Per Progression-free Life-year Saved Research Articles

Cost-effectiveness of Maintenance Therapy Based on Molecular Classification Following Treatment of Primary Epithelial Ovarian Cancer in the United States

There are large randomized clinical trials-SOLO-1 (Olaparib Maintenance Monotherapy in Patients With BRCA Mutated Ovarian Cancer Following First Line Platinum Based Chemotherapy [December 2018]), PRIMA (A Study of Niraparib Maintenance Treatment in Patients With Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy [September 2019]), and PAOLA-1 (Platine, Avastin and Olaparib in 1st Line [December 2019])-reporting positive efficacy results for maintenance regimens for women with primary, advanced epithelial ovarian cancer. The findings resulted in approval by the US Food and Drug Administration of the treatments studied as of May 2020. However, there are pressing economic considerations given the many eligible patients and substantial associated costs. To evaluate the cost-effectiveness of maintenance strategies for patients with (1) a BRCA variant, (2) homologous recombination deficiency without a BRCA variant, or (3) homologous recombination proficiency. In this economic evaluation of the US health care sector using simulated patients with primary epithelial ovarian cancer, 3 decision trees were developed, one for each molecular signature. The maintenance strategies evaluated were olaparib (SOLO-1), olaparib-bevacizumab (PAOLA-1), bevacizumab (PAOLA-1), and niraparib (PRIMA). Base case 1 assessed olaparib, olaparib-bevacizumab, bevacizumab, and niraparib vs observation of a patient with a BRCA variant. Base case 2 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination deficiency without a BRCA variant. Base case 3 assessed olaparib-bevacizumab, bevacizumab, and niraparib vs observation in a patient with homologous recombination proficiency. The time horizon was 24 months. Costs were estimated from Medicare claims, wholesale acquisition prices, and published sources. Probabilistic sensitivity analyses with microsimulation were then conducted to account for uncertainty and assess model stability. One-way sensitivity analyses were also performed. The study was performed from January through June 2020. Incremental cost-effectiveness ratios (ICERs) in US dollars per progression-free life-year saved (PF-LYS). Assuming a willingness-to-pay threshold of $100 000/PF-LYS, none of the drugs could be considered cost-effective compared with observation. In the case of a patient with a BRCA variant, olaparib was the most cost-effective (ICER, $186 777/PF-LYS). The third-party payer price per month of olaparib would need to be reduced from approximately $17 000 to $9000 to be considered cost-effective. Olaparib-bevacizumab was the most cost-effective in the case of a patient with homologous recombination deficiency without a BRCA variant (ICER, $629 347/PF-LYS), and bevacizumab was the most cost-effective in the case of patient with homologous recombination proficiency (ICER, $557 865/PF-LYS). Even at a price of $0 per month, niraparib could not be considered cost-effective as a maintenance strategy for patients with homologous recombination proficiency. The findings of this study suggest that, at current costs, maintenance therapy for primary ovarian cancer is not cost-effective, regardless of molecular signature. For certain therapies, lowering the drug price alone may not make them cost-effective.

Cost-effectiveness of various maintenance therapies based on mutation status following first-line treatment of primary epithelial ovarian cancer in the United States.

e19399 Background: The recent SOLO1, PRIMA, and PAOLA trials all reported positive efficacy results, making it difficult to determine optimal upfront maintenance therapy for patients with primary, advanced ovarian cancer. We evaluated the cost-effectiveness of the maintenance strategies outlined in these trials for BRCA-positive patients, homologous-recombination deficient patients without a BRCA mutation (HRD-positive), and homologous-recombination proficient (HRD-negative) patients. Methods: Three decision analysis models were developed, one for each mutation status. We evaluated olaparib (SOLO1), olaparib/bevacizumab (PAOLA), bevacizumab alone (PAOLA), and niraparib (PRIMA) maintenance strategies. Base case 1 assessed olaparib vs olaparib/bevacizumab vs bevacizumab vs niraparib vs no maintenance therapy in BRCA-positive patients. Base cases 2 and 3 assessed olaparib/bevacizumab vs bevacizumab vs niraparib vs no maintenance therapy in HRD-positive and HRD-negative patients, respectively. Time horizon was 24 months. Costs, measured in U.S. dollars, were estimated from Medicare claims, wholesale acquisition prices, and previously published sources. Incremental cost-effectiveness ratios (ICERs) were in dollars per progression-free life-year saved (PF-LYS). One-way sensitivity analyses were performed varying drug cost and progression-free survival. Results: Assuming a willingness-to-pay threshold of $100,000/PF-LYS, none of the drug maintenance strategies could be considered cost effective compared with observation. In BRCA-positive patients (base case 1), olaparib monotherapy was the most cost-effective strategy, yielding an ICER of $181,059/PF-LYS. The third-party payer cost per 28-day supply of olaparib would need to be reduced from approximately $17,000 to $9,200 to be considered cost effective compared with observation. In HRD-positive patients (base case 2) and HRD-negative patients (base case 3), bevacizumab monotherapy was the most cost-effective option, with ICERs of $326,491/PF-LYS and $253,937/PF-LYS respectively. Conclusions: At current costs, maintenance therapy for primary ovarian cancer is not cost effective, regardless of mutation status. In BRCA-positive women, lowering the cost of olaparib may make it cost effective compared with observation.

795P - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy

BackgroundTrastuzumab plus chemotherapy is an effective therapy in HER2 positive advanced gastric cancer (AGC). However, the optimal maintenance treatment in patients benefited from the initial therapy remains unclear. MethodsThis was a prospective observational study in patients with untreated HER2 positive AGC. After 6 cycles of trastuzumab combined with chemotherapy, patients who had not progression disease were divided into two arms: trastuzumab monotherapy (arm A) and trastuzumab plus single chemo-agent derived from the initial chemotherapy (arm B). Patients received CT/MRI for response evaluation every 8 weeks or anytime suspected treatment failure. Adverse effects and costs were recorded every cycles. The primary end point was overall survival (OS), secondary end points included progression free survival (PFS), cost-effectiveness ratio per progression-free life-year saved (PF-LYS) and safety. ResultsIn total, 115 HER2 positive AGC treated with trastuzumab based first line chemotherapy were registered. After 6 cycles, 78 patients (6 CR, 46 PR, 26 SD) were eligible: 30 patients were in arm A accepted trastuzumab monotherapy as their maintenance therapy, 48 were in arm B. The clinicalpathological characteristics of two arms were well balanced. There was no significant differences of median OS (16.5 vs 20.0 months, P=0.169) or PFS (7.9 vs 11.0, P=0.892) between two arms. Adverse effects were also similar including cardiac safety. Subgroup analysis showed chemotherapy additional to trastuzumab benefited on OS in patients who had stable disease (SD) of response (HR: 0.084, P=0.004), without liver metastasis (HR:0.271, P=0.008) or less than 2 organs of distance metastatic (HR: 0.263, P=0.005). The average cost per patients in arm A was 153,137 RMB and 165,195 RMB in arm B. While, PF-LYS in arm A was 1.29 times higher than arm B (19,384 vs 15,018 RMB). ConclusionsBoth maintenance therapy strategies are optional for patients who benefit from the initial 6 cycles of therapy. However, there is an advantage on PF-LYS in patients treated with trastuaumab plus single chemotherapy agent. Furthermore, continual single-chemotherapy agent was beneficial in Patients with certain characterisitic. Legal entity responsible for the studyZhongshan Hospital, Fudan University. FundingShanghai Science and Technology Funds 1741195400. DisclosureAll authors have declared no conflicts of interest.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial

ObjectiveAURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. MethodsA decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. ResultsThe ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. ConclusionsDespite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial

ObjectivesTo determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. MethodsA three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. ResultsThe model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97–$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. ConclusionsDose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262.

Is FDA Approved Bevacizumab Cost-Effective in the Setting of Platinum-Resistant Recurrent Ovarian Cancer? [18

INTRODUCTION: The recent FDA approval of inclusion of bevacizumab (BEV) in the treatment of platinum-resistant recurrent ovarian cancer will likely lead to more widespread adoption of this intervention. We assessed the cost effectiveness of this expensive treatment for this specific indication. METHODS: A cost effectiveness decision model was constructed using results from AURELIA, a phase III randomized trial comparing BEV plus cytotoxic chemotherapy versus chemotherapy alone in patients with platinum-resistant recurrent ovarian cancer. The BEV arm of AURELIA had improved progression free survival and quality of life (QOL). Costs, paracentesis rates, and adverse events were incorporated. RESULTS: Inclusion of BEV in the treatment of platinum-resistant recurrent ovarian cancer costs on average $26,790 more than cytotoxic chemotherapy alone when 15 mg/kg dosing is used and $40,813 more when biweekly 10 mg/kg is used. The incremental cost-effectiveness ratio (ICER) per progression-free life year saved (PF-LYS) is $146K with 10 mg/kg dosing and $96K with 15 mg/kg dosing. In sensitivity analysis, the ICER drops below a willingness-to-pay (WTP) threshold of $100K when greater than 68% of patients receive salvage single agent BEV. Incorporating better QOL in the BEV arm based on AURELIA improves the ICER in both dosing regimens, but does not lower the ICER below $100K at the 10 mg/kg dose. CONCLUSION/IMPLICATIONS: Our results suggest that incorporation of BEV using the 15 mg/kg regimen is cost-effective based on the common WTP threshold ICER of $100K. In light of FDA approval for this indication, evidence for cost-effectiveness further supports utilization in women with platinum-resistant recurrent ovarian cancer.

PARP inhibitor maintenance therapy for patients with platinum-sensitive recurrent ovarian cancer: A cost-effectiveness analysis

PurposeTo determine the cost-effectiveness of olaparib, a PARP inhibitor, as maintenance therapy for platinum-sensitive (PS) recurrent ovarian cancer. MethodsTwo separate decision analysis models compared the cost of observation versus olaparib maintenance therapy in patients with PS recurrent ovarian cancer, one for patients with a germline BRCA1/2 mutation and one for patients with wild-type BRCA1/2. Patients received six cycles of paclitaxel and carboplatin. Drug costs were estimated using 2014–2015 wholesale acquisition costs. The cost of olaparib was estimated at $13,440 per month. Rate of germline BRCA1/2 mutation was estimated at 20%. Progression-free survival was determined from published data. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. A sensitivity analysis estimated the cost at which olaparib would be cost-effective. ResultsWe estimated that there were 5549 patients diagnosed with PS recurrent ovarian cancer in the United States annually. The cost of observation in 1110 patients with a BRCA1/2 mutation was $5.5 million (M) versus $169.2M for maintenance therapy with olaparib. The ICER for olaparib maintenance therapy in patients with a BRCA mutation was $258,864 per PF-LYS. If the cost of olaparib was decreased to $2500 per month, the ICER was $49,584. For the 4439 patients with wild-type BRCA, the cost of maintenance therapy was $444.2M; the ICER was $600,552 per PF-LYS. ConclusionsFor patients with a germline BRCA1/2 mutation, maintenance therapy with olaparib is not cost-effective with an ICER of $258,864 per PF-LYS. To achieve an ICER of less than $50,000, the cost of olaparib should be $2500 or less per month. For wild-type BRCA1/2 patients, maintenance therapy with olaparib is not cost-effective.

Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis

ObjectiveThe objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. MethodsA cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. ResultsFor 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. ConclusionsRadiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs.

973PD - Dose-Dense Weekly Paclitaxel and Carboplatin Is More Cost-Effective Than Bevacizumab Plus Triweekly Paclitaxel and Carboplatin for the Primary Treatment of Advanced Ovarian Cancer

ABSTRACT Purpose To determine whether dose-dense weekly paclitaxel and carboplatin (ddPC) is cost effective compared to bevacizumab plus triweekly paclitaxel and carboplatin (PCB) for the primary treatment of advanced ovarian cancer. Methods A cost-effectiveness analysis compared three treatments: 6 cycles of paclitaxel and carboplatin (PC), 6 cycles of PC plus bevacizumab followed by 12 cycles of maintenance bevacizumab (PCB), and 6 cycles of dose-dense weekly paclitaxel and carboplatin (ddPC). Data were taken from reported results of ICON7 (PC and PCB) and JGOG3016 (ddPC). Actual and estimated costs of treatment plus costs of complications were established for each regimen. Progression-free survival and rates of complications were estimated based on the results of clinical trials. Incremental cost-effective ratios (ICER) per progression-free life-year saved (PFLYS) were estimated. Results The ICER for ddPC was $5,000 per PFLYS compared to PC. For PCB compared to PC, the ICER was $285,000 per PFLYS. When compared simultaneously, PCB was more costly and less effective than ddPC. Conclusions In this model, dose-dense weekly paclitaxel and carboplatin is more cost effective than PCB for the treatment of advanced ovarian cancer. Disclosure All authors have declared no conflicts of interest.

An economic analysis of dose dense weekly paclitaxel plus carboplatin versus every-3-week paclitaxel plus carboplatin in the treatment of advanced ovarian cancer

ObjectiveCompared with every-3-week paclitaxel (q3T) plus carboplatin, dose-dense weekly paclitaxel (ddT) plus carboplatin improved the survival of ovarian cancer patients. We performed a cost analysis comparing these two regimens. MethodsUsing a Markov decision model, an acceptable incremental cost-effectiveness ratio (ICER) per progression-free life-year saved (PFLYS) was estimated. Cost of drugs, growth colony-stimulating factors, and transfusions were derived from Medicare reimbursement data. Survival and rates of complications were estimated based on the clinical trial. ResultsUsing a body weight and surface area of an average woman age 63, the estimated cost per cycle of ddT was $107 vs. $80 for q3T. The costs per cycle of combination chemotherapy including treatment administration were $873 for ddT and $535 for q3T. With a median progression-free survival (PFS) of 28months with ddT vs. 17.2months with q3T, the ICER was $5809 per PFLYS for ddT compared with q3T arm. Using a maximum ICER of $100,000 per LYS as cost-effective threshold, the ddT regimen was cost-effective. The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens. A 4-month difference in PFS resulted in a $1200 change of ICER per PFLYS. The ICER was also sensitive to overall survival difference, rate of hematological toxicity, and rate of discontinuation. ConclusionsIn this economic model, dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer.

At What Cost Does a Potential Survival Advantage of Bevacizumab Make Sense for the Primary Treatment of Ovarian Cancer? A Cost-Effectiveness Analysis

To determine whether the addition of bevacizumab to paclitaxel and carboplatin for the primary treatment of advanced ovarian cancer can be cost effective. A cost-effectiveness analysis compared the three arms of the Gynecologic Oncology Group (GOG) 218 study (paclitaxel plus carboplatin [PC], PC plus bevacizumab [PCB], and PCB plus bevacizumab maintenance [PCB+B]). Actual and estimated costs of treatment plus the potential costs of complications were established for each strategy. Progression-free survival (PFS) and bowel perforation rates were taken from recently reported results of GOG 218. Sensitivity analysis was performed for pertinent uncertainties in the model. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were estimated. For the 600 patients entered onto each arm of GOG 218 at the baseline estimates of PFS and bowel perforation, the cost of PC was $2.5 million, compared with $21.4 million for PCB and $78.3 million for PCB+B. These costs led to an ICER of $479,712 per PF-LYS for PCB and $401,088 per PF-LYS for PCB+B. When the cost of bevacizumab was reduced to 25% of baseline, the ICER of PCB+B fell below $100,000 per PF-LYS. ICERs were not substantially reduced when the perforation rate was equal across all arms. The addition of bevacizumab to standard chemotherapy in patients with advanced ovarian cancer is not cost effective. Treatment with maintenance bevacizumab leads to improved PFS but is associated with both direct and indirect costs. The cost effectiveness of bevacizumab in the adjuvant treatment of ovarian cancer is primarily dependent on drug costs.