Dataset Information

Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial.

ABSTRACT:

Objective

The phase III POLO trial demonstrated that olaparib as maintenance therapy for metastatic pancreatic cancer patients with a germline BRCA mutation had greater efficacy than placebo, but maintenance olaparib places an economic burden on patients. This study evaluated the cost-effectiveness of olaparib as maintenance therapy based on the POLO trial (NCT02184195).

Methods

A three-state Markov model (progression-free survival [PFS], progressive disease [PD] and death) based on data from the POLO trial was used to estimate the incremental cost-effectiveness ratio (ICER) of maintenance olaparib versus placebo for metastatic pancreatic cancer patients with a germline BRCA mutation. The cost was evaluated from the Chinese society's perspective, and health outcomes were assessed in terms of quality-adjusted life years (QALYs). The primary outcome was the ICER gained in terms of 2019 US$ per QALY. Model robustness was explored with one-way and probabilistic sensitivity analyses.

Results

Compared with placebo, maintenance olaparib increased costs by $23,544.35 while gaining 0.69 QALYs, resulting in an ICER of $34,122.25 per QALY. The ICER was far higher than the commonly accepted willingness-to-pay threshold ($28,255.55 per QALY).

Conclusion

Compared with placebo, maintenance olaparib for metastatic pancreatic cancer patients with a germline BRCA mutation is not cost-effective in China.

SUBMITTER: Zhan M

PROVIDER: S-EPMC7751318 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial.

Zhan Mei M Zheng Hanrui H Yang Yu Y He Zhiyao Z Xu Ting T Li Qiu Q

Cancer management and research 20201216

<h4>Objective</h4>The phase III POLO trial demonstrated that olaparib as maintenance therapy for metastatic pancreatic cancer patients with a germline BRCA mutation had greater efficacy than placebo, but maintenance olaparib places an economic burden on patients. This study evaluated the cost-effectiveness of olaparib as maintenance therapy based on the POLO trial (NCT02184195).<h4>Methods</h4>A three-state Markov model (progression-free survival [PFS], progressive disease [PD] and death) based ...[more]

PMID: 33364840

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Project description:BackgroundPatients with a germline BRCA1 or BRCA2 mutation make up a small subgroup of those with metastatic pancreatic cancer. The poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib has had antitumor activity in this population.MethodsWe conducted a randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy of olaparib as maintenance therapy in patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer and disease that had not progressed during first-line platinum-based chemotherapy. Patients were randomly assigned, in a 3:2 ratio, to receive maintenance olaparib tablets (300 mg twice daily) or placebo. The primary end point was progression-free survival, which was assessed by blinded independent central review.ResultsOf the 3315 patients who underwent screening, 154 underwent randomization and were assigned to a trial intervention (92 to receive olaparib and 62 to receive placebo). The median progression-free survival was significantly longer in the olaparib group than in the placebo group (7.4 months vs. 3.8 months; hazard ratio for disease progression or death, 0.53; 95% confidence interval [CI], 0.35 to 0.82; P = 0.004). An interim analysis of overall survival, at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months vs. 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P = 0.68). There was no significant between-group difference in health-related quality of life, as indicated by the overall change from baseline in the global quality-of-life score (on a 100-point scale, with higher scores indicating better quality of life) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (between-group difference, -2.47 points; 95% CI, -7.27 to 2.33). The incidence of grade 3 or higher adverse events was 40% in the olaparib group and 23% in the placebo group (between-group difference, 16 percentage points; 95% CI, -0.02 to 31); 5% and 2% of the patients, respectively, discontinued the trial intervention because of an adverse event.ConclusionsAmong patients with a germline BRCA mutation and metastatic pancreatic cancer, progression-free survival was longer with maintenance olaparib than with placebo. (Funded by AstraZeneca and others; POLO ClinicalTrials.gov number, NCT02184195.).

Project description:BACKGROUND:Patients with metastatic pancreatic cancer often have a detriment in health-related quality of life (HRQoL). In the randomized, double-blind, phase III POLO trial progression-free survival was significantly longer with maintenance olaparib, a poly(ADP-ribose) polymerase inhibitor, than placebo in patients with a germline BRCA1 and/or BRCA2 mutation (gBRCAm) and metastatic pancreatic cancer whose disease had not progressed during first-line platinum-based chemotherapy. The prespecified HRQoL evaluation is reported here. PATIENTS AND METHODS:Patients were randomized to receive maintenance olaparib (300?mg b.i.d.; tablets) or placebo. HRQoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item module at baseline, every 4?weeks until disease progression, at discontinuation, and 30?days after last dose. Scores ranged from 0 to 100; a ?10-point change or difference between arms was considered clinically meaningful. Adjusted mean change from baseline was analysed using a mixed model for repeated measures. Time to sustained clinically meaningful deterioration (TSCMD) was analysed using a log-rank test. RESULTS:Of 154 randomized patients, 89 of 92 olaparib-arm and 58 of 62 placebo-arm patients were included in HRQoL analyses. The adjusted mean change in Global Health Status (GHS) score from baseline was <10 points in both arms and there was no significant between-group difference [-2.47; 95% confidence interval (CI) -7.27, 2.33; P?=?0.31]. Analysis of physical functioning scores showed a significant between-group difference (-4.45 points; 95% CI -8.75, -0.16; P?=?0.04). There was no difference in TSCMD for olaparib versus placebo for GHS [P?=?0.25; hazard ratio (HR) 0.72; 95% CI 0.41, 1.27] or physical functioning (P?=?0.32; HR 1.38; 95% CI 0.73, 2.63). CONCLUSIONS:HRQoL was preserved with maintenance olaparib treatment with no clinically meaningful difference compared with placebo. These results support the observed efficacy benefit of maintenance olaparib in patients with a gBRCAm and metastatic pancreatic cancer. CLINCALTRIALS.GOV NUMBER:NCT02184195.

Project description:RATIONALE:Pancreatic cancer (PC) is considered as one of the deadliest cancers all over the world. Germline and somatic BRCA1/2 mutations have been widely studied in breast and ovarian carcinomas as they have been found to enhance the risk for disease progression. Olaparib, an oral poly(adenosine diphosphate-ribose)polymerase (PARP) inhibitor, has been approved for the treatment strategy of ovarian cancer with any BRCA1/2 mutations. There is a lack of studies which focus on the treatment of other cancer with BRCA-Mutation. PATIENT CONCERNS:This report describes a patient whose presenting complaints were "Physical examination showed that the pancreas was occupied for one month." He initially was diagnosed with stage IV PC based on conventional imaging and pathologic assessment. He had a known germline BRCA 2 mutation, which exhibited a good response to PARP inhibitor therapy. DIAGNOSIS:Through the biopsy histopathological examination, imaging examination, and genetic testing, the patient was diagnosed as metastatic PC with BRCA2 mutation. INTERVENTIONS:He received gemcitabine and albumin-bound paclitaxel chemotherapy from March 15, 2017 to June 30, 2017, and Nivolumab immunotherapy as the maintenance therapy. After serum CA-199 level increased, Olaparib was orally administered from August 17, 2017 to March. After tumor relapsed, he received multiple lines of chemotherapy, including Trametinib Oxaliplatin, S-1, bevacizumab, and irinotecan liposome injection till July 17, 2018. OUTCOMES:We observed the patient had a good progression-free survival (7.4 months); the lesion of the pancreas was classified as partial disease through Olaparib treatment, which indicated significant shrinkage. But it is difficult to conclude whether such therapy could help prolong the overall survival for such patients. LESSONS:The targeted therapy Olaparib showed early signs of potential in treating PC in patients with mutations of the BRCA genes. With emerging therapeutic modalities and next-generation sequencing development, it is increasingly relevant to consider mutation screenings of patients with PC.

Project description:Purpose: The effectiveness of poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitor olaparib for metastatic castration-resistant prostate cancer (MCRPC) with multiple loss-of-function alterations in genes that are involved in DNA repair has been demonstrated. We aimed to evaluate the cost-effectiveness of genomic test-directed olaparib on MCRPC from the US payer perspective. Methods: A partitioned survival model was adopted to project the disease course of MCRPC had at least one gene alteration in BRCA1, BRCA2 and ATM (Scenario A) and has alterations in any of all 15 prespecified genes (Scenario B) after next-generation sequencing test. The efficacy and toxicity data were gathered from the PROfound trial. Clinical probabilities related to survival were estimated from the reported survival probabilities in each PROfound group. Cost and health preference data were derived from the literature. The incremental cost-effectiveness ratio (ICER) was measured. Subgroup analysis and sensitivity analysis were performed for exploring the model uncertainties. Results: Olaparib yielded an additional 0.063 and 0.068 of quality-adjusted life year (QALY) with the augmented cost of $7,382 and saved the cost of $ 1,980 compared to standard care in scenario A and B, respectively, which yielded an ICER of $116,903/QALY and a cost-saving option. The lower weekly cost related to olaparib treatment led to the dominant findings in scenario B. The varied results between scenario A and B could be partly explained by different the number need to screen for identifying eligible patients who could be administered with olaparib, which sharply augmented the costs of the olaparib arm in scenario A. Subgroup analysis and sensitivity analysis revealed the results were generally robust in both of two scenarios. Conclusion: The genomic test-directed olaparib is a preferred option compared with standard care strategy for men with MCRPC who had any of all 15 prespecified genes.

Project description:ImportanceUnregulated drug prices increase cancer therapy costs. After induction chemotherapy, patients with metastatic colon cancer can receive maintenance capecitabine and bevacizumab therapy based on improved progression-free survival, but whether this treatment's cost justifies its benefits has not been evaluated in the United States.ObjectiveThis study sought to determine the influence of capecitabine and bevacizumab drug prices on cost-effectiveness from a Medicare payer's perspective.Design, setting, and participantsThe incremental cost-effectiveness of capecitabine and bevacizumab maintenance therapy was determined with a Markov model using a quality-of-life penalty based on outcomes data from the CAIRO phase 3 randomized clinical trial (RCT), which included 558 adults in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. The outcomes were modeled using Markov chains to account for patients who had treatment complications or cancer progression. Transition probabilities between patient states were determined, and each state's costs were determined using US Medicare data on payments for capecitabine and bevacizumab treatment. Deterministic and probabilistic sensitivity analyses identified factors affecting cost-effectiveness.Main outcomes and measuresLife-years gained were adjusted using CAIRO3 RCT quality-of-life data to determine quality-adjusted life-years (QALYs). The primary end point was the incremental cost-effectiveness ratio, representing incremental costs per QALY gained using a capecitabine and bevacizumab maintenance regimen compared with observation alone.ResultsMarkov model estimated survival and complication outcomes closely matched those reported in the CAIRO3 RCT, which included 558 adults (n = 197 women, n = 361 men; median age, 64 and 63 years for patients in the observation and maintenance therapy groups, respectively) in the Netherlands with unresectable metastatic colorectal cancer who had stable disease or better following induction chemotherapy. Incremental costs for a 3-week maintenance chemotherapy cycle were $6601 per patient. After 29 model iterations corresponding to 60 months of follow-up, mean per-patient costs were $105 239 for maintenance therapy and $21.10 for observation. Mean QALYs accrued were 1.34 for maintenance therapy and 1.20 for observation. The incremental cost-effectiveness ratio favored maintenance treatment, at an incremental cost of $725 601 per QALY. The unadjusted ratio was $438 394 per life-year. Sensitivity analyses revealed that cost-effectiveness varied with changes in drug costs. To achieve an incremental cost-effectiveness ratio of less than $59 039 (median US household income) per unadjusted life-year would require capecitabine and bevacizumab drug costs to be reduced from $6173 (current cost) to $452 per 3-week chemotherapy cycle.Conclusions and relevanceAntineoplastic therapy is expensive for payers and society. The price of capecitabine and bevacizumab maintenance therapy would need to be reduced by 93% to make it cost-effective, a finding useful for policy decision making and payment negotiations.

Dataset Information

Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial.

Objective

Methods

Results

Conclusion

Publications

Cost-Effectiveness Analysis of Maintenance Olaparib in Patients with Metastatic Pancreatic Cancer and a Germline BRCA1/2 Mutation Based on the POLO Trial.

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