicare coverage. Design, Setting, and Participants: This retrospective cohort study included Medicare-insured patients in the US aged 66 to 89 years who initiated first palliative-intent systemic therapy for lung cancer between January 1, 2016, and December 31, 2018. Survival follow-up continued through March 31, 2020. A total of 19 529 patients who had advanced lung cancer and were insured by a Medicare fee-for-service plan were included in the analysis. Exposures: Regimens included pembrolizumab monotherapy (n = 3079), combined platinum-based drug (ie, cisplatin or carboplatin [hereinafter, platinum]) and pemetrexed disodium (n = 5159), combined platinum and a taxane (ie, paclitaxel, nab-paclitaxel, or docetaxel) (n = 9866), and combined platinum, pemetrexed, and pembrolizumab (n = 1425), as ascertained using Medicare claims from the Centers for Medicare & Medicaid Services. Main Outcomes and Measures: The primary outcome was overall survival, which was measured using the restricted mean survival time (RMST) with propensity score adjustment for clinical and sociodemographic characteristics. Median survival was also reported for comparison with outcomes from registrational trials. Results: A total of 19 529 patients (54% male, 46% female; median age, 73.8 [interquartile range, 69.9-78.4] years) were identified for analysis. The uptake of pembrolizumab-containing regimens in the Medicare population was rapid, increasing from 0.7% of first-line treatments in the second quarter of 2016 to 42.4% in the third quarter of 2018. Patients who were older (≥70 years, 2484 [81%]), were female (1577 [51%]), and/or had higher Risk Stratification Index scores (highest quintile, 922 [30%]) were more likely to receive single-agent pembrolizumab than chemotherapy. After propensity score adjustment, pembrolizumab was associated with survival similar to platinum/pemetrexed (RMST difference, -0.2 [95% CI, -0.5 to 0.2] months) or platinum/taxane (RMST difference, -0.7 [95% CI, -1.0 to -0.4] months). Patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy also had adjusted survival similar to those receiving platinum/pemetrexed chemotherapy (RMST difference, 0.5 [95% CI, 0.1-0.9] months). The unadjusted median survival was 11.4 (95% CI, 10.5-12.3) months among patients receiving single-agent pembrolizumab, approximately 15 months shorter than observed among pembrolizumab-treated participants in the KEYNOTE-024 trial. The unadjusted median survival was 12.9 (95% CI, 11.8-14.0) months among patients receiving platinum/pemetrexed/pembrolizumab chemoimmunotherapy, approximately 10 months shorter than observed among platinum/pemetrexed/pembrolizumab-treated participants in the KEYNOTE-189 trial. Conclusions and Relevance: Immunotherapy has been incorporated rapidly into treatment for patients with advanced NSCLC. However, survival estimates in the Medicare population are much shorter than those reported in registrational trials. These results provide contemporary estimates of survival for older patients with advanced NSCLC treated in routine practice, facilitating patient-centered decision-making.

First-line atezolizumab plus chemotherapy in advanced non-squamous non-small cell lung cancer: a cost-effectiveness analysis from China.

Objective: To assess the cost-effectiveness of atezolizumab in combination with carboplatin plus nab-paclitaxel-based chemotherapy versus chemotherapy alone for first-line treatment of advanced non-squamous non-small cell lung cancer (NSCLC) from the Chinese healthcare system perspective.Methods: A Markov model was developed based on the IMpower130 clinical trial. Drug costs and health state utility were obtained from the literature. Outcomes included life-years (LYs), quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty.Results: When compared to chemotherapy alone, atezolizumab plus chemotherapy provides an additional 0.34 LY and 0.19 QALY, and has an ICER of $180,560.15 per additional LY gained and that of $325,328.71 per QALY gained. Sensitivity analysis revealed that the results were most sensitive to changes in atezolizumab cost. Probabilistic sensitivity analysis showed that there was a 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay values of $30,828 per QALY. If the WTP threshold increased to $325,000 per QALY, atezolizumab plus chemotherapy has a 50% chance to be cost-effective.Conclusions: From the Chinese healthcare system perspective, atezolizumab combination is not cost-effective for first-line therapy of advanced non-squamous NSCLC.

Trastuzumab with carboplatin/paclitaxel for treatment of advanced stage and recurrent uterine papillary serous carcinoma: A cost-effectiveness analysis.

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is a variant of endometrial cancer that is aggressive and associated with poor outcomes. We sought to evaluate the cost effectiveness of carboplatin/paclitaxel alone versus carboplatin/paclitaxel with trastuzumab among patients with Her2/neu-positive advanced or recurrent UPSC. METHODS: We designed a Markov model in TreeAge Pro 2019 software to simulate management of a theoretical cohort of 4000 patients with Her2/neu-positive advanced or recurrent uterine papillary serous carcinoma (UPSC) followed for four years. In the carboplatin/paclitaxel with trastuzumab strategy, we included the cost of testing for Her2/neu status. We obtained all model inputs from the literature and a societal perspective was assumed. Outcomes included progression-free survival, progression, UPSC-specific mortality, cost, and quality-adjusted life years (QALYs). The intervention was considered cost effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were used to determine the robustness of the results. RESULTS: In our theoretical cohort of 4000 women, treatment with the addition of trastuzumab resulted in 637 fewer deaths and 627 fewer cases of progression compared with treatment with carboplatin/paclitaxel alone. Treatment with trastuzumab was associated with an additional cost of $144,335,895, but was associated with an increase of 2065 QALYs. The ICER was $69,903 per QALY, which was below our willingness-to-pay threshold. Sensitivity analysis demonstrated that this treatment strategy was cost-effective until the cost of 6 months of treatment surpassed $38,505 (baseline input: $27,562). CONCLUSION: We found that the addition of trastuzumab to carboplatin/paclitaxel was a cost-effective treatment strategy for patients with advanced/recurrent Her2/neu-positive UPSC.