The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab
in Solid Tumors

Mengmeng      Chen; Jian      Jiang; Junyu      Chen; Mengqi      Wang; Yaci      Lu; Lei      Liu; Lijing      Zhao; Lisheng      Wang
doi:10.2174/1389450124666230330101651
Abstract

Programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) checkpoint inhibitors have been on the front line of clinical revolution in which, the targeted PD-L1 therapy has obtained some success in patients with solid tumors. A large number of clinical trials revealed that both monotherapy and combination therapy of PD-L1 antibody significantly suppress some tumor growth and promote the survival of patients. At present, anti-PD-L1 treatment has been used as a portion of standard treatment for lung cancer, breast cancer, head and neck squamous cell carcinoma, and urothelial carcinoma. Although much evidence has demonstrated that PD-L1 antibody is safe in most patients, there are still some adverse reactions, such as pneumonitis, hepatitis, colitis, neurologic events and myocarditis. In this review, the clinical information, including the efficacy and safety of durvalumab in solid tumors, was enumerated and summarized at this stage to grasp the current application of targeted PD-L1 therapy and provide guidance for clinical application.
« Previous Next »
Graphical Abstract

[1]
Citrin DE. Recent Developments in Radiotherapy. N Engl J Med  2017; 377(11): 1065-75.
 [http://dx.doi.org/10.1056/NEJMra1608986] [PMID: 28902591]

[2]
Ahmad SS, Duke S, Jena R, Williams MV, Burnet NG. Advances in radiotherapy. BMJ  2012; 345(dec04 1): e7765.
 [http://dx.doi.org/10.1136/bmj.e7765] [PMID: 23212681]

[3]
Rivera Vargas T, Apetoh L. Danger signals: Chemotherapy enhancers?. Immunol Rev  2017; 280(1): 175-93.
 [http://dx.doi.org/10.1111/imr.12581] [PMID: 29027217]

[4]
O’Donnell JS, Teng MWL, Smyth MJ. Cancer immunoediting and resistance to T cell-based immunotherapy. Nat Rev Clin Oncol  2019; 16(3): 151-67.
 [http://dx.doi.org/10.1038/s41571-018-0142-8] [PMID: 30523282]

[5]
Walk EE, Yohe SL, Beckman A, et al. The Cancer Immunotherapy Biomarker Testing Landscape. Arch Pathol Lab Med  2020; 144(6): 706-24.
 [http://dx.doi.org/10.5858/arpa.2018-0584-CP] [PMID: 31714809]

[6]
Sanmamed MF, Chen L. A Paradigm Shift in Cancer Immunotherapy: From Enhancement to Normalization. Cell  2018; 175(2): 313-26.
 [http://dx.doi.org/10.1016/j.cell.2018.09.035] [PMID: 30290139]

[7]
Yi M, Jiao D, Xu H, et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer  2018; 17(1): 129.
 [http://dx.doi.org/10.1186/s12943-018-0864-3] [PMID: 30139382]

[8]
Akinleye A, Rasool Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J Hematol Oncol  2019; 12(1): 92.
 [http://dx.doi.org/10.1186/s13045-019-0779-5] [PMID: 31488176]

[9]
Syed YY. Durvalumab: First Global Approval. Drugs  2017; 77(12): 1369-76.
 [http://dx.doi.org/10.1007/s40265-017-0782-5] [PMID: 28643244]

[10]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Jemal A. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries: Global cancer statistics 2018. CA A Cancer Journal for Clinicians  2018; 68(suppl 8)

[11]
Walters S, Maringe C, Coleman MP, et al. Lung cancer survival and stage at diagnosis in Australia, Canada, Denmark, Norway, Sweden and the UK: A population-based study, 2004–2007. Thorax  2013; 68(6): 551-64.
 [http://dx.doi.org/10.1136/thoraxjnl-2012-202297] [PMID: 23399908]

[12]
Garassino MC, Cho BC, Kim JH, et al. Durvalumab as third-line or later treatment for advanced non-small-cell lung cancer (ATLANTIC): An open-label, single-arm, phase 2 study. Lancet Oncol  2018; 19(4): 521-36.
 [http://dx.doi.org/10.1016/S1470-2045(18)30144-X] [PMID: 29545095]

[13]
Mark M, Froesch P, Eboulet EI, et al. SAKK 19/17: Safety analysis of first-line durvalumab in patients with PD-L1 positive, advanced nonsmall cell lung cancer and a performance status of 2. Cancer Immunol Immunother  2021; 70(5): 1255-62.
 [http://dx.doi.org/10.1007/s00262-020-02757-8] [PMID: 33130956]

[14]
Gray JE, Villegas A, Daniel D, et al. Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC—update from PACIFIC. J Thorac Oncol  2020; 15(2): 288-93.
 [http://dx.doi.org/10.1016/j.jtho.2019.10.002] [PMID: 31622733]

[15]
Antonia SJ, Villegas A, Daniel D, et al. Overall survival with durvalumab after chemoradiotherapy in stage III NSCLC. N Engl J Med  2018; 379(24): 2342-50.
 [http://dx.doi.org/10.1056/NEJMoa1809697] [PMID: 30280658]

[16]
Antonia S, Goldberg SB, Balmanoukian A, et al. Safety and antitumour activity of durvalumab plus tremelimumab in non-small cell lung cancer: A multicentre, phase 1b study. Lancet Oncol  2016; 17(3): 299-308.
 [http://dx.doi.org/10.1016/S1470-2045(15)00544-6] [PMID: 26858122]

[17]
Bang YJ, Golan T, Dahan L, et al. Ramucirumab and durvalumab for previously treated, advanced non–small-cell lung cancer, gastric/gastro-oesophageal junction adenocarcinoma, or hepatocellular carcinoma: An open-label, phase Ia/b study (JVDJ). Eur J Cancer  2020; 137: 272-84.
 [http://dx.doi.org/10.1016/j.ejca.2020.06.007] [PMID: 32827847]

[18]
Planchard D, Reinmuth N, Orlov S, et al. ARCTIC: durvalumab with or without tremelimumab as third-line or later treatment of metastatic non-small-cell lung cancer. Ann Oncol  2020; 31(5): 609-18.
 [http://dx.doi.org/10.1016/j.annonc.2020.02.006] [PMID: 32201234]

[19]
Juergens RA, Hao D, Ellis PM, et al. A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226. Lung Cancer  2020; 143: 1-11.
 [http://dx.doi.org/10.1016/j.lungcan.2020.02.016] [PMID: 32169783]

[20]
Rizvi NA, Cho BC, Reinmuth N, et al. Durvalumab with or without tremelimumab vs standard chemotherapy in first-line treatment of metastatic non–small cell lung cancer. JAMA Oncol  2020; 6(5): 661-74.
 [http://dx.doi.org/10.1001/jamaoncol.2020.0237] [PMID: 32271377]

[21]
Creelan BC, Yeh TC, Kim SW, et al. A Phase 1 study of gefitinib combined with durvalumab in EGFR TKI-naive patients with EGFR mutation-positive locally advanced/metastatic non-small-cell lung cancer. Br J Cancer  2021; 124(2): 383-90.
 [http://dx.doi.org/10.1038/s41416-020-01099-7] [PMID: 33012782]

[22]
Oxnard GR, Yang JCH, Yu H, et al. TATTON: A multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer. Ann Oncol  2020; 31(4): 507-16.
 [http://dx.doi.org/10.1016/j.annonc.2020.01.013] [PMID: 32139298]

[23]
Oronsky B, Reid TR, Oronsky A, Carter CA. What’s new in SCLC? A review. Neoplasia  2017; 19(10): 842-7.
 [http://dx.doi.org/10.1016/j.neo.2017.07.007] [PMID: 28888101]

[24]
Goldman JW, Dowlati A, Antonia SJ, et al. Safety and antitumor activity of durvalumab monotherapy in patients with pretreated extensive disease small-cell lung cancer (ED-SCLC). J Clin Oncol  2018; 36(15_suppl) (Suppl.): 8518-8.
 [http://dx.doi.org/10.1200/JCO.2018.36.15_suppl.8518]

[25]
Goldman JW, Dvorkin M, Chen Y, et al. Durvalumab, with or without tremelimumab, plus platinum–etoposide versus platinum–etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): Updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol  2021; 22(1): 51-65.
 [http://dx.doi.org/10.1016/S1470-2045(20)30539-8] [PMID: 33285097]

[26]
Pakkala S, Higgins K, Chen Z, et al. Durvalumab and tremelimumab with or without stereotactic body radiation therapy in relapsed small cell lung cancer: A randomized phase II study. J Immunother Cancer  2020; 8(2): e001302.
 [http://dx.doi.org/10.1136/jitc-2020-001302] [PMID: 33428583]

[27]
Bondarenko I, Juan-Vidal O, Pajkos G, et al. 1665PDPreliminary efficacy of durvalumab plus tremelimumab in platinum-refractory/resistant ED-SCLC from arm A of the phase II BALTIC study. Annals of Oncology  2018; 29(8)

[28]
Thomas A, Vilimas R, Trindade C, et al. Durvalumab in combination with olaparib in patients with relapsed SCLC: Results from a phase II study. J Thorac Oncol  2019; 14(8): 1447-57.
 [http://dx.doi.org/10.1016/j.jtho.2019.04.026] [PMID: 31063862]

[29]
Iams WT, Porter J, Horn L. Immunotherapeutic approaches for small-cell lung cancer. Nat Rev Clin Oncol  2020; 17(5): 300-12.
 [http://dx.doi.org/10.1038/s41571-019-0316-z] [PMID: 32055013]

[30]
Smyth EC, Nilsson M, Grabsch HI, van Grieken NCT, Lordick F. Gastric cancer. Lancet  2020; 396(10251): 635-48.
 [http://dx.doi.org/10.1016/S0140-6736(20)31288-5] [PMID: 32861308]

[31]
Kelly RJ, Lee J, Bang YJ, et al. Safety and efficacy of durvalumab and tremelimumab alone or in combination in patients with advanced gastric and gastroesophageal junction adenocarcinoma. Clin Cancer Res  2020; 26(4): 846-54.
 [http://dx.doi.org/10.1158/1078-0432.CCR-19-2443] [PMID: 31676670]

[32]
Bang YJ, Kaufman B, Geva R, et al. An open-label, phase II basket study of olaparib and durvalumab (MEDIOLA): Results in patients with relapsed gastric cancer. J Clin Oncol  2019; 37(4_suppl) (Suppl.): 140-0.
 [http://dx.doi.org/10.1200/JCO.2019.37.4_suppl.140]

[33]
Kelley RK, Sangro B, Harris W, et al. 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  2021; 39(27): 2991-3001.
 [http://dx.doi.org/10.1200/JCO.20.03555] [PMID: 34292792]

[34]
Iyer RV, Li D, Dayyani F, Phan AT, Needle MN, Abrams TA. DEDUCTIVE: A study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma—Phase Ib results. J Clin Oncol  2021; 39(3_suppl) (Suppl.): 294-4.
 [http://dx.doi.org/10.1200/JCO.2021.39.3_suppl.294] [PMID: 34890242]

[35]
Chen EX, Jonker DJ, Loree JM, et al. Effect of combined immune checkpoint inhibition vs Best Supportive Care Alone in patients with advanced colorectal cancer. JAMA Oncol  2020; 6(6): 831-8.
 [http://dx.doi.org/10.1001/jamaoncol.2020.0910] [PMID: 32379280]

[36]
Levy A, Massard C, Soria JC, Deutsch E. Concurrent irradiation with the anti-programmed cell death ligand-1 immune checkpoint blocker durvalumab: Single centre subset analysis from a phase 1/2 trial. Eur J Cancer  2016; 68: 156-62.
 [http://dx.doi.org/10.1016/j.ejca.2016.09.013] [PMID: 27764686]

[37]
Taylor K, Loo Yau H, Chakravarthy A, et al. An open-label, phase II multicohort study of an oral hypomethylating agent CC-486 and durvalumab in advanced solid tumors. J Immunother Cancer  2020; 8(2): e000883.
 [http://dx.doi.org/10.1136/jitc-2020-000883] [PMID: 32753546]

[38]
Cassier PA, Garin G, Eberst L, et al. MEDIPLEX: A phase 1 study of durvalumab (D) combined with pexidartinib (P) in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). J Clin Oncol  2019; 37(15_suppl) (Suppl.): 2579-9.
 [http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.2579]

[39]
Hong D, Rasco D, Veeder M, et al. A Phase 1b/2 Study of the Bruton Tyrosine Kinase Inhibitor Ibrutinib and the PD-L1 Inhibitor Durvalumab in Patients with Pretreated Solid Tumors. Oncology  2019; 97(2): 102-11.
 [http://dx.doi.org/10.1159/000500571] [PMID: 31230047]

[40]
Xie C, Duffy AG, Brar G, et al. Immune checkpoint blockade in combination with stereotactic body radiotherapy in patients with metastatic pancreatic ductal adenocarcinoma. Clin Cancer Res  2020; 26(10): 2318-26.
 [http://dx.doi.org/10.1158/1078-0432.CCR-19-3624]

[41]
Gou M, Zhang Y, Si H, Dai G. Efficacy and safety of nivolumab for metastatic biliary tract cancer. OncoTargets Ther  2019; 12: 861-7.
 [http://dx.doi.org/10.2147/OTT.S195537] [PMID: 30774373]

[42]
Bang YJ, Ueno M, Malka D, et al. Pembrolizumab (pembro) for advanced biliary adenocarcinoma: Results from the KEYNOTE-028 (KN028) and KEYNOTE-158 (KN158) basket studies. J Clin Oncol  2019; 37(15_suppl) (Suppl.): 4079-9.
 [http://dx.doi.org/10.1200/JCO.2019.37.15_suppl.4079]

[43]
Boilève A, Hilmi M, Gougis P, et al. Triplet combination of durvalumab, tremelimumab, and paclitaxel in biliary tract carcinomas: Safety run-in results of the randomized IMMUNOBIL PRODIGE 57 phase II trial. Eur J Cancer  2021; 143: 55-63.
 [http://dx.doi.org/10.1016/j.ejca.2020.10.027] [PMID: 33279854]

[44]
Ioka T, Ueno M, Oh DY, et al. Evaluation of safety and tolerability of durvalumab (D) with or without tremelimumab (T) in patients (pts) with biliary tract cancer (BTC). J Clin Oncol  2019; 37(4_suppl) (Suppl.): 387-7.
 [http://dx.doi.org/10.1200/JCO.2019.37.4_suppl.387]

[45]
Shah RB, Montgomery JS, Montie JE, Kunju LP. Variant (divergent) histologic differentiation in urothelial carcinoma is under-recognized in community practice: Impact of mandatory central pathology review at a large referral hospital. Urol Oncol  2013; 31(8): 1650-5.
 [http://dx.doi.org/10.1016/j.urolonc.2012.04.009] [PMID: 22608543]

[46]
Powles T, O’Donnell PH, Massard C, et al. Efficacy and Safety of Durvalumab in Locally Advanced or Metastatic Urothelial Carcinoma. JAMA Oncol  2017; 3(9): e172411.
 [http://dx.doi.org/10.1001/jamaoncol.2017.2411] [PMID: 28817753]

[47]
Ptp A, Msvdh B, Dc C, et al. Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol  2020; 21(12): 1574-88.

[48]
Gao J, Navai N, Alhalabi O, et al. Neoadjuvant PD-L1 plus CTLA-4 blockade in patients with cisplatin-ineligible operable high-risk urothelial carcinoma. Nat Med  2020; 26(12): 1845-51.
 [http://dx.doi.org/10.1038/s41591-020-1086-y] [PMID: 33046869]

[49]
Marandino L, Raggi D, Calareso G, et al. Cabozantinib Plus Durvalumab in Patients With Advanced Urothelial Carcinoma After Platinum Chemotherapy: Safety and Preliminary Activity of the Open-Label, Single-Arm, Phase 2 ARCADIA Trial. Clin Genitourin Cancer  2021; 19(5): 457-65.
 [http://dx.doi.org/10.1016/j.clgc.2021.04.001] [PMID: 34006499]

[50]
Joshi M, Zakharia Y, Kaag M, et al. Concurrent Durvalumab And Radiation Therapy (DUART) followed by Adjuvant Durvalumab in Patients with Localized Urothelial Cancer of Bladder: BTCRC-GU15-023. Int J Radiat Oncol Biol Phys  2020; 108(3): S29-30.
 [http://dx.doi.org/10.1016/j.ijrobp.2020.07.2124]

[51]
Claps M, Mennitto A, Guadalupi V, et al. Immune-checkpoint inhibitors and metastatic prostate cancer therapy: Learning by making mistakes. Cancer Treat Rev  2020; 88: 102057.
 [http://dx.doi.org/10.1016/j.ctrv.2020.102057] [PMID: 32574991]

[52]
Karzai F, Madan RA, Owens H, et al. Combination of PDL-1 and PARP inhibition in an unselected population with metastatic castrate-resistant prostate cancer (mCRPC). J Clin Oncol  2017; 35(15_suppl) (Suppl.): 5026-6.
 [http://dx.doi.org/10.1200/JCO.2017.35.15_suppl.5026]

[53]
Karzai F, VanderWeele D, Madan RA, et al. Activity of durvalumab plus olaparib in metastatic castration-resistant prostate cancer in men with and without DNA damage repair mutations. J Immunother Cancer  2018; 6(1): 141.
 [http://dx.doi.org/10.1186/s40425-018-0463-2] [PMID: 30514390]

[54]
Krebs MG, Lopez J, El-Khoueiry A, et al. Abstract CT026: Phase I study of AZD6738, an inhibitor of ataxia telangiectasia Rad3-related (ATR), in combination with olaparib or durvalumab in patients (pts) with advanced solid cancers. Cancer Res  2018; 78(13_Supplement) (Suppl.): CT026-6.
 [http://dx.doi.org/10.1158/1538-7445.AM2018-CT026]

[55]
Naing A, Powderly JD, Falchook G, et al. Abstract CT177: Epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study. Cancer Res  2018; 78(13_Supplement) (Suppl.): CT177-7.
 [http://dx.doi.org/10.1158/1538-7445.AM2018-CT177]

[56]
Foguer K, Braga MS, Peron JPS, et al. Endostatin gene therapy inhibits intratumoral macrophage M2 polarizatio. Biomed Pharmacother  2016; 79: 102-1.

[57]
Callahan MK, Odunsi K, Sznol M, Nemunaitis J, Wolchok JD. Abstract A006: Phase 1 study to evaluate the safety and tolerability of MEDI4736 (durvalumab, durva) + tremelimumab (treme) in patients with advanced solid tumors. Cancer Immunol Res  2019; 7(2)

[58]
Zakharia Y, Singer EA, Ross R, et al. Phase Ib/II study of durvalumab and guadecitabine in advanced kidney cancer Big Ten Cancer Research Consortium BTCRC GU16-043. J Clin Oncol  2021; 39(6_suppl) (Suppl.): 328-8.
 [http://dx.doi.org/10.1200/JCO.2021.39.6_suppl.328]

[59]
Wu Y, Mou H. Complete remission in a patient with advanced renal pelvis carcinoma with lung metastasis treated with durvalumab immunotherapy: A case report. Ann Palliat Med  2020; 9(4): 2408-13.
 [http://dx.doi.org/10.21037/apm-20-1338] [PMID: 32762233]

[60]
Ditto A, Bogani G, Leone Roberti Maggiore U, et al. Oncologic effectiveness of nerve-sparing radical hysterectomy in cervical cancer. J Gynecol Oncol  2018; 29(3): e41.
 [http://dx.doi.org/10.3802/jgo.2018.29.e41] [PMID: 29533024]

[61]
Banerjee S, Oaknin A, Sanchez-Simon I, Salgado AC, Diamond JR. 518 Phase 1B trial of monalizumab (NKG2A inhibitor) plus durvalumab: Safety and efficacy in patients with metastatic ovarian, cervical, and microsatellite-stable endometrial cancers. Int J Gynecol Cancer  2020; 21(4): 90-117.

[62]
Slomovitz B, Bradley WH, Ghamande S, et al. Phase II study of durvalumab alone or in combination with ADXS11-001 (AXAL) in recurrent/persistent or metastatic cervical cancer. Gynecol Oncol  2020; 159: 4-5.
 [http://dx.doi.org/10.1016/j.ygyno.2020.06.008]

[63]
Grywalska E, Sobstyl M, Putowski L, Roliński J. Current Possibilities of Gynecologic Cancer Treatment with the Use of Immune Checkpoint Inhibitors. Int J Mol Sci  2019; 20(19): 4705.
 [http://dx.doi.org/10.3390/ijms20194705] [PMID: 31547532]

[64]
Antill YC, Kok PS, Robledo KP, Barnes E, Mileshkin LR. Activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601). J Clin Oncol  2019; 37(15): 5501-1.

[65]
Zimmer AS, Nichols E, Cimino-Mathews A, et al. A phase I study of the PD-L1 inhibitor, durvalumab, in combination with a PARP inhibitor, olaparib, and a VEGFR1–3 inhibitor, cediranib, in recurrent women’s cancers with biomarker analyses. J Immunother Cancer  2019; 7(1): 197.
 [http://dx.doi.org/10.1186/s40425-019-0680-3] [PMID: 31345267]

[66]
Lee JY, Kim S, Kim YT, et al. Changes in ovarian cancer survival during the 20 years before the era of targeted therapy. BMC Cancer  2018; 18(1): 601.
 [http://dx.doi.org/10.1186/s12885-018-4498-z] [PMID: 29843633]

[67]
Lampert EJ, Zimmer A, Padget M, et al. Combination of PARP Inhibitor Olaparib, and PD-L1 Inhibitor Durvalumab, in Recurrent Ovarian Cancer: A Proof-of-Concept Phase II Study. Clin Cancer Res  2020; 26(16): 4268-79.
 [http://dx.doi.org/10.1158/1078-0432.CCR-20-0056] [PMID: 32398324]

[68]
Zamarin D, Walderich S, Holland A, et al. Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: A phase II trial. J Immunother Cancer  2020; 8(1): e000829.
 [http://dx.doi.org/10.1136/jitc-2020-000829] [PMID: 32503949]

[69]
Falchook GS, Peeters M, Rottey S, et al. A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Invest New Drugs  2021; 39(5): 1284-97.
 [http://dx.doi.org/10.1007/s10637-021-01088-4] [PMID: 33852104]

[70]
Waks AG, Winer EP. Breast Cancer Treatment. JAMA  2019; 321(3): 316.
 [http://dx.doi.org/10.1001/jama.2018.20751] [PMID: 30667503]

[71]
Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med  2021; 27(2): 250-5.
 [http://dx.doi.org/10.1038/s41591-020-01189-2] [PMID: 33462450]

[72]
Loibl S, Untch M, Burchardi N, et al. A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. Ann Oncol  2019; 30(8): 1279-88.
 [http://dx.doi.org/10.1093/annonc/mdz158] [PMID: 31095287]

[73]
Ghebeh H, Al-Sayed A, Eiada R, et al. Weekly Paclitaxel given concurrently with Durvalumab has a favorable safety profile in triple-negative metastatic breast cancer. Sci Rep  2021; 11(1): 19154.
 [http://dx.doi.org/10.1038/s41598-021-98113-6] [PMID: 34580336]

[74]
Ahmed FS, Gaule P, McGuire J, et al. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clin Cancer Res  2020; 26(20): 5456-61.
 [http://dx.doi.org/10.1158/1078-0432.CCR-20-1303] [PMID: 32709714]

[75]
Pusztai L, Yau C, Wolf DM, et al. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell  2021; 39(7): 989-998.e5.
 [http://dx.doi.org/10.1016/j.ccell.2021.05.009] [PMID: 34143979]

[76]
Quintela-Fandino M, Holgado E, Manso L, et al. Immuno-priming durvalumab with bevacizumab in HER2-negative advanced breast cancer: A pilot clinical trial. Breast Cancer Res  2020; 22(1): 124.
 [http://dx.doi.org/10.1186/s13058-020-01362-y] [PMID: 33176887]

[77]
Domchek SM, Postel-Vinay S, Im SA, et al. Olaparib and durval-umab in patients with germline BRCA-mutated metastatic breast cancer (MEDIOLA): An open-label, multicentre, phase 1/2, basket study. Lancet Oncol  2020; 21(9): 1155-64.
 [http://dx.doi.org/10.1016/S1470-2045(20)30324-7] [PMID: 32771088]

[78]
Chia S, Bedard PL, Hilton J, et al. A Phase Ib Trial of Durvalumab in Combination with Trastuzumab in HER2-Positive Metastatic Breast Cancer (CCTG IND.229). Oncologist  2019; 24(11): 1439-45.
 [http://dx.doi.org/10.1634/theoncologist.2019-0321] [PMID: 31420468]

[79]
Leoncini E, Vukovic V, Cadoni G, et al. Clinical features and prognostic factors in patients with head and neck cancer: Results from a multicentric study. Cancer Epidemiol  2015; 39(3): 367-74.
 [http://dx.doi.org/10.1016/j.canep.2015.02.004] [PMID: 25770642]

[80]
Ferris RL, Haddad R, Even C, et al. Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study. Ann Oncol  2020; 31(7): 942-50.
 [http://dx.doi.org/10.1016/j.annonc.2020.04.001] [PMID: 32294530]

[81]
Siu LL, Even C, Mesía R, et al. Safety and Efficacy of Durvalumab with or Without Tremelimumab in Patients with PD-L1-Low/Negative Recurrent or Metastatic HNSCC: The Phase 2 CONDOR Randomized Clinical Trial. JAMA Oncol  2019; 5(2): 195-203.
 [PMID: 30383184]

[82]
Zandberg DP, Algazi AP, Jimeno A, et al. Durvalumab for recurrent or metastatic head and neck squamous cell carcinoma: Results from a single-arm, phase II study in patients with ≥25% tumour cell PD-L1 expression who have progressed on platinum-based chemotherapy. Eur J Cancer  2019; 107: 142-52.
 [http://dx.doi.org/10.1016/j.ejca.2018.11.015] [PMID: 30576970]

[83]
Segal NH, Ou SHI, Balmanoukian A, et al. Safety and efficacy of durvalumab in patients with head and neck squamous cell carcinoma: results from a phase I/II expansion cohort. Eur J Cancer  2019; 109: 154-61.
 [http://dx.doi.org/10.1016/j.ejca.2018.12.029] [PMID: 30731276]

[84]
Näsman A, Romanitan M, Nordfors C, et al. Tumor infiltrating CD8+ and Foxp3+ lymphocytes correlate to clinical outcome and human papillomavirus (HPV) status in tonsillar cancer. PLoS One  2012; 7(6): e38711.
 [http://dx.doi.org/10.1371/journal.pone.0038711] [PMID: 22701698]

[85]
Solomon B, Young RJ, Bressel M, et al. Prognostic Significance of PD-L1+ and CD8+ Immune Cells in HPV+ Oropharyngeal Squamous Cell Carcinoma. Cancer Immunol Res  2018; 6(3): 295-304.
 [http://dx.doi.org/10.1158/2326-6066.CIR-17-0299] [PMID: 29378694]

[86]
De Meulenaere A, Vermassen T, Aspeslagh S, et al. Tumor PD-L1 status and CD8+ tumor-infiltrating T cells: markers of improved prognosis in oropharyngeal cancer. Oncotarget  2017; 8(46): 80443-52.
 [http://dx.doi.org/10.18632/oncotarget.19045] [PMID: 29113315]

[87]
Ferrarotto R, Bell D, Rubin ML, et al. Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results. Clin Cancer Res  2020; 26(13): 3211-9.
 [http://dx.doi.org/10.1158/1078-0432.CCR-19-3977] [PMID: 32269052]

[88]
Moore AJ, Parker RJ, Wiggins J. Malignant mesothelioma. Orphanet J Rare Dis  2008; 3(1): 34.
 [http://dx.doi.org/10.1186/1750-1172-3-34] [PMID: 19099560]

[89]
Nowak AK, Lesterhuis WJ, Kok PS, et al. Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): A multicentre, single-arm, phase 2 trial with a safety run-in. Lancet Oncol  2020; 21(9): 1213-23.
 [http://dx.doi.org/10.1016/S1470-2045(20)30462-9] [PMID: 32888453]

[90]
Calabrò L, Morra A, Giannarelli D, et al. Tremelimumab combined with durvalumab in patients with mesothelioma (NIBIT-MESO-1): An open-label, non-randomised, phase 2 study. Lancet Respir Med  2018; 6(6): 451-60.
 [http://dx.doi.org/10.1016/S2213-2600(18)30151-6] [PMID: 29773326]

[91]
Calabrò L, Rossi G, Morra A, et al. Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: A follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study. Lancet Respir Med  2021; 9(9): 969-76.
 [http://dx.doi.org/10.1016/S2213-2600(21)00043-6] [PMID: 33844995]

[92]
Ribas A, Algazi A, Ascierto PA, et al. PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma. Nature Commun  2020; 11(1): 6262.

[93]
Kim R, Kwon M, An M, et al. Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced/metastatic melanoma who have failed prior anti-PD1 therapy. Ann Oncol 2021.
 [http://dx.doi.org/10.1016/j.annonc.2021.10.009] [PMID: 34710570]

[94]
Daassi D, Mahoney KM, Freeman GJ. The importance of exosomal PDL1 in tumour immune evasion. Nat Rev Immunol  2020; 20(4): 209-15.
 [http://dx.doi.org/10.1038/s41577-019-0264-y] [PMID: 31965064]

[95]
Vanella V, Festino L, Strudel M, Simeone E, Grimaldi AM, Ascierto PA. PD-L1 inhibitors in the pipeline: Promise and progress. OncoImmunology  2018; 7(1): e1365209.
 [http://dx.doi.org/10.1080/2162402X.2017.1365209] [PMID: 29296516]

[96]
Karunarathne DS, Horne-Debets JM, Huang JX, et al. Programmed Death-1 Ligand 2-Mediated Regulation of the PD-L1 to PD-1 Axis Is Essential for Establishing CD4 + T Cell Immunity. Immunity  2016; 45(2): 333-45.
 [http://dx.doi.org/10.1016/j.immuni.2016.07.017] [PMID: 27533014]

[97]
Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity  2007; 27(1): 111-22.
 [http://dx.doi.org/10.1016/j.immuni.2007.05.016] [PMID: 17629517]

[98]
Johansson H, Andersson R, Bauden M, Hammes S, Holdenrieder S, Ansari D. Immune checkpoint therapy for pancreatic cancer. World J Gastroenterol  2016; 22(43): 9457-76.
 [http://dx.doi.org/10.3748/wjg.v22.i43.9457] [PMID: 27920468]

[99]
Carlisle JW, Steuer CE, Owonikoko TK, Saba NF. An update on the immune landscape in lung and head and neck cancers. CA Cancer J Clin  2020; 70(6): 505-17.
 [http://dx.doi.org/10.3322/caac.21630] [PMID: 32841388]
Rights & Permissions Print Cite
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1389450124666230330101651	Print ISSN 1389-4501
Publisher Name Bentham Science Publisher	Online ISSN 1873-5592
Current Drug Targets

The Clinical Safety and Efficacy of Targeted PD-L1 Therapy with Durvalumab in Solid Tumors

Abstract Play Pause

Graphical Abstract

Related Journals

Related Books

Abstract
