The New Frontier of Low-Cost Neoadjuvant Therapy

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Published Aug 30, 2023
DOI: https://doi.org/10.18103/mra.v11i8.4313

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Main Article Content

Helmy M. Guirgis
University of California-Irvine, Orange, CA

Abstract

Background: We previously reported that the 2-year costs of the immune check inhibitors (ICI) were equitable with outcomes. Extended use multiplied costs. Nivolumab neoadjuvant plus chemotherapy improved event-free survival in early resectable lung cancer at low cost. Neoadjuvant is a novel advance in earlier cancer treatment. The targeted therapy Osimertinib is currently utilized as neoadjuvant, adjuvant and in advanced/metastatic lung cancer with cost increasing yearly with further use. We aimed to quantify the cost and savings of ICI and targeted therapy in earlier vs advanced cancer stages in multiple solid tumors.


Methods: Annual 2019-2020 costs of Osimertinib were calculated ad monthly optimal dose x 12. Costs of ICI were calculated as dose x mg/m2 or per 80 kg x price x number of cycles per year.


Results: The 2-year Osimertinib cost in metastatic disease was $496,744, adjuvant 1-year $248,372 and neoadjuvant $31,046. Estimated neoadjuvant cost savings over 1-year were $217,326.


Pembrolizumab $134,796 annual cost was the median of 5- evaluated ICI. It is used as adjuvant at half the 2-year cost. Extended therapy by 6-12 months, beyond the 2-year approval, added an extra $67,398-$134,796.


Durvalumab following chemo-radiation, (Pacific) was approved in unresectable stage III NSCLC x 1-year at $148,007, saving a 2nd year-cost. Adjuvant Atezolizumab 1-year cost in 1st-line was $124,761. Approval was based on improving the disease-free survival using 4 cycles + chemo in resected stage II-IIIA lung (Impower010), Cost was $35,644 cost with $89,117 savings.


In the neoadjuvant space, Nivolumab + chemotherapy improved event-free survival in resectable lung cancer (Forde, 2022) at $31,425, saving $137,423. In early-stage triple negative breast cancer (GeparoNuevo-NCTO2685059), 8-cycle Durvalumab prolonged survival at $45,464. Cemiplimab x 4-cycle in stage II to IV, cutaneous squamous-cell carcinoma resulted in complete pathological response (Gross, 2022) at $35,652 vs 1-year $125,108. In early colorectal cancer (NICHE-2), 2-cycle Nivolumab plus 1- low-dose Ipilimumab followed by surgery resulted in major pathological response at $24,927.


Conclusions: Neoadjuvant Osimertinib and ICI cost a small fraction resulting in significant savings in early-stage lung cancer treatment. Cost advantages in other solid tumors warrant further confirmation.

Keywords: Costs, non-small lung cell cancer, Immune check point inhibitors, Adjuvant, Neoadjuvant

Article Details

How to Cite
GUIRGIS, Helmy M.. The New Frontier of Low-Cost Neoadjuvant Therapy. Medical Research Archives, [S.l.], v. 11, n. 8, aug. 2023. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4313>. Date accessed: 13 may 2024. doi: https://doi.org/10.18103/mra.v11i8.4313.
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Issue
Vol 11 No 8 (2023): August Issue, Vol.11, Issue 8
Section
Research Articles

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References

1. Guirgis, HM. The Impact of The Immune Check Point on Cost in Lung Cancer: Duration of use. ESMED, July 31, 2022. Medical Research Archives, [online] 10(7). https://doi.org/10.18103/mra. v10i7.2859. ISSN: 2375-1924.
2. 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.
3. 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.
4. Guirgis, Helmy M. Target Therapy vs the Immune Check Point Inhibitors in Lung Cancer: Costs and Caps Platform. ESMED February 2023.
5. 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
6. 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.
7. 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.
8. Reck M, Ciuleanu TE, Cobo Dols M, et al. Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (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.
9. 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
10. Herbst RS, Gluseppe G, de Marinis F, et al, Atezolizumab for First-Line Treatment of PD-L1–Selected Patients with NSCLC. N Engl J Med. 383,1328-1339. 2020.
11. Long GV, Luke JJ, Khattak MA, et al. Pembrolizumab versus placebo as adjuvant therapy in resected IIb or IIc melanoma (KEYNOTE-716): distant metastasis-free survival results of a multicentre, double blind, randomized 3 trial. Lancet Oncol, 10,1379-
1387, November 2023.
12. Choueiri TK, Piotr, Park SH et al. Pembrolizumab versus placebo as post nephrectomy adjuvant therapy for patients with renal cell carcinoma: Randomized, double-blind, phase III KEYNOTE-564 study. ASCO annual meeting 2019: LBAS, available online August 2022.
13. Forde PM, Spicer J, Lu S et al. Neoadjuvant Nivolumab plus chemotherapy in resectable lung cancer. N Engl J med. April 2022. 10.doi 10.1056/NEJMoa2202170
14. Rosner S. et al. Neoadjuvant 2-Nivo-cycles in patients with stage 1 to IIIA NSCLC 4-weeks before surgery. Clinical cancer research, 2023.
15. Loibi S, Schneeweiss A, Huober J, et al. Neoadjuvant Durvalumab Improves Survival in Early Triple-negative Breast Cancer Independent of Pathological Complete Response. Annal of Oncology, available online 9 August 2022.
16. 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, 2021.
17. Gross ND, Miller DM, Khushalani NI et al., Neoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell carcinoma. N Engl J Med, 387:1557-1568, 2022. DOI: 10.1056/NEJMoa2209813.
18. Chalabi M, et al. Neoadjuvant Nivolumab and Ipilimumab in early-stage resectable colon cancer (NICHE-2). The European Society of Medical Oncology Congress 2022.
19. Hao Z, Parasramka S, Chem Q, et al. Neoadjuvant chemotherapy for resectable metastatic colon cancer in non-academic and academic programs. The Oncologist 28, 48-58, 2023.
20. Liu Y, Fan L, Wang Zhong-Hua, Shao Zhi-Ming, et al. Nab-paclitaxel followed by dose dense Epirubicin/cyclophosphamide in neoadjuvant chemotherapy for triple negative breast cancer: A phase II study. The Oncologist 28, 80-e76, 2023.
21. 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, 2022.
22. 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
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. Wakelee HA, Altorki NK, Zhoe C et al. Impower010: Primary results of a III global study of atezolizumab in addition to chemo versus best supportive care in resected IB-IIIA non-small cell lung cancer (NSCLC)(ASCO), Abstract 8500: J Clin Onc.2021:39 (15) (suppl),17- 14, 2021, World Conference om lung cancer (WCLC 2021).
29. Wakelee HA, Liberman M, Kato T, et al: KEYNOTE-671: Randomized, double-blind, phase 3 study of pembrolizumab or placebo plus platinum-based chemotherapy followed by resection and pembrolizumab or placebo for early-stage NSCLC. 2023 ASCO Annual Meeting. Abstract LBA100. Presented June 3, 2023.