Evaluation of Metronomic Therapy as a Low-Cost, Sustainable, Standard-of-Care Option in Desmoid Fibromatosis: Real-World Data From a Tertiary Care Center in India.

PURPOSE: Desmoid fibromatosis (DF) is a locally aggressive tumor with low mortality but significant morbidity. There is a lack of standard of care, and existing therapies are associated with significant barriers including access, cost, and toxicities. This study aimed to explore the efficacy and safety of the metronomic therapy (MT) in DF in a large, homogenous cohort from India. PATIENTS AND METHODS: This study involved histologically confirmed DF cases treated with MT comprising vinblastine (6 mg) and methotrexate (15 mg) both once a week, and tamoxifen (40 mg/m2) in two divided doses once daily between 2002 and 2018. RESULTS: There were 315 patients with a median age of 27 years; the commonest site was extremity (142 of 315; 45.0%). There were 159 (50.1%) male patients. Of the 123 (39.0%) prior treated patients, 119 had surgery. Of 315 patients, 263 (83.5%) received treatment at our institute (MT-151, 77-local treatment, 9-tyrosine kinase inhibitor, and 26 were observed). Among the MT cohort (n = 163, 61.2%), at a median follow-up of 36 (0.5-186) months, the 3-year progression-free and overall survival were 81.1% (95% CI, 74.3 to 88.4) and 99.2% (95% CI, 97.6 to 100), respectively. There were 35% partial responses. Ninety-two patients (56.4%) completed 1-year therapy, which was an independent prognosticator (P < .0001; hazard ratio, 0.177 [95% CI, 0.083 to 0.377]). MT was well tolerated. Predominant grade ≥3 toxicities were febrile neutropenia, 12 (7.4%) without any chemotoxicity-related death. The annual cost of MT was $130 US dollars. CONCLUSION: The novel, low-cost MT qualifies as one of the effective, less toxic, sustainable, standard-of-care options for the treatment of DF with global reach and merits wide recognition.

Cost-utility of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of advanced gastric or gastroesophageal junction cancer in China.

OBJECTIVES: ORIENT-16, a phase III clinical trial conducted at 62 hospitals in China, reported that add-on sintilimab (Sin) to chemotherapy (Chemo) had favorable efficacy (p < 0.05) for patients with advanced HER2-negative gastric or gastroesophageal junction cancer (GC/GEJC). This study aimed to evaluate the cost-utility of the Sin+Chemo based on results of ORIENT-16 from the perspective of Chinese healthcare payers. METHODS: A three-state partitioned survival model was developed to simulate the 10-year life expectancy and total healthcare costs for patients with advanced HER2-negative GC/GEJC. Primary measure outcomes were: cost, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs). Sensitivity/scenario analyses were conducted to assess the model robustness. RESULTS: In all patients, Sin+Chemo vs Chemo increased costs by $6,472, additionally providing 0.61 QALYs, resulting in an ICUR of $10,610/QALY. While, in PD-L1 combined positive score ≥ 5 cohort, the ICUR was $9,738/QALYs. The ICUR was most sensitive to the utility of progression-free survival. The probabilistic sensitivity analysis showed that add-on Sin had a 100% probability of being cost-effective at a willingness-to-pay threshold of $18,625/QALY gained. CONCLUSIONS: Sin+Chemo is a cost-effective first-line treatment option for advanced HER2-negative GC/GEJC in China. CLINICAL TRIAL REGISTRATION: ORIENT-16, www.clinicaltrials.gov, identifier is NCT03745170.

Economic value of toripalimab plus axitinib as first-line treatment for advanced renal cell carcinoma in China: a model-based cost-effectiveness analysis.

OBJECTIVE: The current analysis aimed to evaluate the economic benefit of toripalimab plus axitinib for previously untreated RCC patients from the Chinese healthcare system perspective. METHODS: The partitioned survival model was developed to simulate 3-week patients' transition in 20-year time horizon to evaluate the cost-effectiveness of toripalimab plus axitinib compared with sunitinib for advanced RCC. Survival data were gathered from the RENOTORCH trial, and cost and utility inputs were obtained from the database and published literature. Total cost, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outputs. Subgroup analyses and sensitivity analyses were conducted to increase the comprehensiveness and estimate the robustness of the model results. RESULTS: In the base-case analysis, compared with sunitinib, toripalimab plus axitinib could bring additional 1.19 LYs and 0.65 QALYs, with the marginal cost of $41,499.23, resulting in the ICER of $64,337.49/QALY, which is higher than the WTP threshold. And ICERs were always beyond the WTP threshold of all subgroups. Sensitivity analyses demonstrated the model results were robust. CONCLUSIONS: Toripalimab plus axitinib was unlikely to be the cost-effective first-line therapy for patients with previously untreated advanced RCC compared with sunitinib from the Chinese healthcare system perspective.

Assessment of Capecitabine and Bevacizumab With or Without Atezolizumab for the Treatment of Refractory Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: Cotargeting vascular endothelial growth factor and programmed cell death 1 or programmed cell death ligand 1 may produce anticancer activity in refractory metastatic colorectal cancer (mCRC). The clinical benefit of atezolizumab combined with chemotherapy and bevacizumab remains unclear for the treatment of mCRC. Objectives: To assess whether the addition of atezolizumab to capecitabine and bevacizumab therapy improves progression-free survival (PFS) among patients with refractory mCRC and to perform exploratory analyses among patients with microsatellite-stable (MSS) disease and liver metastasis. Design, Setting, and Participants: This double-blind phase 2 randomized clinical trial enrolled 133 patients between September 25, 2017, and June 28, 2018 (median duration of follow-up for PFS, 20.9 months), with data cutoff on May 4, 2020. The study was conducted at multiple centers through the Academic and Community Cancer Research United network. Adult patients with mCRC who experienced disease progression while receiving fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and anti-epidermal growth factor receptor antibody therapy (if the patient had a RAS wild-type tumor) were included. Interventions: Patients were randomized (2:1) to receive capecitabine (850 or 1000 mg/m2) twice daily on days 1 to 14 and bevacizumab (7.5 mg/kg) on day 1 plus either atezolizumab (1200 mg; investigational group) or placebo (placebo group) on day 1 of each 21-day cycle. Main Outcomes and Measures: The primary end point was PFS; 110 events were required to detect a hazard ratio (HR) of 0.65 with 80% power (1-sided α = .10). Secondary end points were objective response rate, overall survival (OS), and toxic effects. Results: Of 133 randomized patients, 128 individuals (median age, 58.0 years [IQR, 51.0-65.0 years]; 77 men [60.2%]) were assessed for efficacy (82 in the investigational group and 46 in the placebo group). Overall, 15 patients (11.7%) self-identified as African American or Black, 8 (6.3%) as Asian, 1 (0.8%) as Pacific Islander, 101 (78.9%) as White, 1 (0.8%) as multiple races (Asian, Native Hawaiian/Pacific Islander, and White), and 2 (1.6%) as unknown race or unsure of race. Microsatellite-stable disease was present in 110 patients (69 in the investigational group and 41 in the placebo group). Median PFS was 4.4 months (95% CI, 4.1-6.4 months) in the investigational group and 3.6 months (95% CI, 2.2-6.2 months) in the placebo group (1-sided log-rank P = .07, a statistically significant result; HR, 0.75; 95% CI, 0.52-1.09). Among patients with MSS and proficient mismatch repair, the HR for PFS was 0.66 (95% CI, 0.44-0.99). The most common grade 3 or higher treatment-related adverse events in the investigational vs placebo groups were hypertension (6 patients [7.0%] vs 2 patients [4.3%]), diarrhea (6 patients [7.0%] vs 2 patients [4.3%]), and hand-foot syndrome (6 patients [7.0%] vs 2 patients [4.3%]). One treatment-related death occurred in the investigational group. In the investigational group, the response rate was higher among patients without liver metastasis (3 of 13 individuals [23.1%]) vs with liver metastasis (4 of 69 individuals [5.8%]). The benefit of atezolizumab for PFS and OS was greater among patients without vs with liver metastasis (primary analysis of PFS: HR, 0.63 [95% CI, 0.27-1.47] vs 0.77 [95% CI, 0.51-1.17]; OS: HR, 0.33 [95% CI, 0.11-1.02] vs 1.14 [95% CI, 0.72-1.81]). Conclusions and Relevance: In this randomized clinical trial, the addition of atezolizumab to capecitabine and bevacizumab therapy provided limited (ie, not clinically meaningful) clinical benefit. Patients with MSS and proficient mismatch repair tumors and those without liver metastasis benefited more from dual inhibition of the vascular endothelial growth factor and programmed cell death 1 or programmed cell death ligand 1 pathways. Trial Registration: ClinicalTrials.gov Identifier: NCT02873195.

The epidemiology, treatment patterns, healthcare utilizations and costs of Acute Myeloid Leukaemia (AML) in Taiwan.

BACKGROUNDS: An increasing incidence of Acute Myeloid Leukaemia (AML) has been reported in several Western countries. However, the epidemiology of AML in Asia is very limited. According to the National Comprehensive Cancer Network (NCCN) guideline of AML, a range of conventional therapy options is available to AML patients. Nevertheless, different treatment strategies may result in diverse healthcare utilization and costs. Understanding the treatment patterns, healthcare utilization and costs of AML would thus be essential for clinicians and policymakers to optimize the treatment strategies of AML. OBJECTIVES: The objective of this study was to investigate the incidence, treatment patterns, healthcare utilization and costs of AML in Taiwan using a nationwide population database. METHODS: We retrospectively identified AML patients diagnosed from 2006 to 2015 from the Taiwan Cancer Registry Database (TCRD) and estimated the epidemiology of AML in Taiwan. The TCRD was linked to National Health Insurance Research Database (NHIRD) to collect the treatment patterns and health care utilization. Patients diagnosed with AML from 2011 to 2015 were further identified to analyze treatment patterns, healthcare utilization and costs. RESULTS: The crude annual incidence of AML increased from 2.78 to 3.21 cases per 100,000 individuals from 2006 to 2015. However, the age-standardized rate (ASRs) of AML slightly declined from 2.47 to 2.41 cases per 100,000 individuals in the same period. Among 2,179 AML patients who received induction therapy (median age: 56 years), most of them (n = 1744; 80.04%) received standard-dose cytarabine (SDAC) regimen. The remaining 162 patients received high dose cytarabine (HDAC) and 273 patients received non-standard dose cytarabine (N-SDAC) regimen as the induction therapy. The median medical costs in our study for patients treated with chemotherapy alone was $42,271 for HDAC, $36,199 for SDAC and $36,250 for N-SDAC. For those who received hematopoietic stem cell transplantation (HSCT) after induction therapy, their median medical costs were $78,876 for HDAC, $78,593 for SDAC and $79,776 for N-SDAC. CONCLUSIONS: This study is the first population-based study conducted in Asia to provide updated and comprehensive information on epidemiology, treatment patterns and healthcare resource utilization and costs of AML.

Cost-effectiveness analysis of pressurized intraperitoneal aerosol chemotherapy (PIPAC) in patients with gastric cancer and peritoneal metastasis.

OBJECTIVE: The aim of this study was to assess the cost-effectiveness of pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) for the treatment of advanced gastric cancer. METHODS: A Partitioned Survival Model followed by state transition Markov model was developed to estimate the costs and effectiveness of the use of PIPAC C/D versus palliative chemotherapy in the UK. The intervention was assessed at two different levels of care, including upfront therapy (PIPAC C/D plus Oxaliplatin in combination with Capecitabine (XELOX) chemotherapy versus first-line chemotherapy alone) and second-line therapy (PIPAC C/D alone versus second-line chemotherapy (ramucirumab monotherapy)). Data from multiple sources, including published literature and UK-based databases, were used to inform the economic model. RESULTS: For the upfront therapy analysis, the estimated total costs in the intervention and comparator arms were £32,606 (SD: £3877) and £17,844 (SD: £920), respectively. PIPAC C/D plus XELOX led to an increase of 0.46 in quality-adjusted life-years (QALYs) gained. The incremental cost per QALY gained was £31,868. For the second-line therapy analysis, the use of PIPAC C/D led to an increase of 0.19 in QALYs and a £21,474 reduction in costs, meaning the intervention was a dominant strategy. CONCLUSIONS: The cost-effectiveness results for the upfront therapy analysis indicate that PIPAC C/D plus chemotherapy is a cost-effective strategy. Additionally, PIPAC C/D alone as a second-line therapy has the potential to reduce costs and improve clinical outcomes for patients with advanced gastric cancer with peritoneal metastasis.

Effects of Goshajinkigan (TJ-107) for oxaliplatin-induced peripheral neurotoxicity using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire in a Phase II, multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: The aim of the present study was to evaluate the efficacy of TJ-107 for oxaliplatin-induced peripheral neurotoxicity in prospective, multi-institutional, randomized, double-blind, placebo-controlled Phase II trials using the functional assessment of cancer therapy/gynecologic oncology group 12-item neurotoxicity questionnaire (FACT-GOG-NTX-12). PATIENTS AND METHODS: The patients who were registered to the Goshajinkigan oxaliplatin neurotoxicity evaluation study (UMIN000002211) were analyzed. A NTX-12 from the validated FACT/GOG-NTX-12 was assessed before treatment and at the end of every 2 cycles. RESULTS: The comparisons of the median scores for TJ-107 and the placebo at 8 and 26 weeks were as follows: numbness or tingling in the hands (P = 0.5820), numbness or tingling in the feet (P = 0.3236), feeling of discomfort in the hands (P = 0.8219), feeling of discomfort in the feet (P = 0.5361), joint pain or muscle cramps (P = 0.1974), feeling weak all over (P = 0.2771), trouble hearing (P = 0.2832), ringing or buzzing in ears (P = 0.1031), trouble buttoning buttons (P = 0.1653), trouble feeling the shape of small objects when held in hand (P = 0.2919), trouble walking (P = 0.5406), and pain in the hands or feet when exposed to cold temperatures (P = 0.1872). CONCLUSION: There might be no clinically significant difference between the use of TJ-107 and the severity and quality of life for patients treated with oxaliplatin.

Clinical Benefit of Therapeutic Drug Monitoring in Colorectal Cancer Patients Who Received Fluorouracil-Based Chemotherapy.

BACKGROUND The impact of therapeutic drug management (TDM) on reducing toxicity and improving efficacy in colorectal cancer (CRC) patients receiving fluorouracil-based chemotherapy is still unclear. MATERIAL AND METHODS A total of 207 patients (Study Group n=54, Historical Group n=153) with metastatic colorectal cancer were enrolled. All of them received 6 administrations of the 5-FU based regimens. Initial 5-FU dosing of all patients was calculated using body surface area (BSA). In the Study Group, individual exposure during each cycle was measured using a nanoparticle immunoassay, and the 5-FU blood concentration was calculated using the area under the curve (AUC). We adjusted the 5-FU infusion dose of the next cycle based on the AUC data of the previous cycle to achieve the target of 20-30 mg×h/L. RESULTS In the fourth cycle, patients in the target concentration range (AUC mean, 26.3 mg×h/L; Median, 28 mg×h/L; Range, 14-38 mg×h/L; CV, 22.4%) accounted for 46.8% of all patients, which were more than the ones in the first cycle (P<0.001). 5-FU TDM significantly reduced the toxicity of chemotherapy and improved its efficacy. The Study Group (30/289) showed a lower percentage of severe adverse events than that in the Historical Group (185/447) (P<0.001). The incidences of complete response and partial response in the Study Group were higher than those in the Historical Group (P=0.032). CONCLUSIONS TDM in colorectal cancer can reduce toxicity, improve efficacy and clinical outcome, and can be routinely used in 5-FU-based chemotherapy.

Minimal residual disease assessment by multiparameter flow cytometry in transplant-eligible myeloma in the EMN02/HOVON 95 MM trial.

Minimal residual disease (MRD) by multiparameter flow cytometry (MFC) is the most effective tool to define a deep response in multiple myeloma (MM). We conducted an MRD correlative study of the EMN02/HO95 MM phase III trial in newly diagnosed MM patients achieving a suspected complete response before maintenance and every 6 months during maintenance. Patients received high-dose melphalan (HDM) versus bortezomib-melphalan-prednisone (VMP) intensification, followed by bortezomib-lenalidomide-dexamethasone (VRd) versus no consolidation, and lenalidomide maintenance. Bone marrow (BM) samples were processed in three European laboratories, applying EuroFlow-based MFC protocols (eight colors, two tubes) with 10-4-10-5 sensitivity. At enrollment in the MRD correlative study, 76% (244/321) of patients were MRD-negative. In the intention-to-treat analysis, after a median follow-up of 75 months, 5-year progression-free survival was 66% in MRD-negative versus 31% in MRD-positive patients (HR 0.39; p < 0.001), 5-year overall survival was 86% versus 69%, respectively (HR 0.41; p < 0.001). MRD negativity was associated with reduced risk of progression or death in all subgroups, including ISS-III (HR 0.37) and high-risk fluorescence in situ hybridization (FISH) patients (HR 0.38;). In the 1-year maintenance MRD population, 42% of MRD-positive patients at pre-maintenance became MRD-negative after lenalidomide exposure. In conclusion, MRD by MFC is a strong prognostic factor. Lenalidomide maintenance further improved MRD-negativity rate.

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 cost-effectiveness of atezolizumab in first-line for metastatic triple negative breast cancer is heavily linked to PD-L1 level.

The present analysis was conducted to assess the pharmacological costs of atezolizumab as first-line treatment in triple negative metastatic breast cancer (mBC). Pivotal phase III randomized controlled trial (RCT) was considered. Nine hundred and two patients were included. Differences in costs between the 2 arms (atezolizumab plus nabpaclitaxel versus placebo plus nab-paclitaxel) was 17 398 €, with a cost of 7564 €per month of OS-gain in the overall population and 2485 €per month of OS-gain in PD-L1-positive (≥1) population. Combining pharmacological costs of drugs with the measure of efficacy represented by the OS, atezolizumab could be considered cost-effective in first-line treatment for triple-negative mBC only in PD-L1-positive population, but a reduction of costs is mandatory.

Phase II study of trifluridine/tipiracil (TAS-102) therapy in elderly patients with colorectal cancer (T-CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers.

PURPOSE: The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. METHODS: This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1-5 and 8-12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. RESULTS: A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9-4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7-8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). DISCUSSION: The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. TRIAL REGISTRATION NUMBER: UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network).

Cost-effectiveness Analysis of Atezolizumab Plus Nab-Paclitaxel for Advanced PD-L1 Positive Triple-Negative Breast Cancer in Japan.

BACKGROUND AND OBJECTIVES: Atezolizumab is an anti-programmed death ligand 1 (PD-L1) antibody that shows good safety and efficacy for patients with PD-L1-positive triple-negative breast cancer (TNBC). The cost of atezolizumab therapy is expensive, and its economic burden is an important problem. In this study, we evaluated the cost effectiveness of atezolizumab plus nab-paclitaxel therapy (AnP) compared with nab-paclitaxel monotherapy (nP) for PD-L1-positive TNBC under Japanese medical conditions and environments using a Markov model. METHODS: The medical information was collected from data published by the IMpassion130 trial. A Markov model was established to simulate the number of patients in each disease state after AnP or nP therapy during each time period. As indices for cost effectiveness, total cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICER) were calculated. Probabilistic sensitivity analysis (PSA) was used to assess the uncertainty of the model using 10,000 Monte Carlo simulations with difference parameters. RESULTS: The QALYs for AnP treatment were longer than for nP treatment (1.12 vs 0.82 QALYs), but the total cost of AnP treatment was more expensive than that of nP treatment (¥11,070,143 vs ¥2,056,164). The ICER values comparing AnP treatment with nP treatment were ¥30,208,143/QALY. The ICER/QALY was more expensive than the willingness-to-pay (WTP) of ¥15,000,000 per QALY. To achieve a 50% cost-effective probability with a WTP threshold, the price of the atezolizumab should be reduced by 55.1%. CONCLUSIONS: AnP was not cost effective compared to nP for PD-L1-positive inoperable TNBC under the Japanese condition.

Cost-effectiveness of ribociclib plus endocrine therapy versus placebo plus endocrine therapy in HR-positive, HER2-negative breast cancer.

BACKGROUND: The 2015 American Society of Clinical Oncology guidelines recommend first-line treatment of hormone receptor (HR)-positive breast cancer with endocrine therapy plus or minus palbociclib, a selective cyclin-dependent kinase (CDK)4/6 inhibitor. In 2018, the U.S. Food and Drug Administration approved ribociclib, a new orally available selective CDK4/6 inhibitor. While gains in progression-free survival (PFS) and overall survival (OS) from ribociclib are important for clinical and treatment outcomes, trade-offs in adverse events (AEs) and additional costs necessitate cost-effectiveness analysis (CEA) to assist consideration by third-party payer systems, physicians, and patients. OBJECTIVES: To (a) develop a Markov model and (b) determine the cost-effectiveness of ribociclib plus endocrine therapy versus endocrine therapy alone as treatment for premenopausal and perimenopausal patients with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. METHODS: A lifetime 3-state Markov model ("stable," "progressed," and "dead" health states) was developed using a U.S. payer perspective. Transition probabilities were calculated based on OS and PFS outcomes from the randomized controlled phase 3 trial MONALEESA-7. These Kaplan-Meier curves were extended to lifetime by estimating best-fit distributions using loglogistic distribution for ribociclib curves and Weibull distribution for placebo curves. Costs were obtained from national data sources using 2019 U.S. dollars (USD) and discounted by 3%. Utilities were obtained via published breast cancer literature and were included for each health state and for time spent with each AE. Results were expressed as an incremental cost-effectiveness ratio (ICER) expressed as USD per quality-adjusted life-year (QALY) saved. Treatments were assumed to be cost-effective based on a willingness-to-pay (WTP) threshold of $150,000 per QALY gained. Base-case, 1-way sensitivity tornado diagrams and probabilistic sensitivity analyses demonstrated changes in the ICER and were driven by the cost of ribociclib and the utility of remaining in the stable health state. RESULTS: Ribociclib plus endocrine therapy was cost-effective at an ICER of $124,513 per QALY when compared with endocrine therapy alone at a WTP threshold of $150,000. The ribociclib plus endocrine therapy arm had an effectiveness of 5.28 QALYs and a total cost of $385,112, while placebo plus endocrine therapy provided only 2.46 QALYs at a lower total cost of $67.246. The model was sensitive to the cost of ribociclib and the utility of time spent in the stable health state. Probabilistic sensitivity analysis demonstrated that endocrine therapy alone was cost-effective until a WTP of $125,000 and was cost-effective 72% of the time at the WTP threshold. CONCLUSIONS: Ribociclib plus endocrine therapy is more cost-effective than endocrine therapy alone. Professionals in managed care settings should consider the pharmacoeconomic benefits of ribociclib for the treatment of HR-positive, HER2-negative breast cancer as they make value-based formulary decisions. Further CEAs should be considered as direct treatment comparison trials between CDK4/6 inhibitors are completed in the future. DISCLOSURES: No outside funding supported this study. The authors have nothing to disclose.

The challenge of value-based pricing in combination therapy: the case of trastuzumab and pertuzumab in HER2+ metastatic breast cancer.

BACKGROUND: Under current reimbursement (CR) practice even though an add-on drug in a combination therapy may produce marginal value in terms of health gain, the original therapy may also share in the reward for this additional value. We examine an alternative 'marginal value-based reimbursement' (MVBR) model in which an original therapy would not share in the marginal value. METHODS: In a case study for treatment of HER2+ metastatic breast cancer, we computed the incremental cost-effectiveness ratios (ICERs) of adding pertuzumab to trastuzumab and docetaxel (PHT) vs. trastuzumab and docetaxel (HT) under the CR and the MVBR models, respectively. We further estimated the revised cost of pertuzumab under three alternative willingness-to-pay thresholds based on (a) using the current ICER of PHT vs. HT, (b) the historical ICER of HT vs. docetaxel, and (c) applying the oft-used $150,000/quality-adjusted life year (QALY) gained. RESULTS: If reimbursement were changed from CR to MVBR, at the current price of pertuzumab, the ICER would decline from $409,213 to $323,236/QALY gained. If the price were adjusted under the three thresholds, the payment for pertuzumab would be increased by between 32% and 93%. CONCLUSION: The proposed MVBR model would provide a stronger economic incentive to develop add-on drugs.

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.

A Non-Surgical and Cost-Effective Treatment Approach Employing Topical Imiquimod, 5-Fluorouracil, and Tretinoin for Primary Non-Melanoma Skin Cancers.

BACKGROUND: Minimally invasive alternative approaches to treat non-melanoma skin cancers remain limited and unproven. OBJECTIVE: We aim to assess the efficacy of varying combinations of anti-tumor agents—imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream—with brief cryotherapy in treating non-melanoma skin cancers. METHODS: This retrospective study included 690 cases of non-melanoma skin cancers in 480 patients who received a diagnosis of a basal cell carcinoma or squamous cell carcinoma during a ten-year period. During treatment period, patients applied 30 applications of one of three combinations (imiquimod/tretinoin, 5-fluorouracil/tretinoin, or imiquimod/5-fluorouracil/tretinoin) and had cryotherapy every 2 weeks. Each patient had a clinical examination at least three years post-treatment or documented treatment failure. Clearance was defined by a lack of persistence or recurrence for 3 years following the completion of treatment. The likelihood of lesion clearance was evaluated using multivariable logistic regression analysis. RESULTS: A total of 186 cases (97; basal cell carcinoma and 89; squamous cell carcinoma) in 133 patients [37% women and 63% men; median (interquartile range) age, 77 (69, 83) years] met the inclusion criteria. Multivariable logistic regression analysis adjusting for clinical and lesion variables demonstrated that, relative to the imiquimod/5-fluorouracil/tretinoin treatment approach, imiquimod/ tretinoin (odds ratio, 0.05; 95% confidence interval, 0.00-0.99) and 5-fluorouracil/tretinoin (0.02; 0.00–0.45) were associated with lower likelihoods of lesion clearance. Likewise, morpheaform basal cell carcinoma had a lower probability of clearance (0.05; 0.00–0.72). CONCLUSIONS: The combination of imiquimod/5-fluorouracil/tretinoin with cryotherapy had high clearance rates and was the most effective treatment regimen. J Drugs Dermatol. 2021;20(3):260-267. doi:10.36849/JDD.5427.

The impacts of race and regimens on the efficacy and safety of paclitaxel and platinum combination treatment for patients with advanced non-small cell lung cancer.

PURPOSE: Paclitaxel-platinum chemotherapy is the first-line treatment for advanced non-small cell lung cancer (NSCLC) patients. This study quantitatively evaluated the factors influencing the efficacy and safety of the paclitaxel-platinum regimen to provide the necessary reference for the development of clinical practice and clinical trials. METHODS: A literature search was performed using public databases. The parametric survival function was used to analyze the overall survival (OS) time course of patients treated with the paclitaxel-platinum regimen. The random effects model in the single-arm meta-analysis was used to analyze the objective response rate (ORR) and the incidence of grade 3-4 adverse events (AEs) under the predefined subgroups according to race and the regimen. RESULTS: A total of 31 studies consisting of 3365 participants were included in the analysis. Race was the most important determinant of efficacy and safety in the paclitaxel-platinum regimen, with the median survival time and ORR in East Asians and non-East Asians being 12.2 months (95% CI: 10.5-14.4 months) and 37% (95% CI: 32-41%) and 8.4 months (95% CI: 6.5-11.0 months) and 28% (95% CI: 25-32%), respectively. The incidence of grade 3-4 AEs such as leukopenia and neutropenia was about three times higher in East Asians compared to non-East Asians. CONCLUSIONS: The efficacy and safety of the paclitaxel-platinum regimen can vary between East Asian and non-East Asian populations and between different treatment schedules. The results of this study can provide a reliable and precise external control for the future evaluation of new treatment options for advanced NSCLC.

Neoadjuvant therapy for pancreatic cancer: Limitations and advances of response assessment (Review).

Neoadjuvant therapy (NAT) has been widely recommended for managing patients with borderline resectable pancreatic cancer and resectable tumors with high risk factors. Accurate evaluation of the response after NAT is crucial to decide surgery, which then improves the rate of R0 resection and avoids meaningless surgery. The response to NAT is currently evaluated by conventional radiological examination and changes of serum CA19­9 levels. However, these assessments cannot accurately reflect the response to NAT. This article describes the limitations and advances of NAT response evaluation in pancreatic cancer. The values of some traditional imaging techniques, including positron emission tomography, endoscopic ultrasound, and diffusion weighted magnetic resonance imaging, are discussed, as well as novel imaging modalities or biomarkers, such as radiomics, dual energy computed tomography and liquid biopsy.

Burden of Treatment-Induced Peripheral Neuropathy in Patients with Multiple Myeloma in Sweden.

INTRODUCTION: Treatment-induced peripheral neuropathy (TIPN) is a complication of multiple myeloma (MM) treatment. OBJECTIVE: This real-world, retrospective study used electronic medical record (EMR) data from 3 Swedish clinics to assess the occurrence and economic burden of TIPN in patients with MM. METHODS: Eligible patients had an MM diagnosis in the Swedish Cancer Registry between 2006 and 2015 and initiated treatment during that period. Follow-up was until last EMR visit, death, or study end (April 2017). The current analyses included patients receiving bortezomib, lenalidomide, carfilzomib, or thalidomide at any treatment line. To discern healthcare resource utilization (HCRU) and costs associated with TIPN from other causes, patients with TIPN were matched with those without on baseline characteristics, treatment, and line of therapy. All analyses were descriptive. RESULTS: Overall, 457 patients were included; 102 (22%) experienced TIPN. Patients experiencing TIPN during first-line treatment mostly received bortezomib-based regimens (n = 48/57 [84%]); those with TIPN during second- and third/fourth-line treatment mostly received lenalidomide/thalidomide-based regimens (19/31 [61%], 8/14 [57%], respectively). Patients with TIPN had higher HCRU/costs than those without TIPN (mean differences in hospital outpatient visits: 5.2, p = 0.0031; total costs per patient-year: EUR 17,183, p = 0.0007). CONCLUSIONS: Effective MM treatments associated with a reduced incidence of TIPN could result in decreased healthcare expenditure.