The Impact of The Immune Check Point on Cost in Lung Cancer: Duration of use
Main Article Content
Abstract
Background: Monotherapy and combinations of Pembrolizumab (Pembro), Atezolizumab (Atezo) and Cemiplimab (Cemi), prolonged overall survival (OS) in advanced/metastatic non-small cell lung cancer (a/m NSCLC). Pembro demonstrated 5-year OS gain. The duration of therapy of the immune check point inhibitors (ICI) has not been defined. One-year adjuvant Durvalumab (Durv) and Atezo significantly extended OS. Neoadjuvant few cycles resulted in positive outcomes. ICI costs are relatively expensive and multiply with further use with no containment on sight. The 2019 CAR-T cost was limited to $450,000. There are unmet needs for coherent drug cost policies. We aimed 1- Explore the factors which impact ICI costs in lung cancer 2- Navigate cost-saving strategy based on generics, therapy duration 3- Explore the possibility whether adjuvant and neoadjuvant treatment impact costs
Methods: Annual drug prices were quoted and calculated. Utilization thresholds were set for ICI monotherapy at $450,000 and combinations at $550,000.
Results: Estimated annual Pemetrexed (Peme) costs were $113,793, generic chemicals < $1,000 and Bevacizumab (Bev) $150,126. The mean of 6 ICI was $148,000. Pembro 2-year costs were $334,652, below the the proposed $450,000 thresolds. The 3-year costs of $501,978 and the 5-year $836,630 were above $450,000. Atezo + Bev+ Peme combination had the highest 2-year $722,977 costs, above $550,000. There was no significant difference in cost between Atezo + Peme $422,725, Pembro + Peme $448,445 and Cemi + Peme $425,385. These combinations were below the $550,000 threshold. Costs decreased using generics by 25%. Extending ICI use by 6-12 months increased combination costs by 25-50%. Adjuvant 1-year Durv costs were $148,013 and Atezo $154,446, half the 2-year. Using response rates, cost of 2-4 cycles of neoadjuvant Nivolumab (Nivo) were only $25,000 - $50,000.
Conclusion: Generics, limited ICI duration, utilization thresholds and neoadjuvant therapy significantly reduced drug costs. Neoadjuvant therapy had the highest impact on cost reduction.
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References
2-Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med. 2015; 372:2018–28.
3-Garon EB, et al. Pembrolizumab monotherapy 5-year data from KEYNOTE-001 in patients with advanced non–small cell lung cancer (NSCLC), ASCO annual meeting, Chicago, May 2019 (Abstract LBA9015)
4- Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small lung cancer. N Engl J med. 2016: 375:823-833.
5- Reck M, Rodriguez-Abreu D. Updated analysis of KEYNOTE-024: Pembrolizumab vs. platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. JCO 37, nb 7, 537-546, 2019.
6-Herbst RS, Gluseppe G, de Marinis F, et al, Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. NEJM2020, 383,1328-1339.
7- Sezer A, Kilickap S, Gümüş M, et al. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021;397(10274):592-604.
8-Gandhi L, Rodriguez-Abreu D, Gadgeel S, et al. Pembrolizumab plus chemotherapy in Metastatic Non-Small-Cell Lung Cancer (KEYNOTE-189), N Engl J Med. 378 (22): 20782092, 2018
9-Reck M, Socinski MA, Cappuzzo F, et al. LBA1_PR primary PFS and safety analyses of a randomized phase III study of carboplatin + paclitaxel +/? bevacizumab, with or without atezolizumab in 1L non-squamous metastatic NSCLC (IMPOWER150). (NTC0236614) Ann Oncol. 2017; 28 (Suppl 11) 1 December 2017, mdx760.002
10-Kowanetz M, Socinski MA, Zou W, et al. IMpower150: Efficacy of atezolizumab (atezo) plus bevacizumab (bev) and chemotherapy (chemo) in 1L metastatic nonsquamous NSCLC (mNSCLC) across key subgroups. ASCO, Program and abstracts 2018 annual meeting: April 14-18, 2018; Chicago, Illinois. Abstract CT076.
11-Socinski, MA. IMPOWER 130/132/150 pooled irAEs, ASCO 2021 annual meeting: Chicago, Illinois.
12- Regeneron Pharmaceuticals Inc. Phase 3 trial OF Libtayo® (cemiplimab-rwlc) combined with chemptherapy in patients with first-line Advanced non-small cell lung cancer.https://www.prnewswire.com/news-releases/phase-3-trial-of-libtayo-cemiplimab-rwlc-combined-with-chemotherapy-stopped-early-due-to-significant-improvement-in-overall-survival-in-patients-with-first-line-advanced-non-small-cell-lung-cancer-301348999.html. Accessed September 9, 2021.
13-Hellmann MD, Ciuleanu TE, Pluzanski A, et al. Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med. 2018;378(22):2093-2104
14-Reck M, Ciuleanu TE, Cobo Dols M, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy 17 (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA. J Clin Oncol. 2020;38 (suppl; abs 9501). doi:10. 1200/JCO.2020.38.15, suppl.9501.
15-Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemo-radiotherapy in stage III NSCLC. N Engl J Med. 2018, 379:2342-2350 DOI:10.1056//NEJMoa1809697
16-Wakelee HA, Altorki NK, Zhoe C et al. Impower010: Primary results of a III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected IB-IIIA non-small cell lung cancer (NSCLC)(ASCO), Abstract 8500: J Clin Onc.2021:39 (15) (suppl).
17-Lin JK and colleagues. CAR T-CELL therapies may be cost effective for DLBCL. HemOnctoday, Sep 25, 2019.15
16-Schnipper LE, Davidson NE, Wollins DS, et al. American Society of Clinical Oncology statement: A framework to assess the value of cancer treatment options. J Clin Oncol. June 22, 2015.
17-Schnipper LE, Davidson NE, Wollins DS, et al. Updating the American Society of Clinical Oncology Value Framework: Revisions and reflections in response to comments Received. J Clin Oncol. May 31,2016.
18-Cherny NI, Dafni U, Bogaerts J, et al. ESMO-Magnitude of Clinical Benefit Scale version 1.1. Ann Oncol. 2017;28(10):2340- 2366. doi:10.1093/annonc/mdx310PubMedGoogle ScholarCrossref
19-Cherny NI, Sullivan R, Dafni U, et al. A standardized, generic, validated approach to stratify the magnitude of clinical benefit that can be anticipated from anti-cancer therapies. The European Society for Medical Oncology: magnitude of clinical benefit scale (ESM-MCBS): Oxford University Press; 2015.
20- Guirgis HM, The impact of PD-L1 on survival and value of the immune check point inhibitors in non-small-cell lung cancer; proposal, policies, and perspective. J ImmunoTherapy of Cancer, February 2018. https://doi.org/10.1186/s40425-018-0320-3
21-Wong W, Kuntz G, Zon RT, et al. Recommendations for enhancing the value of clinical pathways: Findings from the 2020 care pathways working group. JCP, 36-37, November 2021.
22-Husereau D, Drummond M, Petrou S, et al. Consolidated-health-economic-evaluation-reporting-standards-(cheers)-explanation-and-elaboration.Value Health.2013;16 (2):231-250.
23-Siegel JE, Weinstein MC, Russell LB, et al. Panel on cost-effectiveness in health and medicine. Recommendations for reporting cost effectiveness analyses. JAMA. 1996;276(16):1339–1341.
24- Guirgis, HM. Costs of Extended Use of the Immune Check Point Inhibitors in 1st -line Non-Small Cell Lung Cancer. JPO, 34-37, Dec 2021.
25-Paz-Arez L, de Marinis F, Dediu M, et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced non-squamous non-small-cell lung cancer. J Clin Oncol. 2013;31(23):2895-2902. doi:10.1200
26-Chaft JE. Neoadjuvant and Adjuvant Approaches in Surgically Resectable NSCLC. Clinical advances in Hematology and Oncology 19, issue 10, 631-633, October 2021
27-Forde PM, et al. Benefit of neoadjuvant Nivolumab and chemo vs chemo in resectable NSCLC, CheckMate 816. Abstract CT003, Presented at AACR, April 10-15, 2021
28- U.S. Food and Drug Administration Approves Opdivo (nivolumab) with Chemotherapy as Neoadjuvant Treatment for Certain Adult Patients with Resectable Non-Small Cell Lung Cancer. News release. Bristol Myers Squibb. March 4, 2022. Accessed March 4, 2022. https://bit.ly/3INrdQA
29-Aadel A, Chaudelhuri at al. ctDNA in localized lung cancer. Cancer Discover 2017,7:1394-1403
30-Berkemeier F, Whaley C, Robinson JC. Increasing divergence in drug prices between the United States and Germany after implementation of comparative effectiveness analysis and 20 collective price negotiations. J Manag Care Spec Pharm 2019; 25:1310-1317.
31-Robinson JC, Ex P, Panteli D. How drug prices are negotiated in Germany. New York: Commonwealth Fund, June 13, 2019 (https://www.commonwealthfund.org/blog/2019/how-drug-pricesare-negotiated-germany.
32-Kline RK. Bundled Payment Models in Oncology: Learning to Think in New Ways DOI: 10.1200/OP.20.00735 JCO Oncology Practice, Published online February 04, 2021, PMID: 33539197
33-Guirgis, HM. Costs of extended immune check point inhibitors treatment in advanced/metastatic lung cancer: Bundling of cost proposal. ASCO May-June 2020 annual meeting, Chicago, abstract 291815.