Challenges to the current development of fixed-dose antitumor drug combinations

doi:10.19803/j.1672-8629.20240274

Abstract

Abstract: Objective To summarize the characteristics of fixed-dose combinations in the development of antitumor drugs so as to provide references for the development of related combinations. Methods By searching for relevant literature from domestic and overseas databases, the marketed fixed-dose antitumor drug combinations and combination therapies approved by the US FDA in the past three years were analyzed. Results The marketed fixed-dose antitumor drug combinations could significantly improve the therapeutic effects of drugs, improve patient compliance and reduce drug toxicity through multi-target synergistic effects or by improving drug delivery routes. Conclusion Fixed-dose antitumor drug combinations enjoy significant advantages in clinic but still face many challenges in the course of development. In the future, artificial intelligence can provide strong technical support and innovation incentives for the development of drugs.

Key words: combination drug, tumor therapy, multi-target, combination regimen, drug development

CLC Number:

R916
R979.1

JIANG Haiyan, ZHOU Tianyu, FAN Xiaoyu, LI Wanfang, BAO Jie, JIN Hongtao. Challenges to the current development of fixed-dose antitumor drug combinations[J]. Chinese Journal of Pharmacovigilance, 2024, 21(9): 961-966.

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URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20240274

https://zgywjj.magtechjournal.com/EN/Y2024/V21/I9/961

References

[1] LUO GA, LIANG QL, LIU QF, et al.Prospect on the composite drugs innovation system[J]. World Science and Technology-Modernization of Traditional Chinese Medicine(世界科学技术-中医药现代化), 2009, 11(1): 3-10.
[2] YUAN BX, CHEN LN, WANG B.Strategy of fixed-dose combination innovative development[J]. Chinese Journal of Clinical Pharmacology and Therapeutics(中国临床药理学与治疗学), 2013, 18(10): 1175-1181.
[3] YAO W, WAN Z.Clinical research progress and application prospect of polypill[J]. Chinese Journal of Evidence-Based Cardiovascular Medicine(中国循证心血管医学杂志), 2012, 4(6): 491-493.
[4] WU MY, XU W, WANG HY.Dosage regimen selection and application for monoclonal antibody in oncology[J]. The Chinese Journal of Clinical Pharmacology(中国临床药理学杂志), 2019, 35(19): 2471-2475.
[5] QIAN SY, KANG CL.Consideration about compound medicine[J]. The Chinese Journal of Clinical Pharmacology(中国临床药理学杂志), 2015, 31(13): 1335-1337.
[6] PAIK J.Nivolumab plus relatlimab: first approval[J]. Drugs, 2022, 82(8): 925-931.
[7] AGGARWAL V, WORKMAN CJ, VIGNALI DAA.LAG-3 as the third checkpoint inhibitor[J]. Nat Immunol, 2023, 24(9): 1415-1422.
[8] CHI KN, RATHKOPF D, SMITH MR, et al.Niraparib and abiraterone acetate for metastatic castration-resistant prostate cancer[J]. J Clin Oncol, 2023, 41(18): 3339-3351.
[9] MAYER RJ, VAN CUTSEM E, FALCONE A, et al.Randomized trial of TAS-102 for refractory metastatic colorectal cancer[J]. NEngl J Med, 2015, 372(20): 1909-1919.
[10] CHIDA K, KOTANI D, NAKAMURA Y, et al.Efficacy and safety of trifluridine/tipiracil plus bevacizumab and trifluridine/tipiracil or regorafenib monotherapy for chemorefractory metastatic colorectal cancer: a retrospective study[J]. Ther Adv Med Oncol, 2021, 13: 17588359211009143.
[11] HUGHES MS, LENTZSCH S.Safety and efficacy of subcutaneous daratumumab in systemic AL amyloidosis[J]. Ther Clin Risk Manag, 2023, 19: 1063-1074.
[12] TAN AR, IM SA, MATTAR A, et al.Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non-inferiority, phase 3 study[J]. Lancet Oncol, 2021, 22(1): 85-97.
[13] RINI BI, SIGNORETTI S, CHOUEIRI TK, et al.Long-term outcomes with nivolumab plus ipilimumab versus sunitinib in first-line treatment of patients with advanced sarcomatoid renal cell carcinoma[J]. J Immunother Cancer, 2022, 10(12): e005445.
[14] TYKODI SS, GORDAN LN, ALTER RS, et al.Safety and efficacy of nivolumab plus ipilimumab in patients with advanced non-clear cell renal cell carcinoma: results from the phase 3b/4 CheckMate 920 trial[J]. J Immunother Cancer, 2022, 10(2): e003844.
[15] ABEDI KB, ABBASI A, GHASEMI DN, et al.Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): a new era in tumor immunotherapy[J]. Int Immunopharmacol, 2022, 113(Pt A): 109365.
[16] NIKOO M, RABIEE F, MOHEBBI H, et al.Nivolumab plus ipilimumab combination therapy in cancer: current evidence to date[J]. Int Immunopharmacol, 2023, 117: 109881.
[17] LU L, ZHAN M, LI XY, et al.Clinically approved combination immunotherapy: current status, limitations, and future perspective[J]. Curr Res Immunol, 2022, 3: 118-127.
[18] LEE WS, YANG H, CHON HJ, et al.Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity[J]. Exp Mol Med, 2020, 52(9): 1475-1485.
[19] ALLEN E, JABOUILLE A, RIVERA LB, et al. Combined antiangiogenic and anti-PD-L1 therapy stimulates tumor immunity through HEV formation[J]. Sci Transl Med, 2017, 9(385): eaak9679.
[20] LORD CJ, ASHWORTH A.PARP inhibitors: synthetic lethality in the clinic[J]. Science(New York, NY), 2017, 355(6330): 1152-1158.
[21] LIU JF, BARRY WT, BIRRER M, et al.Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study[J]. Lancet Oncol, 2014, 15(11): 1207-1214.
[22] LIU JF, BRADY MF, MATULONIS UA, et al.Olaparib with or without cediranib versus platinum-based chemotherapy in recurrent platinum-sensitive ovarian cancer (NRG-GY004): a randomized, open-label, phase III trial[J]. J Clin Oncol, 2022, 40(19): 2138-2147.
[23] PENSON RT, VALENCIA RV, CIBULA D, et al.Olaparib versus nonplatinum chemotherapy in patients with platinum-sensitive relapsed ovarian cancer and a germline BRCA1/2 mutation (SOLO3): a randomized phase III trial[J]. J Clin Oncol, 2020, 38(11): 1164-1174.
[24] JANCZURA M, SIP S, CIELECKA-PIONTEK J.The development of innovative dosage forms of the fixed-dose combination of active pharmaceutical ingredients[J]. Pharmaceutics, 2022, 14(4): 834.
[25] GOYANES A, DET-AMORNRAT U, WANG J, et al.3D scanning and 3D printing as innovative technologies for fabricating personalized topical drug delivery systems[J]. J Control Release, 2016, 234: 41-48.
[26] PIETRZAK K, ISREB A, ALHNAN MA.A flexible-dose dispenser for immediate and extended release 3D printed tablets[J]. Eur J Pharm Biopharm, 2015, 96: 380-387.
[27] KUENZI BM, PARK J, FONG SH, et al.Predicting drug response and synergy using a deep learning model of human cancer cells[J]. Cancer Cell, 2020, 38(5): 672-684.
[28] YANG J, XU Z, WU WKK, et al.GraphSynergy: a network-inspired deep learning model for anticancer drug combination prediction[J]. J Am Med Inform Assoc, 2021, 28(11): 2336-2345.