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Comparative Effectiveness of Up To Three Lines of Chemotherapy Treatment Plans for Metastatic Colorectal Cancer.

ABSTRACT: Modern chemotherapy agents transformed standard care for metastatic colorectal cancer (mCRC) but raised concerns about the financial burden of the disease. We studied comparative effectiveness of treatment plans that involve up to three lines of therapies and impact of treatment sequencing on health and cost outcomes. We employed a Markov model to represent the dynamically changing health status of mCRC patients and used Monte-Carlo simulation to evaluate various treatment plans consistent with existing guidelines. We calibrated our model by a meta-analysis of published data from an extensive list of clinical trials and measured the effectiveness of each plan in terms of cost per quality-adjusted life year. We examined the sensitivity of our model and results with respect to key parameters in two scenarios serving as base case and worst case for patients' overall and progression-free survivals. The derived efficient frontiers included seven and five treatment plans in base case and worst case, respectively. The incremental cost-effectiveness ratio (ICER) ranged between $26,260 and $152,530 when the treatment plans on the efficient frontiers were compared against the least costly efficient plan in the base case, and between $21,256 and $60,040 in the worst case. All efficient plans were expected to lead to fewer than 2.5 adverse effects and on average successive adverse effects were spaced more than 9 weeks apart from each other in the base case. Based on ICER, all efficient treatment plans exhibit at least 87% chance of being efficient. Sensitivity analyses show that the ICERs were most dependent on drug acquisition cost, distributions of progression-free and overall survivals, and health utilities. We conclude that improvements in health outcomes may come at high incremental costs and are highly dependent in the order treatments are administered.

SUBMITTER: Toumazis I

PROVIDER: S-EPMC6124942 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceTo date, limited studies have examined the comparative outcomes of pertuzumab treatment in the real-world setting. End-of-study analyses of the CLEOPATRA trial found median overall survival (OS) of 57.1 months in patients receiving pertuzumab compared with 40.8 months in control patients, a benefit of 16.3 months. However, studies examining the real-world use of pertuzumab have found conflicting results.ObjectiveTo assess the real-world comparative effectiveness and safety of pertuzumab, trastuzumab, and chemotherapy for patients with metastatic breast cancer in Ontario, Canada.Design, setting, and participantsA population-based retrospective comparative effectiveness research study was conducted. Patients receiving first-line treatments for metastatic breast cancer from January 1, 2008, to March 31, 2018, in Ontario were identified. Data analysis was performed from November 13, 2019, to August 1, 2021. Thirteen patients had received treatment before diagnosis or were not Ontario residents and were excluded from the analysis. Of the remaining 1823 patients identified, 912 received pertuzumab and 911 were control patients. Using propensity-score methods, 579 pairs of patients receiving pertuzumab were matched to those in the control group, resulting in a total of 1158 patients in the final cohort.ExposuresPatients in the case group received pertuzumab with trastuzumab and chemotherapy and those in the control group received trastuzumab and chemotherapy.Main outcomes and measuresOverall survival (the primary outcome) and hazard ratios (HRs) were calculated using Kaplan-Meier and Cox proportional hazards regression methods. Secondary outcomes included cumulative incidence of safety end points including resource use and adverse events. Follow-up duration was up to 5 years from the start of therapy, with maximum follow-up to March 31, 2019.ResultsOf the 1158 matched patients (579 pairs) receiving pertuzumab and controls, 1151 (99%) were women (mean [SD] age, 58.2 [12.97] years). The median OS was higher in patients receiving pertuzumab (40.2; 95% CI, 35.6-47.8 months) than in the control patients (25.3; 95% CI, 22.8-27.6 months), a median OS improvement of 14.9 months. Pertuzumab was associated with reduced mortality (HR, 0.66; 95% CI, 0.57-0.79). The cumulative incidence of direct hospitalization at 1 year was lower among patients receiving pertuzumab (11.7%) compared with the control patients (19.0%) (P < .001).Conclusions and relevanceAlthough the median OS in both the pertuzumab and control groups were shorter in this study than those observed in the CLEOPATRA trial, there appears to be a similar significant OS benefit with pertuzumab in the real-world setting.

Project description:The treatment of colorectal cancer is rapidly becoming a significant financial burden to health-care systems within economically developed nations. A current challenge for oncologists and health-care payers is to integrate new, often high-cost, biologic therapies into clinical practice. Inherent to this process is the consideration of cost-effectiveness. The aim of this study was to compare the cost-effectiveness of cetuximab plus irinotecan with an appropriate comparator from a National Health Service (NHS) perspective. This economic evaluation is a trial-based study of cetuximab vs active/best supportive care. Effectiveness estimates for the treatment groups were modelled from key clinical trials. Cunningham et al (2004) compared cetuximab/irinotecan with cetuximab monotherapy; Cunningham et al (1998) compared irinotecan monotherapy in a second-line setting with supportive care. Modelling was necessary owing to an absence of head-to-head clinical trial data of cetuximab/irinotecan vs current standard care. Costs were calculated for the study drugs received, associated administration, palliative chemotherapy for patients in the standard care arm and other nonchemotherapy resources. The discounted life-expectancy of patients treated with cetuximab/irinotecan was 0.91 life-years, and 0.47 discounted life-years for patients receiving active/best supportive care. Patients treated with cetuximab/irinotecan accumulated mean additional costs of 18 901 pounds per patient relative to the comparator arm, with 11 802 pounds attributable to cetuximab. The incremental cost per life-year gained with cetuximab/irinotecan therapy compared with active/best supportive care was 42 975 pounds . The incremental cost per quality adjusted life-year gained was 57 608 pounds . The incremental cost per life-year gained for cetuximab/irinotecan is relatively high compared with other health-care interventions. However, this result should be considered in the context of a number of factors specific to the treated patient population.

Project description:BackgroundThe last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. In addition, there is rising litigation in Brazil in order to access these medicines as they are currently not reimbursed.ObjectiveThe aim was to investigate the comparative effectiveness and safety of three MoAbs (bevacizumab, cetuximab and panitumumab) associated with fluoropyrimidine-based chemotherapy regimens and compared to fluoropyrimidine-based chemotherapy alone in patients with mCRC, through an updated systematic review and meta-analysis of concurrent or non-concurrent observational cohort studies, to guide authorities and the judiciary.MethodA systematic review and meta-analysis was performed based on cohort studies published in databases up to November 2017. Effectiveness measures included OS, PFS, post-progression survival (PPS), Response Evaluation Criteria In Solid Tumors (RECIST), response rate, metastasectomy and safety. The methodological quality of the studies was also evaluated.ResultsA total of 21 observational cohort studies were included. There were statistically significant and clinically relevant benefits in patients treated with bevacizumab versus no bevacizumab mainly around OS, PFS, PPS and the metastasectomy rate, but not for the disease control rates. However, there was an increase in treatment-related toxicities and concerns with the heterogeneity of the studies.ConclusionThe results pointed to an advantage in favor of bevacizumab for OS, PFS, PPS, and metastasectomy. Although this advantage may be considered clinically modest, bevacizumab represents a hope for increased survival and a chance of metastasectomy for patients with mCRC. However, there are serious adverse events associated with its use, especially severe hypertension and gastrointestinal perforation, that need to be considered.

Project description:ImportanceThe KEYNOTE-177 trial demonstrated that patients with metastatic colorectal cancer (MCRC) with high microsatellite instability (MSI-H) and/or mismatch repair deficiency (DMMR) have better outcomes when receiving first-line immune checkpoint inhibitors (ICIs) compared with chemotherapy. Data on performance of ICIs in patients with MCRC in standard practice settings remain limited, and direct MMR vs MSI outcome association comparisons are lacking.ObjectiveTo validate MSI (determined by next-generation sequencing [NGS]) as a biomarker of ICI effectiveness among patients with MCRC in standard practice settings and examine the association of MSI assessed by NGS, DMMR by immunohistochemistry, and tumor mutational burden (cutoff, 10 mutations/megabase) with ICI outcomes.Design, setting, and participantsThis comparative effectiveness research study of outcomes in prospectively defined biomarker subgroups used data from a deidentified clinicogenomic database and included patients who received Foundation Medicine testing (FoundationOne or FoundationOne CDx) during routine clinical care at approximately 280 US academic or community-based cancer clinics between March 2014 and December 2021. The population included 1 cohort of patients with MSI-H MCRC who received first-line ICIs or chemotherapy and a second cohort who received ICIs in any line of therapy (LOT) for biomarker examination.ExposuresICI therapy or chemotherapy assigned at physician discretion without randomization.Main outcomes and measuresThe main outcomes were time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS). Hazard ratios were adjusted for known prognostic imbalances. Comparisons of explanatory power used the likelihood ratio test.ResultsA total of 138 patients (median age, 67.0 years [IQR, 56.2-74.0 years]; 73 [52.9%] female) with MSI-H MCRC received first-line ICIs or chemotherapy. A total of 182 patients (median age, 64.5 years [IQR, 55.2-72.0]; 98 [53.8%] female) received ICIs in any LOT. Patients receiving first-line ICIs vs chemotherapy had longer TTNT (median, not reached [NR] vs 7.23 months [IQR, 6.21-9.72 months]; adjusted hazard ratio [AHR], 0.17; 95% CI, 0.08-0.35; P < .001), PFS (median, 24.87 months [IQR, 19.10 months to NR] vs 5.65 months [IQR, 4.70-8.34 months]; AHR, 0.31; 95% CI, 0.18-0.52; P < .001), and OS (median, NR vs 24.1 months [IQR, 13.90 months to NR]; HR, 0.45; 95% CI, 0.23-0.88; P = .02). MSI added to DMMR better anticipated TTNT and PFS in patients receiving ICIs than DMMR alone. The same was not observed when DMMR evaluation was added to MSI.Conclusions and relevanceIn this comparative effectiveness research study, MSI assessed by NGS robustly identified patients with favorable outcomes on first-line ICIs vs chemotherapy and appeared to better anticipate ICI outcomes compared with DMMR.

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Comparative Effectiveness of Up To Three Lines of Chemotherapy Treatment Plans for Metastatic Colorectal Cancer.

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