Skip to content
2000
Volume 25, Issue 7
  • ISSN: 1568-0096
  • E-ISSN: 1873-5576

Abstract

Background

Non-small cell lung cancer (NSCLC) predominantly affects older adults; these patients have significant comorbidities, making them unsuitable for chemotherapy. This study aimed to evaluate the efficacy and safety of immune checkpoint inhibitor (ICI) along with anlotinib combination therapy as a first-line treatment in older NSCLC patients with programmed death ligand-1(PD-L1) expression<50%.

Methods

We conducted a retrospective observational study including 73 patients with advanced NSCLC treated at Nanjing Brain Hospital. All patients were aged 75 years or older and received first-line systemic therapy with a combination of PD-1 inhibitors and anlotinib. Clinical data were obtained from electronic medical records and analyzed through Kaplan-Meier estimates and Cox proportional hazards models to assess progression-free survival (PFS), overall survival (OS), and the influence of different variables.

Results

The patients had a median age of 80 years. The median PFS was 9.8 months (95% CI: 7.9-11.7), and the median OS was 19.5 months (95% CI: 17.3-21.7). PD-L1 tumor proportion score (TPS) <1% (χ2=10.263, P=0.001) and absence of treatment-induced hypertension (χ2=12.804, P<0.001) were identified as independent risk factors for poor PFS. Advanced disease stage (χ2=11.900, P=0.001), PD-L1 TPS <1% (χ2=6.643, P=0.010), and having two or more chronic comorbidities (χ2=9.011, P=0.003) were independent risk factors for poor OS. Treatment-related hypertension was observed in 25% of patients and was associated with better PFS.

Conclusion

ICI-anlotinib combination therapy showed promising efficacy and an acceptable safety profile in older NSCLC patients. Future studies involving larger populations are necessary to validate these findings and determine the potential of PD-L1 levels as a biomarker for treatment stratification.

Loading

Article metrics loading...

/content/journals/ccdt/10.2174/0115680096364469250113105648
2025-01-21
2025-10-11
Loading full text...

Full text loading...

References

  1. MillerK.D. NogueiraL. DevasiaT. MariottoA.B. YabroffK.R. JemalA. KramerJ. SiegelR.L. Cancer treatment and survivorship statistics, 2022.CA Cancer J. Clin.202272540943610.3322/caac.21731 35736631
    [Google Scholar]
  2. ZhangJ. ZhaoL. LiH. JiaY. KongF. Immunosenescence and immunotherapy in older NSCLC patients.J. Cancer Res. Ther.202420191610.4103/jcrt.jcrt_1523_23 38554292
    [Google Scholar]
  3. SinghH. BeaverJ.A. KimG. PazdurR. Enrollment of older adults on oncology trials: An FDA perspective.J. Geriatr. Oncol.20178314915010.1016/j.jgo.2016.11.001 28017686
    [Google Scholar]
  4. ScherK.S. HurriaA. Under-representation of older adults in cancer registration trials: known problem, little progress.J. Clin. Oncol.201230172036203810.1200/JCO.2012.41.6727 22547597
    [Google Scholar]
  5. BorghaeiH. Paz-AresL. HornL. SpigelD.R. SteinsM. ReadyN.E. ChowL.Q. VokesE.E. FelipE. HolgadoE. BarlesiF. KohlhäuflM. ArrietaO. BurgioM.A. FayetteJ. LenaH. PoddubskayaE. GerberD.E. GettingerS.N. RudinC.M. RizviN. CrinòL. BlumenscheinG.R.Jr AntoniaS.J. DorangeC. HarbisonC.T. Graf FinckensteinF. BrahmerJ.R. Nivolumab versus docetaxel in advanced nonsquamous non–small-cell lung cancer.N. Engl. J. Med.2015373171627163910.1056/NEJMoa1507643 26412456
    [Google Scholar]
  6. GaronE.B. RizviN.A. HuiR. LeighlN. BalmanoukianA.S. EderJ.P. PatnaikA. AggarwalC. GubensM. HornL. CarcerenyE. AhnM.J. FelipE. LeeJ.S. HellmannM.D. HamidO. GoldmanJ.W. SoriaJ.C. Dolled-FilhartM. RutledgeR.Z. ZhangJ. LuncefordJ.K. RangwalaR. LubinieckiG.M. RoachC. EmancipatorK. GandhiL. Pembrolizumab for the treatment of non-small-cell lung cancer.N. Engl. J. Med.2015372212018202810.1056/NEJMoa1501824 25891174
    [Google Scholar]
  7. HerbstR.S. GiacconeG. de MarinisF. ReinmuthN. VergnenegreA. BarriosC.H. MoriseM. FelipE. AndricZ. GeaterS. ÖzgüroğluM. ZouW. SandlerA. EnquistI. KomatsubaraK. DengY. KurikiH. WenX. McClelandM. MocciS. JassemJ. SpigelD.R. Atezolizumab for first-line treatment of PD-l1–selected patients with NSCLC.N. Engl. J. Med.2020383141328133910.1056/NEJMoa1917346 32997907
    [Google Scholar]
  8. HerbstR.S. BaasP. KimD.W. FelipE. Pérez-GraciaJ.L. HanJ.Y. MolinaJ. KimJ.H. ArvisC.D. AhnM.J. MajemM. FidlerM.J. de CastroG.Jr GarridoM. LubinieckiG.M. ShentuY. Im, E.; Dolled-Filhart, M.; Garon, E.B. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial.Lancet2016387100271540155010.1016/S0140‑6736(15)01281‑7 26712084
    [Google Scholar]
  9. NosakiK. SakaH. HosomiY. BaasP. de CastroG.Jr ReckM. WuY.L. BrahmerJ.R. FelipE. SawadaT. NoguchiK. HanS.R. PiperdiB. KushD.A. LopesG. Safety and efficacy of pembrolizumab monotherapy in elderly patients with PD-L1–positive advanced non–small-cell lung cancer: Pooled analysis from the KEYNOTE-010, KEYNOTE-024, and KEYNOTE-042 studies.Lung Cancer201913518819510.1016/j.lungcan.2019.07.004 31446994
    [Google Scholar]
  10. TakamoriS. ShimokawaM. KomiyaT. Prognostic impact of chronological age on efficacy of immune checkpoint inhibitors in non‐small‐cell lung cancer: Real‐world data from 86 173 patients.Thorac. Cancer202112212943294810.1111/1759‑7714.14178 34612011
    [Google Scholar]
  11. TsukitaY. TozukaT. KushiroK. HosokawaS. SumiT. UematsuM. HonjoO. YamaguchiO. AsaoT. SugisakaJ. SaitoG. ShiiharaJ. MoritaR. KatakuraS. YasudaT. HisakaneK. MiyauchiE. MoritaS. KobayashiK. AsahinaH. Immunotherapy or chemoimmunotherapy in older adults with advanced non–small cell lung cancer.JAMA Oncol.202410443944710.1001/jamaoncol.2023.6277 38451530
    [Google Scholar]
  12. ZhangK. MaX. GaoH. WangH. QinH. YangS. LiuX. Efficacy and safety of anlotinib in advanced non-small cell lung cancer: A real-world study.Cancer Manag. Res.2020123409341710.2147/CMAR.S246000 32494205
    [Google Scholar]
  13. LvB. ChenJ. LiuX.L. Anlotinib-induced hypertension: Current concepts and future prospects.Curr. Pharm. Des.202228321622410.2174/1381612827666211006145141 34620054
    [Google Scholar]
  14. SongY. XiaoJ. FangW. LuP. FanQ. ShuY. FengJ. ZhangS. BaY. ZhaoY. LiuY. BaiC. BaiY. TangY. HeJ. HuangJ. The relationship between treatment-induced hypertension and efficacy of anlotinib in recurrent or metastatic esophageal squamous cell carcinoma.Cancer Biol. Med.202118256256810.20892/j.issn.2095‑3941.2020.0187 33724741
    [Google Scholar]
  15. FukumuraD. KloepperJ. AmoozgarZ. DudaD.G. JainR.K. Enhancing cancer immunotherapy using antiangiogenics: Opportunities and challenges.Nat. Rev. Clin. Oncol.201815532534010.1038/nrclinonc.2018.29 29508855
    [Google Scholar]
  16. KhanK.A. KerbelR.S. Improving immunotherapy outcomes with anti-angiogenic treatments and vice versa.Nat. Rev. Clin. Oncol.201815531032410.1038/nrclinonc.2018.9 29434333
    [Google Scholar]
  17. YiM. JiaoD. QinS. ChuQ. WuK. LiA. Synergistic effect of immune checkpoint blockade and anti-angiogenesis in cancer treatment.Mol. Cancer20191816010.1186/s12943‑019‑0974‑6 30925919
    [Google Scholar]
  18. LeeW.S. YangH. ChonH.J. KimC. Combination of anti-angiogenic therapy and immune checkpoint blockade normalizes vascular-immune crosstalk to potentiate cancer immunity.Exp. Mol. Med.20205291475148510.1038/s12276‑020‑00500‑y 32913278
    [Google Scholar]
  19. FanP. QiangH. LiuZ. ZhaoQ. WangY. LiuT. WangX. ChuT. HuangY. XuW. QinS. Effective low-dose Anlotinib induces long-term tumor vascular normalization and improves anti-PD-1 therapy.Front. Immunol.20221393792410.3389/fimmu.2022.937924 35990640
    [Google Scholar]
  20. FinnR.S. QinS. IkedaM. GalleP.R. DucreuxM. KimT.Y. KudoM. BrederV. MerleP. KasebA.O. LiD. VerretW. XuD.Z. HernandezS. LiuJ. HuangC. MullaS. WangY. LimH.Y. ZhuA.X. ChengA.L. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma.N. Engl. J. Med.2020382201894190510.1056/NEJMoa1915745 32402160
    [Google Scholar]
  21. RiniB.I. PlimackE.R. StusV. GafanovR. HawkinsR. NosovD. PouliotF. AlekseevB. SoulièresD. MelicharB. VynnychenkoI. KryzhanivskaA. BondarenkoI. AzevedoS.J. BorchielliniD. SzczylikC. MarkusM. McDermottR.S. BedkeJ. TartasS. ChangY.H. TamadaS. ShouQ. PeriniR.F. ChenM. AtkinsM.B. PowlesT. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma.N. Engl. J. Med.2019380121116112710.1056/NEJMoa1816714 30779529
    [Google Scholar]
  22. SocinskiM.A. JotteR.M. CappuzzoF. OrlandiF. StroyakovskiyD. NogamiN. Rodríguez-AbreuD. Moro-SibilotD. ThomasC.A. BarlesiF. FinleyG. KelschC. LeeA. ColemanS. DengY. ShenY. KowanetzM. Lopez-ChavezA. SandlerA. ReckM. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC.N. Engl. J. Med.2018378242288230110.1056/NEJMoa1716948 29863955
    [Google Scholar]
  23. DouX.J. MaR.Y. RenD.W. LiuQ. YanP. Effectiveness and safety of anlotinib combined with pd-1 blockades in patients with previously immunotherapy treated advanced non-small cell lung cancer: A retrospective exploratory study.Lung Cancer202415294010.2147/LCTT.S444884 38560413
    [Google Scholar]
  24. ChenS. MoW. JiangW. ZhouS. GanH. YuQ. The benefit and risk of PD-1/PD-L1 inhibitors plus anti-angiogenic agents as second or later-line treatment for patients with advanced non-small-cell lung cancer: A systematic review and single-arm meta-analysis of prospective clinical trials.Front. Immunol.202314121825810.3389/fimmu.2023.1218258 37614237
    [Google Scholar]
  25. World medical association declaration of helsinki: Ethical principles for medical research involving human subjects.JAMA2013310202191219410.1001/jama.2013.281053 24141714
    [Google Scholar]
  26. KempenJ.H. Appropriate use and reporting of uncontrolled case series in the medical literature.Am. J. Ophthalmol.20111511710.e110.1016/j.ajo.2010.08.047 21163373
    [Google Scholar]
  27. PuX. XiaoZ. LiJ. WuZ. MaZ. WengJ. XiaoM. ChenY. CaoY. CaoP. WangQ. XuY. LiK. ChenB. XuF. LiuL. KongY. ZhangH. DuanH. WuL. Anlotinib plus docetaxel vs. docetaxel alone for advanced non-small-cell lung cancer patients who failed first-line treatment: A multicenter, randomized phase II trial.Lung Cancer202419110753810.1016/j.lungcan.2024.107538 38552544
    [Google Scholar]
  28. YuL. XuJ. QiaoR. HanB. ZhongH. ZhongR. Efficacy and safety of anlotinib combined with PD ‐1/PD‐L1 inhibitors as second‐line and subsequent therapy in advanced small‐cell lung cancer.Cancer Med.20231255372538310.1002/cam4.5360 36250532
    [Google Scholar]
  29. YuC. JiangL. YangD. DongX. YuR. YuH. Anlotinib hydrochloride and PD-1 blockade as a salvage second-line treatment in patients with progress of local advanced non-small cell lung cancer in half a year after standard treatment.OncoTargets Ther.2022151221122810.2147/OTT.S380615 36262804
    [Google Scholar]
  30. EisenhauerE.A. TherasseP. BogaertsJ. SchwartzL.H. SargentD. FordR. DanceyJ. ArbuckS. GwytherS. MooneyM. RubinsteinL. ShankarL. DoddL. KaplanR. LacombeD. VerweijJ. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1).Eur. J. Cancer200945222824710.1016/j.ejca.2008.10.026 19097774
    [Google Scholar]
  31. Paz-AresL. CiuleanuT.E. CoboM. SchenkerM. ZurawskiB. MenezesJ. RichardetE. BennounaJ. FelipE. Juan-VidalO. AlexandruA. SakaiH. LinguaA. SalmanP. SouquetP.J. De MarchiP. MartinC. PérolM. ScherpereelA. LuS. JohnT. CarboneD.P. Meadows-ShropshireS. AgrawalS. OukessouA. YanJ. ReckM. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): An international, randomised, open-label, phase 3 trial.Lancet Oncol.202122219821110.1016/S1470‑2045(20)30641‑0 33476593
    [Google Scholar]
  32. BrahmerJ.R. LeeJ.S. CiuleanuT.E. Bernabe CaroR. NishioM. UrbanL. Audigier-ValetteC. LupinacciL. SanghaR. PluzanskiA. BurgersJ. MahaveM. AhmedS. SchoenfeldA.J. Paz-AresL.G. ReckM. BorghaeiH. O’ByrneK.J. GuptaR.G. BushongJ. LiL. BlumS.I. EcclesL.J. RamalingamS.S. Five-Year survival outcomes with nivolumab plus ipilimumab versus chemotherapy as first-line treatment for metastatic non–small-cell lung cancer in checkmate 227.J. Clin. Oncol.20234161200121210.1200/JCO.22.01503 36223558
    [Google Scholar]
  33. Rodríguez-AbreuD. PowellS.F. HochmairM.J. GadgeelS. EstebanE. FelipE. SperanzaG. De AngelisF. DómineM. ChengS.Y. BischoffH.G. PeledN. ReckM. HuiR. GaronE.B. BoyerM. KurataT. YangJ. PietanzaM.C. SouzaF. GarassinoM.C. Pemetrexed plus platinum with or without pembrolizumab in patients with previously untreated metastatic nonsquamous NSCLC: protocol-specified final analysis from KEYNOTE-189.Ann. Oncol.202132788189510.1016/j.annonc.2021.04.008 33894335
    [Google Scholar]
  34. Paz-AresL. VicenteD. TafreshiA. RobinsonA. Soto ParraH. MazièresJ. HermesB. CicinI. MedgyasszayB. Rodríguez-CidJ. OkamotoI. LeeS. RamlauR. VladimirovV. ChengY. DengX. ZhangY. BasT. PiperdiB. HalmosB. A randomized, placebo-controlled trial of pembrolizumab plus chemotherapy in patients with metastatic squamous NSCLC: Protocol-specified final analysis of KEYNOTE-407.J. Thorac. Oncol.202015101657166910.1016/j.jtho.2020.06.015 32599071
    [Google Scholar]
  35. TopalianS.L. HodiF.S. BrahmerJ.R. GettingerS.N. SmithD.C. McDermottD.F. PowderlyJ.D. CarvajalR.D. SosmanJ.A. AtkinsM.B. LemingP.D. SpigelD.R. AntoniaS.J. HornL. DrakeC.G. PardollD.M. ChenL. SharfmanW.H. AndersR.A. TaubeJ.M. McMillerT.L. XuH. KormanA.J. Jure-KunkelM. AgrawalS. McDonaldD. KolliaG.D. GuptaA. WiggintonJ.M. SznolM. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.N. Engl. J. Med.2012366262443245410.1056/NEJMoa1200690 22658127
    [Google Scholar]
  36. MorishimaT. MatsumotoY. KoedaN. ShimadaH. MaruhamaT. MatsukiD. NakataK. ItoY. TabuchiT. MiyashiroI. Impact of comorbidities on survival in gastric, colorectal, and lung cancer patients.J. Epidemiol.201929311011510.2188/jea.JE20170241 30012908
    [Google Scholar]
  37. ChuT. ZhongR. ZhongH. ZhangB. ZhangW. ShiC. QianJ. ZhangY. ChangQ. ZhangX. DongY. TengJ. GaoZ. QiangH. NieW. ZhaoY. HanY. ChenY. HanB. Phase 1b study of sintilimab plus anlotinib as first-line therapy in patients with advanced NSCLC.J. Thorac. Oncol.202116464365210.1016/j.jtho.2020.11.026 33524601
    [Google Scholar]
  38. Prospective clinical study of anlotinib hydrochloride capsule combined with penpulimab injection in the front-line treatment of advanced non-small cell lung cancer patients2024Available from:https://adisinsight.springer.com/trials/700372475
    [Google Scholar]
  39. DavisH.E. McCorkellL. VogelJ.M. TopolE.J. Long COVID: major findings, mechanisms and recommendations.Nat. Rev. Microbiol.2023213133146
    [Google Scholar]
/content/journals/ccdt/10.2174/0115680096364469250113105648
Loading
/content/journals/ccdt/10.2174/0115680096364469250113105648
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test