Reducing Financial Toxicity in Lung Cancer Therapy
Reducing the Financial Toxicity of Prolonged Therapy in Advanced/Metastatic Lung Cancer, Saving Methodology
Helmy M Guirgis1
- University of California, Irvine
OPEN ACCESS
PUBLISHED: 31 July 2024
CITATION: Guirgis, HM., 2024. Reducing the Financial Toxicity of Prolonged Therapy in Advanced/Metastatic Lung Cancer, Saving Methodology. Medical Research Archives, [online] 12(7). https://doi.org/10.18103/mra.v12i7.5558
COPYRIGHT: © 2024 European Society of Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI https://doi.org/10.18103/mra.v12i7.5558
ISSN 2375-1924
ABSTRACT
Introduction: Value of the monoclonal antibodies and targeted therapy have been extensively addressed in advanced/metastatic non-small cell lung cancer (a/d-NSCLC). Costs, however, have largely been overlooked. The monoclonal antibodies (MABs) were approved at 2-year- overall survival. Targeted therapy (TT), approved at 2-3-year-survival, are currently continued as long as efficacious and safe. Drug costs were proportional to duration of therapy (Guirgis, ESMED, 2024). Previous attempts to control the high cost of anticancer drugs including cap-imposed limits have failed. There is a pressing need for cost cutting and saving methodology that is fair, voluntary and equitable for both patients and pharma. Our goals in a/d-NSCLC: A- Demonstrate the unnecessarily high cost of 3rd year MABs. B- Pay in full the 1st- TT 3-year-costs but reduce by 50% the 4th year and throughout the entire course.
Methods: MABs costs were calculated as dose in mg x United States price x number of years and TT as the monthly optimal dose x 12 x duration of use.
Results: The median yearly cost of 5-MABs was $163,640. In view of overall survival outcome, the 2-year $327,2802 cost was justified. However, the 3-year $490,920 cost was unjustified due to lack of further survival improvement. The annual TT median cost was $229,600, 4- years $918,400 and the 10-years $2,296,000. Treatment of 1,000 patients in the United States by all TT for 4-years would cost $918,400,000 and in Europe 2,000 patients would mount to $1,836,800,000. Costs continue to climb up with every extended year. Applying a 50% reduction to the 4th year of $229,600, the potential saving was $114,800. The 4-year total payments would be $229,600 x 3 + $114,800 = $803,600, instead of $918,400. The 10-year $2,296,000 cost would drop to $1,492,400.
Conclusion: In a/d-NSCLC, a 3rd year-MABs cost was considered unnecessary due to lack of further survival improvement. A 50% reduction of TT annual costs beginning the 4th-year and throughout the entire course would avoid the heavy financial toxicity of prolonged use.
Keywords
advanced lung cancer, financial toxicity, monoclonal antibodies, targeted therapy, cost reduction
Introduction
We previously reported the case of 65 yo female who presented in 2014 with advanced/metastatic non-small cell lung cancer (a/d-NSCLC) and anaplastic lymphoma kinase (ALK+). She was successfully treated by the 2nd generation Alectinib 600 mg po bid daily (1). The approximate 10-year estimated cost was $2,211,100. Targeted Therapy (TT) are approved after 2-3-year-trials. Use is currently continued as long as effective and safe. However, such policy is currently debated. The monoclonal antibodies (MABs) were approved at 2-year overall survival. Costs were proportional to number of purchases and/or duration of use (2). Previous attempts to control the high cost of anticancer drugs including cap-imposed limits have failed. The high costs of prolonged use of both MABs and TT prompted the present investigation. We purposed to quantify in a/d-NSCLC: 1- The unnecessarily high cost of MABs 3rd year. 2 –Pay in full the 1st 3-years TT costs but reduce by 50% the 4th -year and throughout the entire treatment 3- Quantify the cost savings based on our proposal.
Methods: MABs costs were calculated as dose in mg x posted price x number of years and TT as the monthly optimal dose x 12 x number of years use.
Results
The 5-MABs (3-7) median annual cost was $163,640, (Table 1). The 3rd year costs were unjustified due to lack of further survival improvement. Osimertinib, approved as neoadjuvant, adjuvant and in metastatic disease (8,9), had an annual $229,600 cost and was the median of 5-TT. Costs increased with every year of further use. At present, proper Identification of genomic marker aberrations is crucial in the proper and order of therapy. The price tag of 2-3-tests of a reliable wide spectrum marker was estimated at $2,000. The 3-year TT $688,800 costs seemed reasonable in view of the reported value and ought to be fully paid. However, the 4-year $918,400 costs were considered excessive. We reasoned that if 1,000 American patients were treated by TT at $229,600 for 4-years, the cost would mount to $918,400,000. The 10-year cost would be $2,296,000. In Europe, treating 2,000 patients would cost $4,592,000. A 50% reduction applied only to year 4th year would save $114,800. The 4-year total would be $918,400 – $114,800 = $803,600. The 10-year would drop from $2,296,000 to $1,492,400, resulting in potential $803,600 savings.
Table 1 demonstrates comparison between chemo and various tyrosine kinase inhibitors. Deucravacitinib (10,11) was included to demonstrate its use and cost in non-cancer indication. It has wider application in moderate-severe plaque psoriasis. Osimertinib, Alectinib, Selpercatinib (12) and Repotrectinib (13) are widely used in a/d-NSCLC.
| Drug | 2-year Costs | 3-year Costs |
|---|---|---|
| Pembrolizumab | $380,800 | $571,200 |
| Durvalumab | $327,280 | $490,920 |
| Atezolizumab | $305,340 | $458,010 |
| Nivolumab | $404,660 | $606,990 |
| Cemiplimab | $295,040 | $442,560 |
With no evidence of overall survival improvement after 2-years, the 3-year- MABs cost was considered unnecessary.
| Drugs and Doses | Annual Costs |
|---|---|
| Generic Chemo | $1,000 |
| Alectinib (1) 600 bid po | $221,110 |
| Osimertinib 80 mg once daily + chemo (8,9) | $230,600 |
| Deucravacitinib, Tyrosine Kinase 2 (TYK2), 6.0 mg po once daily (non-cancer drug) (10,11) | $82,680 |
| Selpercatinib (12) 120-160 mg bid | $271,164 |
| Repotrectinib (Trident -1 trial) (13) 160 mg bid | Negotiable, varying from $159,984-$364,032 |
All the above drugs were approved and utilized in the US, Canada, European Nations, and Japan. The 2-3-year $688,800 TT costs seemed reasonable in view of the reported outcome and ought to be fully paid. However, the 4-year $918,400 costs were considered excessive. We reasoned that if 1,000 American patients were treated by TT at $229,600 for 4-years, the cost would mount to $918,400,000. The 10-year cost would be $2,296,000. In Europe, treating 2,000 patients would cost $4,592,000. The potential cost savings were summarized in Table 3.
| Costs | 1st to 3rd year | 4th year | 4,5,6 total costs | 4-10 total costs |
|---|---|---|---|---|
| Current Annual Costs | $204,000 | $204,000 | $812,000 | $1,428,000 |
| Proposed 50% cost reduction starting the 4th year | $204,000 | $102,000 | $406,000 | $714,000 |
Discussion
Development of a new cancer therapy from inception to delivery takes an years of ingenuity, hard work, and strong financial backing. Pharma needs to be compensated for such sacrificial endeavors. At present, value, and cost effectiveness (14-16) of cancer drugs are calculated and documented before or soon after drug efficacy and safety approval. Reports on cancer drug costs are currently scanty and generally labelled excessive. Utilization, if any, is rare by nations and patients with limited resources. Admittedly, costs are negotiable, and the subject is indeed sensitive. Cap-imposed limits have been proposed but received minimal acceptable (17,18). The painful financial toxicity of oral anti-cancer drugs has been clearly outlined (19,20). Pharma is unlikely to sponsor cost cancer studies, leaving the academic intuitions to carry out this delicate task. At present, proper Identification of genomic marker aberrations is crucial in the proper and order of therapy. The estimated at $2,000 price tag of 2-3-tests of a reliable wide spectrum marker was undeniably worthy it. The 2-year overall survival of MABs have been well-defined in a/d- NSCLC with programmed death ligand 1 (PD-L1) expression at 50% and above (3-7). Some oncologists and patients continue therapy for a third year. Such cost was considered unnecessary due to lack of further survival improvement.
The terminology of all TT ends in “nibs”, and hence referred at times as “NIBs”. They belong to the tyrosine kinase inhibitors family. Osimertinib is a prototype and antagonist of epidermal growth factor (EGFR). The drug was originally planned to treat T7M mutations, but presently used to prevent the potential development of such mutations. The U.S. Food and Drug Administration (FDA) has recently approved Osimertinib with platinum-based chemotherapy for patients with a/d-NSCLC and no prior systemic therapy for tumors with EGFR exon 19 deletions or exon 21 L858R mutations (FLAURA2): clinical validation through TRIDENT-1 Trial (NCT03093116). Other TT followed Osimertinib including Alectinib (1), Selpercatinib (13) in RET aberrations with up to 2.0% incidence and Repotrectinib (14) with ROS1 Fusions with 1.0-2.0 %. Many other genomic alterations are presently targetable.
Access to financial assistance programs and their impact on the overall spending on oral anticancer medications has been recently described (21). For patients and countries with limited resources, TT use at any duration is essentially unaffordable. In the US and Europe, treatment of few thousand patients for 10 years is economically burdensome and could divert finances resources from other health expenditures e.g. vaccines and other essentials. The Canadian health system demonstrated the rapid rising costs of cancer medicines (22). The wide difference in Repotrectinib costs from $159,984-$364,032 clearly affirm the variation in cancer drugs prices and the need for negotiation and reduction. The present work takes a step further, focusing on and pointing to the prolonged therapy as the core underlying problem.
In summary, safe, and effective cancer care (23), with affordable cancer drugs are worthy goals to pursue and attain. Previous attempts to control the high costs of anti-cancer drugs have failed. Proper Identification of genomic marker aberrations is crucial for appropriate and successful cost-management. The estimated $2,000 costs for 2-3-tests of a reliable wide spectrum marker were worthy of the price tag. Currently, continued TT costs are too high to sustain. A 50% TT cost reduction at 4-10-year is even-handed and win-win for 1- Patients buying at reduced costs 2- Pharma enjoying wider sales. The cost-reduction approach is simple, direct, voluntary and most of all, not requiring approval of any clinical trial.
References
1. Guirgis, H, Cost matters. journal of Cancer & Oncology (OAJCO) Commentary Volume 7 Issue 1, April 19, 2023. doi: 10.23880/oajco-16000184.
2. Guirgis. HM. Costs of Target Therapy and Proportionality to Number of Purchases: Propose Using Maintenance Dose and Limited Duration. ESMED 2024. doi: https://doi.org/10.18103/mra.v12i1.4959.ISSN:2375-1924.
3. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small cell lung cancer. N Engl J Med. 372:2018–28, 2015.
4. Reck M, Rodriguez-Abreu D, Robinson AG, et al. Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med. 375:823–1833, 2016.
5. Herbst RS, Baas P, Kim D-W, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-postive, advanced non-small-cell lung cancer (KEYNOTE -010): A randomised controlled trial. Lancet 387: 1540-1550, 2016.
6. Herbst RS, Gluseppe G, de Marinis F, et al. Atezolizumab for First-Line Treatment of PD pharma-L1–Selected Patients with NSCLC. N Engl J Med. 383,1328-1339. 2020.
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. 397(10274): 592-604.
8. Herbest RS, Wu Yi-long, John T, Adjuvant Osimertinib for Resected EGFR-Mutated Stage IB-IIIA Non–Small-Cell Lung Cancer: Updated Results from the Phase III Randomized ADAURA Trial, J Clin Oncol, 2023 Jan 31; JCO2202186. doi: 10.1200/JCO.22.02186.
9. Lv C, Fang W, Wu N, et al. Osimertinib as Neoadjuvant Therapy for EGFR-Mutant Resectable Stage II-IIIB Lung Adenocarcinoma. Lung Cancer; 2023 Feb 17; 178,151-156.
10. Chimalakonda A, Burke J, Cheng L, et al. Selectivity profile of the tyrosine kinase 2 inhibitor deucravacitinib compared with janus kinase 1/2/3 inhibitors. Dermatol Ther (Heidelb) 2021;11(5):1763–1776. doi: 10.1007/s13555-021-00596-8.
11. Armstrong AW, Mehta MD, Schupp CW, et al. Psoriasis prevalence in adults in the United States. JAMA Dermatol. Published online June 30, 2021. doi:10.1001/jamadermatol.2021.2007.
12. Drilon A, Oxnard GR, Daniel SW et al. Efficacy of Selpercatinib in RET Fusion–Positive Non–Small-Cell Lung Cancer. N Engl J Med 2020; 383:813-824 doi: 10.1056/NEJMoa2005653.
13. Drilon A, Camidge DR, Lin JJ, et al. Repotrectinib in ROS1 Fusion–Positive Non–Small-Cell Lung Cancer. N Engl J Med 2024; 390:118-131. doi: 10.1056/NEJMoa2302299.
14. 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.
15. 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.
16. Siegel JE, Weinstein MC, Russell LB, et al. Panel on cost-effectiveness in health and medicine. Recommendations for reporting cost effectiveness analyses. JAMA. 276(16):1339–1341,1996.
17. 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.
18. 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.
19. Li M, Liao K, Pan I-Wen et al. Growing Financial burden from high cost targeted oral anticancer medicines among Medicare beneficiaries with cancer. JCO oncology practice ,18,11,759, 2002.
20. Peppercorn, J. The impact of financial toxicity on cancer care. Clin adv, Hem & Onc. 21, October 2023.
21. Ragavan MV, Swartz S, Clark M, et al. Access to financial assistance programs and their impact on overall spending on oral anticancer medications at an integrated specialty pharmacy. Ascopubs.org/journal/op, 20 February 2024.
22. The lancet Oncology. Safe and effective cancer care: how long must we wait? Editorial, 25, March 2024.
23. Del Paggio JC, Naipaul R, Gavura S, et al. Cost and value of cancer medicines in a single-payer public health system in Ontario, Canada: a cross-sectional study. www.thelancet.com/oncology, vol 25, April 2024.