The Impact of Response at A Landmark on Overall Survival: Implications for the Economic Evaluation of the Value of Immuno-Oncology (I-O) Treatment in Non-Small Cell Lung Cancer (NSCLC)

Santi, Irene; Johal, Sukhvinder; Yuan, Yong; Penrod, JR

doi:10.1016/j.jval.2018.04.1436

Cited by 3 publications

(9 citation statements)

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“…In most patients with a complete or partial response, responses were observed within the first 6 months of treatment and were ongoing at 6 months; few responses occurred after this timepoint. A previous sensitivity analysis 15 of data from CheckMate 057 showed that landmark survival assessed at 4 and 8 months yielded results that were qualitatively similar to those at 6 months, providing the rationale for using the 6-month timepoint in the current analyses.…”

Section: Methodsmentioning

confidence: 85%

“…All authors had full access to all of the data in the analyses, and the corresponding author had final responsibility for the decision to submit for publication. , and the estimated 4-year overall survival was 14% (95% CI 11-17; figure 1) The estimated 4-year overall survival was higher in patients with at least 1% PD-L1 expression (19% [95% CI [15][16][17][18][19][20][21][22][23][24]) than in those with less than 1% PD-L1 expression (11% [7][8][9][10][11][12][13][14][15][16]; appendix p 16), but was similar between patients with squamous and non-squamous tumour histology (appendix p 17). Baseline characteristics of nivolumab-treated patients who survived for at least 4 years are shown in the appendix (p 7).…”

Section: Role Of the Funding Sourcementioning

confidence: 99%

“…The estimated median overall survival post-progression for all patients who progressed was 6•6 months (95% CI 5•7-7•7) and 3-year overall survival from time to progression was 8% (6-11; appendix p 24). However, 3-year overall survival post-progression was higher for patients who progressed after a best overall response of complete or partial response (29% [95% CI 18-41]) or stable disease (12% [7][8][9][10][11][12][13][14][15][16][17][18]) than for patients with a best overall response of progressive disease (3% [1][2][3][4][5]). Compared with progressive disease as best overall response, a best overall response of complete or partial response had an HR for postprogression death of 0 Overall survival outcomes with nivolumab in the pooled CheckMate 017 and 057 population (figure 1) were similar to those in the pooled analysis of the four studies (figure 1), and median overall survival was substantially longer with nivolumab than with docetaxel.…”

Section: Acrossmentioning

confidence: 99%

“…The 4year overall survival was higher with nivolumab (14% [95% CI 11-18]) than with docetaxel (5% [3][4][5][6][7]; figure 1). The 4-year overall survival was higher with nivolumab (9% [95% CI 5-14]) than that with docetaxel (4% [2][3][4][5][6][7][8]) in patients with less than 1% PD-L1 expression and higher with nivolumab (20% [14][15][16][17][18][19][20][21][22][23][24][25][26]) than with docetaxel (5% [2][3][4][5][6][7][8]) in patients with at least 1% PD-L1 expression (appendix p 26).…”

Section: Acrossmentioning

confidence: 99%

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Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis

Antonia

Borghaei

Ramalingam

et al. 2019

The Lancet Oncology

285

243

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Background-Phase 3 clinical data has shown higher proportions of patients with objective response, longer response duration, and longer overall survival with nivolumab versus docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We aimed to evaluate the long-term benefit of nivolumab and the effect of response and disease control on subsequent survival. Methods-We pooled data from four clinical studies of nivolumab in patients with previously treated NSCLC (CheckMate 017, 057, 063, and 003) to evaluate survival outcomes. Trials of nivolumab in the second-line or later setting with at least 4 years follow-up were included. Comparisons of nivolumab versus docetaxel included all randomised patients from the phase 3 CheckMate 017 and 057 studies. We did landmark analyses by response status at 6 months to determine post-landmark survival outcomes. We excluded patients who did not have a radiographic tumour assessment at 6 months. Safety analyses included all patients who received at least one dose of nivolumab. Findings-Across all four studies, 4-year overall survival with nivolumab was 14% (95% CI 11-17) for all patients (n=664), 19% (15-24) for those with at least 1% PD-L1 expression, and 11% (7-16) for those with less than 1% PD-L1 expression. In CheckMate 017 and 057, 4-year overall survival was 14% (95% CI 11-18) in patients treated with nivolumab, compared with 5% (3-7) in patients treated with docetaxel. Survival subsequent to response at 6 months on nivolumab or docetaxel was longer than after progressive disease at 6 months, with hazard ratios for overall survival of 0•18 (95% 0•12-0•27) for nivolumab and 0•43 (0•29-0•65) for docetaxel; for stable disease versus progressive disease, hazard ratios were 0•52 (0•37-0•71) for nivolumab and 0•80 (0•61-1•04) for docetaxel. Long-term data did not show any new safety signals. Interpretation-Patients with advanced NSCLC treated with nivolumab achieved a greater duration of response compared with patients treated with docetaxel, which was associated with a long-term survival advantage. Funding-Bristol-Myers Squibb.

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Section: Methodsmentioning

confidence: 85%

Section: Role Of the Funding Sourcementioning

confidence: 99%

Section: Acrossmentioning

confidence: 99%

Section: Acrossmentioning

confidence: 99%

See 2 more Smart Citations

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis

Antonia

Borghaei

Ramalingam

et al. 2019

The Lancet Oncology

285

243

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“…The result is a potential loss of statistical power to demonstrate the difference between the treatment arms. 11 Alternative metrics exist that suit the IO mechanism of action, including landmark survival analysis 48 and restricted mean survival time. 9 Both capture the survival benefit in the tail of the curve, and landmark survival analysis can also better capture the changing hazard function over time and provide data to support the plateauing effect.…”

Section: Biomarkersmentioning

confidence: 99%

Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective

Quinn¹,

Garrison

Pownell³

et al. 2020

J Immunother Cancer

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Immuno-oncologics (IOs) differ from chemotherapies as they prime the patient’s immune system to attack the tumor, rather than directly destroying cancer cells. The IO mechanism of action leads to durable responses and prolonged survival in some patients. However, providing robust evidence of the long-term benefits of IOs at health technology assessment (HTA) submission presents several challenges for manufacturers. The aim of this article was to identify, analyze, categorize, and further explore the key challenges that regulators, HTA agencies, and payers commonly encounter when assessing the long-term benefits of IO therapies. Insights were obtained from an international, multi-stakeholder steering committee (SC) and expert panels comprising of payers, economists, and clinicians. The selected individuals were tasked with developing a summary of challenges specific to IOs in demonstrating their long-term benefits at HTA submission. The SC and expert panels agreed that standard methods used to assess the long-term benefit of anticancer drugs may have limitations for IO therapies. Three key areas of challenges were identified: (1) lack of a disease model that fully captures the mechanism of action and subsequent patient responses; (2) estimation of longer-term outcomes, including a lack of agreement on ideal methods of survival analyses and extrapolation of survival curves; and (3) data limitations at the time of HTA submission, for which surrogate survival end points and real-world evidence could prove useful. A summary of the key challenges facing manufacturers when submitting evidence at HTA submission was developed, along with further recommendations for manufacturers in what evidence to produce. Despite almost a decade of use, there remain significant challenges around how best to demonstrate the long-term benefit of checkpoint inhibitor-based IOs to HTA agencies, clinicians, and payers. Manufacturers can potentially meet or mitigate these challenges with a focus on strengthening survival analysis methodology. Approaches to doing this include identifying reliable biomarkers, intermediate and surrogate end points, and the use of real-world data to inform and validate long-term survival projections. Wider education across all stakeholders—manufacturers, payers, and clinicians—in considering the long-term survival benefit with IOs is also important.

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Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer

Smare

Dave

Juarez-Garcia

et al. 2021

Journal of Medical Economics

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Aims: Present cost-effectiveness analysis of nivolumab monotherapy vs commonly prescribed third-line (3L+) treatment in small cell lung cancer (SCLC). Materials and methods:A three health states partitioned survival model (progression-free, progressed disease, and death; US payer perspective) was developed. Systematic literature review identified no randomized controlled or single-arm trials with separate outcomes for 3L+ SCLC patients. Topotecan was chosen as comparator because it is frequently prescribed in realworld practice for 3L SCLC. Clinical inputs for topotecan were derived from the Flatiron database with inclusion/exclusion criteria matched to patients treated with 3L+ nivolumab in CheckMate 032. Intravenous (IV) and oral topotecan clinical efficacy were assumed equivalent.Base-case analysis used a 20-year lifetime horizon. An annual discount rate of 3.0% for costs and outcomes was applied. Uncertainty was assessed using sensitivity analyses adjusted for key parameters.Results: Incremental cost per quality-adjusted life-year (QALY) gained with nivolumab was US$153,312 vs IV topotecan and US$123,003 vs oral topotecan, respectively. When results were disaggregated, nivolumab-related costs were mainly driven by drug acquisition costs, and topotecan-related costs were primarily due to adverse event treatment. Mean overall survival (OS) was 21.69 months with nivolumab and 5.80 months with IV or oral topotecan. More favorable outcomes were found by the landmark response analyses. Deterministic sensitivity analyses showed that changes to the discount rate for costs and outcomes and body weight had the greatest impacts on results. A c c e p t e d M a n u s c r i p t Limitations: Included use of real-world data for OS outcomes associated with 3L topotecan, use of second-line topotecan data for progression-free survival, and no indirect costs. Conclusions:Based on the literature on willingness-to-pay for a QALY in metastatic cancer, nivolumab monotherapy might represent a cost-effective option for 3L+ treatment of SCLC compared with IV and oral topotecan. Sensitivity analysis using response-based methods yielded further favorable cost-effectiveness estimates.

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The Impact of Response at A Landmark on Overall Survival: Implications for the Economic Evaluation of the Value of Immuno-Oncology (I-O) Treatment in Non-Small Cell Lung Cancer (NSCLC)

Cited by 3 publications

References 0 publications

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis

Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis

Current challenges for assessing the long-term clinical benefit of cancer immunotherapy: a multi-stakeholder perspective

Cost-effectiveness of nivolumab monotherapy in the third-line treatment of small cell lung cancer

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