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1500PPatients with metastatic non-small cell lung cancer without molecular alterations or PD-L1 expression in Germany: Treatment and first outcome from the prospective German Registry Platform CRISP (AIO-TRK-0315)
Abstract
Background
Guidelines for metastatic non-small cell lung cancer recommend stratified treatment by biomarker test results. We used CRISP to evaluate treatment and outcome of patients (pts) in whom neither targetable molecular alterations nor any PD-L1 expression were detected.
Methods
Currently 163 sites in Germany have recruited >3700 pts at start of 1st-line who will be followed until death or end of project. Data from 2204 pts recruited by 133 sites from 12/2015 to 06/2018 was analyzed. These pts started treatment prior approval of immune checkpoint inhibitors (ICI) for this group of pts. Progression-free survival (PFS) was determined in pts ≥1 year under observation (recruited until 06/2017 (n = 906), outcome sample (ous)).
Results
6% of pts with non-squamous (nsq) and 35% with squamous (sq) tumors received no type of biomarker testing prior to start of 1st-line, and in 49% and 36% no targetable alterations or any PD-L1 expression were detected. Thus, 55% and 71% of pts (nsq/sq) were eligible for chemotherapy (ctx) but no type of targeted therapy at start of 1st-line. Median age at start of 1st-line was 66 and 68 years (nsq/sq). 29%/23% had ECOG=0 and 82%/90% ≤1 comorbidity. 10%/6% were never-smokers. In 1st-line, pts received carboplatin- (55%) or cisplatin-based ctx (24%), 13% targeted therapy (e.g. ICI in trial, switch to TKI but test result not yet documented). At database cut, 33% of all pts had started 2nd-line, 24% had died prior to a 2nd-line and remaining pts were still in 1st-line. In the ous, median PFS was 5.0 months (66% events, 95%-CI 4.5-5.5 months, n = 457) for nsq tumors and 4.5 months (66% events, 95%-CI 3.4-5.3 months, n = 154) for sq tumors. In total 55% of pts with nsq and 53% of pts with sq tumors had died.
Conclusions
CRISP presents current real life data from Germany. Despite break-throughs with targeted therapies and high test rates in routine care, the majority of pts do not qualify for targeted therapy because no targetable alterations are found. First outcome results indicate that prognosis is poor in these pts. Outcome will hopefully improve in the cohort now treated with ctx-ICI combination.
Clinical trial identification
NCT02622581.
Legal entity responsible for the study
AIO-Studien-gGmbH.
Funding
AstraZeneca GmbH, Boehringer Ingelheim Pharma GmbH & Co. KG, Bristol-Myers Squibb GmbH & Co. KGaA, Celgene GmbH, MSD Sharp & Dohme GmbH, Lilly Deutschland GmbH, Novartis Pharma GmbH, Pfizer Pharma GmbH, Roche Pharma AG, and Takeda Pharma Vertriebs GmbH & Co. KG.
Disclosure
F. Griesinger: Honoraria (self), Advisory / Consultancy: Ariad; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myer-Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Celgene; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Merck-Sharp-Dome; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche. N.W. Marschner: Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (institution), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Research grant / Funding (institution): MSD Sharp & Dohme ; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Leadership role, Shareholder / Stockholder / Stock options, Officer / Board of Directors: iOMEDICO. M. Jänicke: Leadership role, Full / Part-time employment: iOMEDICO. A. Fleitz: Full / Part-time employment: iOMEDICO. L. Spring: Full / Part-time employment: iOMEDICO. J. Sahlmann: Leadership role, Full / Part-time employment: iOMEDICO. A. Karatas: Research grant / Funding (institution): AstraZeneca ; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Takeda. A. Hipper: Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): MSD Sharp & Dohme; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): AstraZeneca. M. Sebastian: Advisory / Consultancy: Bristol-Myers Squibb ; Advisory / Consultancy: MSD Sharp & Dohme ; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim Pharma; Advisory / Consultancy: Celgene; Advisory / Consultancy: Lilly; Advisory / Consultancy: Pfizer. M. Thomas: Advisory / Consultancy, Travel / Accommodation / Expenses: MSD Sharp & Dohme ; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb ; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca ; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis. All other authors have declared no conflicts of interest.
... Approximately 18-28% of patients with NSCLC have PD-L1 expression of 50% or greater [6,10,[18][19][20]. International guidelines, as well as those specific to Europe and Germany-the latter serving in this study as a model to analyze cost-effectiveness of PD-L1 testing-recommend testing for PD-L1 expression in all patients with advanced NSCLC [21][22][23][24][25]. ...
... For costing purposes, we used the median of five cycles with optional maintenance therapy until disease progression, death, or 1 year was reached. Chemotherapy treatments in the model (70% carboplatin containing and 30% cisplatin containing) were based on the actual combinations selected by investigators in KEY-NOTE-024, which was consistent with German treatment patterns reported in the CRISP registry [19][20][21]. The CRISP registry does not further specify therapy types beyond containing either carboplatin or cisplatin. ...
... German treatment guidelines recommend platinum-containing chemotherapy as a secondline treatment for pembrolizumab patients who have disease progression [34]. Based on treatment patterns reported by the KEYNOTE-024 trial, CRISP registry, and German treatment guidelines, the model assumed second-line monotherapy with either carboplatin (70%) or cisplatin (30%) [8,[19][20][21]34]. ...
Introduction:
Accurate PD-L1 testing for non-small cell lung cancer (NSCLC) maximizes the benefits of immune checkpoint inhibitor (ICI) drugs like pembrolizumab. False negative test results deny ICI treatments to eligible patients, worsening clinical and economic outcomes, while false positives increase costs by using ICI treatments without their benefits. This study evaluates the cost-effectiveness of PD-L1 testing with an in vitro diagnostic (IVD) compared to a laboratory-developed test (LDT) for allocating patients with NSCLC to treatment with either pembrolizumab or chemotherapy using the German healthcare system as a model.
Methods:
We developed a decision analytical model to evaluate the cost-effectiveness of PD-L1 testing with a regulatory body approved IVD compared to an LDT from the national German healthcare payer (statutory health insurance system) perspective. Accuracy of PD-L1 testing was based on data from two independent proficiency testing programs. The 1-year model was based on outcomes data from the KEYNOTE-024 clinical trial and treatment patterns reflecting current German practices.
Results:
IVDs produced accurate PD-L1 testing results in 93% (752/811) of tested cases compared to 73% (492/672) with LDTs. Most misclassifications concerned false negatives, occurring in 21% of LDTs vs 7% of IVDs. Total costs of the IVD group (48,878 €) were 196 € higher than the LDT group (48,682 €). These costs incorporate testing, first- and second-line therapy, managing treatment-related grade 3+ adverse events (AEs), and end-of-life costs for those who died within the year. Total effectiveness (percentage of patients successfully diagnosed and prescribed the correct therapy per German treatment guidelines) was 19 percentage points higher for the IVD group (88%) compared to the LDT group (69%). These differences in costs and effects lead to an incremental cost-effectiveness ratio (ICER) of 1057 €.
Conclusion:
Compared to LDT technology, on-label IVD use for PD-L1 testing is only slightly more costly and substantially more effective for aligning patients with PD-L1-positive NSCLC with ICI therapy according to German practice guidelines. Given these findings, changes to testing and reimbursement policies may be considered to maximize patient outcomes in NSCLC.
The benefits of ICIs for patients (pts) with NSCLC have been shown in several clinical trials
- Bristol-Myers
- Squibb
- N J Princeton
- Background
Global Medical Affairs, Bristol-Myers Squibb, Madrid, Spain, 4 Worldwide Health
Economics & Outcomes Research, Bristol-Myers Squibb, Princeton, NJ, USA
Background: The benefits of ICIs for patients (pts) with NSCLC have been shown in
several clinical trials, but real-world data are limited. We describe the early impact of 2L