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2000
Volume 11, Issue 1
  • ISSN: 2212-697X
  • E-ISSN: 2212-6988

Abstract

Durvalumab, the programmed death-ligand 1 (PD-L1) targeting monoclonal antibody, has revolutionized the treatment of numerous cancers, such as Non-Small Cell Lung Cancer (NSCLC). Despite producing remarkable clinical advantages, immune-related toxicities, ., pneumonitis and colitis, are being closely monitored and must be treated on an individual basis. The safety profile, including immune-related toxicities, must be carefully considered. The role of Durvalumab as a consolidative treatment for unresectable stage III NSCLC, as demonstrated in the PACIFIC trial, marked a significant milestone in the adoption of immunotherapy. However, recent findings suggest that its benefit varies among patient subgroups, highlighting the need for more precise biomarkers beyond PD-L1 expression. Ongoing trials, such as PACIFIC-9 and AEGEAN, are investigating durvalumab in different settings and combination therapies with an aim to overcome resistance mechanisms. The PACIFIC-9 is an example where durvalumab is being combined with the CD73-blocking anti-CD73 antibody oleclumab and the CD94/NKG2A-blocking monalizumab in unresectable stage III NSCLC patients who maintain a stable response through chemoradiotherapy. Early findings are encouraging, but phase III efficacy data remain awaited. Heterogeneity in treatment response between tumor types, including bladder carcinoma, head and neck cancers, and cholangiocarcinoma, is one reason why it is worth aiming for tumor-intrinsic and microenvironmental determinants of responsiveness to immunotherapy. Durvalumab is of landmark significance in a range of malignancies but needs further efforts in the characterization of resistance mechanisms, the optimization of combination strategies, and the development of predictive models for the guidance of personalised therapeutic regimens.

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2025-06-11
2025-09-27

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References

  1. TanS. LiuK. ChaiY. Distinct PD-L1 binding characteristics of therapeutic monoclonal antibody durvalumab.Protein Cell20189113513910.1007/s13238‑017‑0412‑828488247
     [Google Scholar]
  2. ParvezA. ChoudharyF. MudgalP. PD-1 and PD-L1: architects of immune symphony and immunotherapy breakthroughs in cancer treatment.Front. Immunol.202314129634110.3389/fimmu.2023.129634138106415
     [Google Scholar]
  3. JavedS.A. NajmiA. AhsanW. ZoghebiK. Targeting PD-1/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges.Front. Immunol.202415138345610.3389/fimmu.2024.138345638660299
     [Google Scholar]
  4. MamdaniH. MatosevicS. KhalidA.B. DurmG. JalalS.I. Immunotherapy in lung cancer: current landscape and future directions.Front. Immunol.20221382361810.3389/fimmu.2022.82361835222404
     [Google Scholar]
  5. SpigelD.R. Faivre-FinnC. GrayJ.E. Five-year survival outcomes from the PACIFIC trial: durvalumab after chemoradiotherapy in stage III non–small-cell lung cancer.J. Clin. Oncol.202240121301131110.1200/JCO.21.0130835108059
     [Google Scholar]
  6. MarkhamM.J. WachterK. AgarwalN. Clinical cancer advances 2020: annual report on progress against cancer from the American Society of Clinical Oncology.J. Clin. Oncol.20203810108110.1200/JCO.19.0314132013670
     [Google Scholar]
  7. KelleyR.K. SangroB. HarrisW. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study.J. Clin. Oncol.202139272991300110.1200/JCO.20.0355534292792
     [Google Scholar]
  8. LeiC. KongX. LiY. PD-1/PD-L1 inhibitor-related adverse events and their management in breast cancer.J. Cancer20241592770278710.7150/jca.8543338577606
     [Google Scholar]
  9. BoussiosS. SheriffM. RassyE. Immuno-oncology: a narrative review of gastrointestinal and hepatic toxicities.Ann. Transl. Med.20219542310.21037/atm‑20‑736133842644
     [Google Scholar]
  10. SuP.L. FuruyaN. AsrarA. Recent advances in therapeutic strategies for non-small cell lung cancer.J. Hematol. Oncol.20251813510.1186/s13045‑025‑01679‑140140911
     [Google Scholar]
  11. HeymachJ.V. HarpoleD. MitsudomiT. Perioperative durvalumab for resectable non–small-cell lung cancer.N. Engl. J. Med.2023389181672168410.1056/NEJMoa230487537870974
     [Google Scholar]
  12. HeymachJ.V. MitsudomiT. HarpoleD. Design and rationale for a phase III, double-blind, placebo-controlled study of neoadjuvant durvalumab+ chemotherapy followed by adjuvant durvalumab for the treatment of patients with resectable stages II and III non-small-cell lung cancer: the AEGEAN trial.Clin. Lung Cancer2022233e247e25110.1016/j.cllc.2021.09.01034819266
     [Google Scholar]
  13. LauriolaA. DavalliP. MarvertiG. SantiS. CaporaliA. D’ArcaD. Targeting the interplay of independent cellular pathways and immunity: a challenge in cancer immunotherapy.Cancers20231511300910.3390/cancers1511300937296972
     [Google Scholar]
  14. ChickR.C. GundersonA.J. RahmanS. CloydJ.M. Neoadjuvant immunotherapy for localized pancreatic cancer: challenges and early results.Cancers20231515396710.3390/cancers1515396737568782
     [Google Scholar]
  15. MegyesfalviZ. GayC.M. PopperH. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions.CA Cancer J. Clin.202373662065210.3322/caac.2178537329269
     [Google Scholar]
  16. GuY. BenaventeC.A. Landscape and treatment options of shapeshifting small cell lung cancer.J. Clin. Med.20241311312010.3390/jcm1311312038892831
     [Google Scholar]
  17. SpigelD.R. ChengY. ChoB.C. LaktionovK.K. FangJ. ChenY. ADRIATIC: Durvalumab (D) as consolidation treatment (tx) for patients (pts) with limited-stage small-cell lung cancer (LS-SCLC).J. Clin. Oncol.20244217_supplLBA5LBA510.1200/JCO.2024.42.17_suppl.LBA5
     [Google Scholar]
  18. PanB. ShenB. The ADRIATIC study: revolutionizing the standard treatment paradigm for concurrent chemoradiotherapy in limited-stage small cell lung cancer.Journal of the National Cancer Center2025511210.1016/j.jncc.2024.12.00340040876
     [Google Scholar]
  19. ChenY. LiH. FanY. Shaping the tumor immune microenvironment of SCLC: Mechanisms, and opportunities for immunotherapy.Cancer Treat. Rev.202312010260610.1016/j.ctrv.2023.10260637579532
     [Google Scholar]
  20. LuS. SteinJ.E. RimmD.L. Comparison of biomarker modalities for predicting response to PD-1/PD-L1 checkpoint blockade: a systematic review and meta-analysis.JAMA Oncol.2019581195120410.1001/jamaoncol.2019.154931318407
     [Google Scholar]
  21. MellL.K. Torres-SaavedraP.A. WongS.J. Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial.Lancet Oncol.202425121576158810.1016/S1470‑2045(24)00507‑239551064
     [Google Scholar]
  22. TabernaM. OlivaM. MesíaR. Cetuximab-containing combinations in locally advanced and recurrent or metastatic head and neck squamous cell carcinoma.Front. Oncol.2019938310.3389/fonc.2019.0038331165040
     [Google Scholar]
  23. Marin-AcevedoJ.A. WithycombeB.M. KimY. Cetuximab for immunotherapy-refractory/ineligible cutaneous squamous cell carcinoma.Cancers20231512318010.3390/cancers1512318037370790
     [Google Scholar]
  24. BarlesiF. ChoB.C. GoldbergS.B. PACIFIC-9: Phase III trial of durvalumab + oleclumab or monalizumab in unresectable stage III non-small-cell lung cancer.Future Oncol.202420292137214710.1080/14796694.2024.235416039023287
     [Google Scholar]
  25. BarlesiF. GoldbergS.B. MannH. GopinathanA. NewtonM.D. AggarwalC. Phase 3 study of durvalumab combined with oleclumab or monalizumab in patients with unresectable stage III NSCLC (PACIFIC-9).J. Clin. Oncol.20234116Suppl.TPS8610TPS0
     [Google Scholar]
  26. BorgeaudM. SandovalJ. ObeidM. Novel targets for immune-checkpoint inhibition in cancer.Cancer Treat. Rev.202312010261410.1016/j.ctrv.2023.10261437603905
     [Google Scholar]
  27. FungS. SyedY.Y. Durvalumab: a review in advanced biliary tract cancer.Target. Oncol.202318696597210.1007/s11523‑023‑01007‑y37943483
     [Google Scholar]
  28. AntoniaS.J. VillegasA. DanielD. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC.N. Engl. J. Med.2018379242342235010.1056/NEJMoa180969730280658
     [Google Scholar]
  29. MeciA. GoyalN. SlonimskyG. Mechanisms of resistance and therapeutic perspectives in immunotherapy for advanced head and neck cancers.Cancers202416470310.3390/cancers1604070338398094
     [Google Scholar]
  30. Birnboim-PerachR. BenharI. Using combination therapy to overcome diverse challenges of immune checkpoint inhibitors treatment.Int. J. Biol. Sci.202420103911392210.7150/ijbs.9369739113705
     [Google Scholar]
  31. SantarpiaM. AguilarA. ChaibI. Non-small-cell lung cancer signaling pathways, metabolism, and PD-1/PD-L1 antibodies.Cancers2020126147510.3390/cancers1206147532516941
     [Google Scholar]
  32. GargP. PareekS. KulkarniP. HorneD. SalgiaR. SinghalS.S. Next-generation immunotherapy: advancing clinical applications in cancer treatment.J. Clin. Med.20241321653710.3390/jcm1321653739518676
     [Google Scholar]
/content/journals/ccand/10.2174/012212697X382513250603090514
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  • Article Type:     Editorial
Keyword(s): chemotherapy; clinical trials; Durvalumab; immunotherapy; non-small cell lung cancer (NSCLC); tumor microenvironment

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