Clinical activity and safety of atezolizumab in patients with recurrent glioblastoma

Journal of Neuro-Oncology

Volumn 140, Issue 2, 2018, Pages 317-328

  Lukas, Rimas V ^a,b   Rodon, Jordi ^c   Becker, Kevin ^d   Wong, Eric T ^e   Shih, Kent ^f   Touat, Mehdi ^g   Fassò, Marcella ^h   Osborne, Stuart ⁱ   Molinero, Luciana ^h   O’Hear, Carol ^h   Grossman, William ^h   Baehring, Joachim ^d  

^a NORTHWESTERN UNIVERSITY   (United States)

^b UNIVERSITY OF CHICAGO   (United States)

^c VALL D'HEBRON INSTITUTE OF ONCOLOGY   (Spain)

^d YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e HARVARD MEDICAL SCHOOL   (United States)

^f SARAH CANNON RESEARCH INSTITUTE   (United States)

^g INSTITUT GUSTAVE ROUSSY   (France)

^h GENENTECH INC   (United States)

ⁱ F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Atezolizumab; Glioblastoma (GBM); Programmed death ligand 1 (PD L1); Tumor mutational burden (TMB)

Indexed keywords

ALANINE AMINOTRANSFERASE; ASPARTATE AMINOTRANSFERASE; ATEZOLIZUMAB; BEVACIZUMAB; ISOCITRATE DEHYDROGENASE 1; ANTINEOPLASTIC AGENT; DNA DIRECTED DNA POLYMERASE ALPHA; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE; LIPID; MONOCLONAL ANTIBODY; MUTALIPOCIN I; POLE PROTEIN, HUMAN; POLY ADP RIBOSE BINDING PROTEIN; TUMOR MARKER;

ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; ANTINEOPLASTIC ACTIVITY; APRAXIA; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASTHENIA; BACKACHE; BRAIN EDEMA; CANCER CHEMOTHERAPY; CANCER GROWTH; CANCER RECURRENCE; CD4+ T LYMPHOCYTE; CLINICAL ARTICLE; COHORT ANALYSIS; CONSTIPATION; DECREASED APPETITE; DEHYDRATION; DERMATITIS; DIARRHEA; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERANCE; DYSGEUSIA; FATIGUE; FEMALE; FLUSHING; FOLLOW UP; GLIOBLASTOMA; GLOSSODYNIA; HEADACHE; HUMAN; HUMAN CELL; HUMAN TISSUE; HYPERHIDROSIS; IDH1 GENE; MACULOPAPULAR RASH; MALAISE; MALE; MUSCLE WEAKNESS; MYALGIA; NAUSEA; NIGHT SWEAT; ONCOGENE; OVERALL SURVIVAL; PATIENT MONITORING; PATIENT SELECTION; POLE GENE; PURPURA; RHINORRHEA; ROSACEA; SIDE EFFECT; SINUS CONGESTION; TOXICITY; TREATMENT DURATION; TREATMENT RESPONSE; URTICARIA; VOMITING; XEROSTOMIA; BRAIN TUMOR; CLINICAL TRIAL; GENETICS; INTRAVENOUS DRUG ADMINISTRATION; METABOLISM; MIDDLE AGED; MORTALITY; PHASE 1 CLINICAL TRIAL; TREATMENT OUTCOME; TUMOR RECURRENCE;

ADMINISTRATION, INTRAVENOUS; ADULT; AGED; ANTIBODIES, MONOCLONAL; ANTINEOPLASTIC AGENTS; BEVACIZUMAB; BIOMARKERS, TUMOR; BRAIN NEOPLASMS; DNA POLYMERASE II; FEMALE; FOLLOW-UP STUDIES; GLIOBLASTOMA; HUMANS; ISOCITRATE DEHYDROGENASE; LIPIDS; MALE; MIDDLE AGED; NEOPLASM RECURRENCE, LOCAL; POLY-ADP-RIBOSE BINDING PROTEINS; TREATMENT OUTCOME;

EID: 85051232998     PISSN: 0167594X     EISSN: 15737373     Source Type: Journal    
DOI: 10.1007/s11060-018-2955-9     Document Type: Article

References (52)

1. Ostrom QT, Gittleman H, Xu J, Kromer C, Wolinsky Y, Kruchko C, Barnholtz-Sloan JS (2016) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 18:v1–v75. 10.1093/neuonc/now207
2. Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, Ludwin SK, Allgeier A, Fisher B, Belanger K et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466. 10.1016/S1470-2045(09)70025-7
3. Lukas RV, Mrugala MM (2017) Pivotal therapeutic trials for infiltrating gliomas and how they affect clinical practice. Neuro-Oncol Pract 4(4):209–216. 10.1093/nop/npw016
4. Stupp R, Taillibert S, Kanner A, Read W, Steinberg DM, Lhermitte B, Toms S, Idbaih A, Ahluwalia MS, Fink K et al (2017) Effect of tumor-treating fields plus maintenance temozolomide vs maintenance temozolomide alone on survival in patients with glioblastoma: a randomized clinical trial. JAMA 318:2306–2316. 10.1001/jama.2017.18718
5. Weller M, van den Bent M, Hopkins K, Tonn JC, Stupp R, Falini A, Cohen-Jonathan-Moyal E, Frappaz D, Henriksson R, Balana C et al (2014) EANO guideline for the diagnosis and treatment of anaplastic gliomas and glioblastoma. Lancet Oncol 15:e395–e403. 10.1016/S1470-2045(14)70011-7
6. Touat M, Ibdaih A, Sanson A, Ligon KL (2017) Glioblastoma targeted therapy: updated approaches from recent biological insights. Ann Oncol 28(7):1457–1462. 10.1093/annonc/mdx106
7. Wong ET, Gautam S, Malchow C, Lun M, Pan E, Brem S (2011) Bevacizumab for recurrent glioblastoma multiforme: a meta-analysis. J Natl Compr Canc Netw 9:403–407
8. Stupp R, Wong ET, Kanner AA, Steinberg D, Engelhard H, Heidecke V, Kirson ED, Taillibert S, Liebermann F, Dbaly V et al (2012) NovoTTF-100A versus physician’s choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality. Eur J Cancer 48:2192–2202. 10.1016/j.ejca.2012.04.011
9. Herbst RS, Soria JC, Kowanetz M, Fine GD, Hamid O, Gordon MS, Sosman JA, McDermott DF, Powderly JD, Gettinger SN et al (2014) Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature 515:563–567. 10.1038/nature14011
10. Chen DS, Irving BA, Hodi FS (2012) Molecular pathways: next-generation immunotherapy: inhibiting programmed death-ligand 1 and programmed death-1. Clin Cancer Res 18:6580–6587. 10.1158/1078-0432.CCR-12-1362
11. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515:558–562. 10.1038/nature13904
12. Matsumoto K, Fukuyama S, Eguchi-Tsuda M, Nakano T, Matsumoto T, Matsumura M, Moriwaki A, Kan-o K, Wada Y, Yagita H et al (2008) B7-DC induced by IL-13 works as a feedback regulator in the effector phase of allergic asthma. Biochem Biophys Res Commun 365:170–175. 10.1016/j.bbrc.2007.10.156
13. Akbari O, Stock P, Singh AK, Lombardi V, Lee WL, Freeman GJ, Sharpe AH, Umetsu DT, Dekruyff RH (2010) PD-L1 and PD-L2 modulate airway inflammation and iNKT-cell-dependent airway hyperreactivity in opposing directions. Mucosal Immunol 3:81–91. 10.1038/mi.2009.112
14. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O’Donnell PH, Balmanoukian A, Loriot Y et al (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet 387:1909–1920. 10.1016/S0140-6736(16)00561-4
15. Balar AV, Galsky MD, Rosenberg JE, Powles T, Petrylak DP, Bellmunt J, Loriot Y, Necchi A, Hoffman-Censits J, Perez-Gracia JL et al (2017) Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet 389:67–76
16. Rittmeyer A, Barlesi F, Waterkamp D, Park K, Ciardiello F, von Pawel J, Gadgeel SM, Hida T, Kowalski DM, Dols MC et al (2017) Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Lancet 389:255–265
17. Tecentriq (atezolizumab) (2018) [product insert]. Genentech, Inc., South San Francisco
18. Berghoff AS, Kiesel B, Widhalm G, Rajky O, Ricken G, Wohrer A, Dieckmann K, Filipits M, Brandstetter A, Weller M et al (2015) Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol 17:1064–1075. 10.1093/neuonc/nou307
19. Vlahovic G, Fecci PE, Reardon D, Sampson JH (2015) Programmed death ligand 1 (PD-L1) as an immunotherapy target in patients with glioblastoma. Neuro Oncol 17:1043–1045. 10.1093/neuonc/nov071
20. Binder DC, Davis AA, Wainwright DA (2015) Immunotherapy for cancer in the central nervous system: current and future directions. Oncoimmunology 5:e1082027. 10.1080/2162402X.2015.1082027
21. Balar AV, Weber JS (2017) PD-1 and PD-L1 antibodies in cancer: current status and future directions. Cancer Immunol Immunother 66:551–564. 10.1007/s00262-017-1954-6
22. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D et al (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520. 10.1056/NEJMoa1500596
23. McGranahan N, Furness AJ, Rosenthal R, Ramskov S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA, Birkbak NJ, Hiley CT et al (2016) Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 351:1463–1469. 10.1126/science.aaf1490
24. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128. 10.1126/science.aaa1348
25. Bouffet E, Larouche V, Campbell BB, Merico D, de Borja R, Aronson M, Durno C, Krueger J, Cabric V, Ramaswamy V et al (2016) Immune checkpoint inhibition for hypermutant glioblastoma multiforme resulting from germline biallelic mismatch repair deficiency. J Clin Oncol 34:2206–2211. 10.1200/JCO.2016.66.6552
26. Hodges TR, Ott M, Xiu J, Gatalica Z, Swensen J, Zhou S, Huse JT, de Groot J, Li S, Overwijk WW et al (2017) Mutational burden, immune checkpoint expression, and mismatch repair in glioma: implications for immune checkpoint immunotherapy. Neuro Oncol. 10.1093/neuonc/nox026
27. Omuro A, Vlahovic G, Lim M, Sahebjam S, Baehring J, Cloughesy T, Voloschin A, Ramkissoon SH, Ligon KL, Latek R et al (2018) Nivolumab with or without ipilimumab in patients with recurrent glioblastoma: results from exploratory phase 1 cohorts of CheckMate 143. Neuro Oncol 20:674–686. 10.1093/neuonc/nox208
28. Reardon DA, Omuro A, Brandes AA, Rieger J, Wick A, Sepulveda J, Phuphanich S, de Souza P, Ahluwalia MS, Lim M et al (2017) Randomized phase 3 study evaluating the efficacy and safety of nivolumab vs bevacizumab in patients with recurrent glioblastoma: CheckMate 143. WFNOS OS10.3. Neuro-oncology 19(suppl_3):iii21
29. Wen PY, Macdonald DR, Reardon DA, Cloughesy TF, Sorensen AG, Galanis E, Degroot J, Wick W, Gilbert MR, Lassman AB et al (2010) Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 28:1963–1972. 10.1200/JCO.2009.26.3541
30. Vennapusa B, Baker B, Kowanetz M, Boone J, Menzl I, Bruey JM, Fine G, Mariathasan S, McCaffery I, Mocci S et al (2018) Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab. Appl Immunohistochem Mol Morphol. 10.1097/PAI.0000000000000594
31. Chalmers ZR, Connelly CF, Fabrizio D, Gay L, Ali SM, Ennis R, Schrock A, Campbell B, Shlien A, Chmielecki J et al (2017) Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 10.1186/s13073-017-0424-2
32. Grant R, Brown PD (2016) Fatigue randomized controlled trials-how tired is “too tired” in patients undergoing glioma treatment? Neuro Oncol 18:759–760. 10.1093/neuonc/now052
33. Szopa W, Burley TA, Kramer-Marek G, Kaspera W (2017) Diagnostic and therapeutic biomarkers in glioblastoma: current status and future perspectives. Biomed Res Int 2017:8013575. 10.1155/2017/8013575
34. Palles C, Cazier JB, Howarth KM, Domingo E, Jones AM, Broderick P, Kemp Z, Spain SL, Guarino E, Salguero I et al (2013) Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas. Nat Genet 45:136–144. 10.1038/ng.2503
35. Johanns TM, Miller CA, Dorward IG, Tsien C, Chang E, Perry A, Uppaluri R, Ferguson C, Schmidt RE, Dahiya S et al (2016) Immunogenomics of hypermutated glioblastoma: a patient with germline POLE deficiency treated with checkpoint blockade Immunotherapy. Cancer Discov 6:1230–1236
36. Chamberlain MC, Johnston SK (2010) Salvage therapy with single agent bevacizumab for recurrent glioblastoma. J Neurooncol 96:259–269. 10.1007/s11060-009-9957-6
37. Reardon DA, Desjardins A, Peters KB, Gururangan S, Sampson JH, McLendon RE, Herndon JE 2nd, Bulusu A, Threatt S, Friedman AH et al (2012) Phase II study of carboplatin, irinotecan, and bevacizumab for bevacizumab naive, recurrent glioblastoma. J Neurooncol 107:155–164. 10.1007/s11060-011-0722-2
38. Huang Y, Goel S, Duda DG, Fukumura D, Jain RK (2013) Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 73:2943–2948. 10.1158/0008-5472.CAN-12-4354
39. Nduom EK, Wei J, Yaghi NK, Huang N, Kong LY, Gabrusiewicz K, Ling X, Zhou S, Ivan C, Chen JQ et al (2016) PD-L1 expression and prognostic impact in glioblastoma. Neuro Oncol 18:195–205. 10.1093/neuonc/nov172
40. Hirsch FR, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K, Richardson W, Towne P, Hanks D, Vennapusa B et al (2017) PD-L1 immunohistochemistry assays for lung cancer: results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 12:208–222
41. Seki M, Ushiyama C, Seta N, Abe K, Fukazawa T, Asakawa J, Takasaki Y, Hashimoto H (1998) Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. Arthritis Rheum 41:823–830. 10.1002/1529-0131(199805)41:53.0.CO;2-%23
42. Olnes MJ, Kotliarov Y, Biancotto A, Cheung F, Chen J, Shi R, Zhou H, Wang E, Tsang JS, Nussenblatt R et al (2016) Effects of systemically administered hydrocortisone on the human immunome. Sci Rep 6:23002. 10.1038/srep23002
43. Grossman SA, Ye X, Lesser G, Sloan A, Carraway H, Desideri S, Piantadosi S, NABTT CNS Consortium (2011) Immunosuppression in patients with high-grade gliomas treated with radiation and temozolomide. Clin Cancer Res 17:5473–5480. 10.1158/1078-0432.CCR-11-0774
44. Wong ET, Lok E, Gautam S, Swanson KD (2015) Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma. Br J Cancer 113:232–241. 10.1038/bjc.2015.238
45. Waitkus MS, Diplas BH, Yan H (2016) Isocitrate dehydrogenase mutations in gliomas. Neuro Oncol 18:16–26. 10.1093/neuonc/nov136
46. Kohanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor T, Chheda ZS, Downey KM, Watchmaker PB, Beppler C et al (2017) Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J Clin Invest 127:1425–1437
47. Dudley JC, Lin MT, Le DT, Eshleman JR (2016) Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res 22:813–820. 10.1158/1078-0432.CCR-15-1678
48. Yip S, Miao J, Cahill DP, Iafrate AJ, Aldape K, Nutt CL, Louis DN (2009) MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance. Clin Cancer Res 15:4622–4629. 10.1158/1078-0432.CCR-08-3012
49. van Thuijl HF, Mazor T, Johnson BE, Fouse SD, Aihara K, Hong C, Malmstrom A, Hallbeck M, Heimans JJ, Kloezeman JJ et al (2015) Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathol 129:597–607. 10.1007/s00401-015-1403-6
50. Howitt BE, Shukla SA, Sholl LM, Ritterhouse LL, Watkins JC, Rodig S, Stover E, Strickland KC, D’Andrea AD, Wu CJ et al (2015) Association of polymerase e-mutated and microsatellite-instable endometrial cancers with neoantigen load, number of tumor-infiltrating lymphocytes, and expression of PD-1 and PD-L1. JAMA Oncol 1:1319–1323. 10.1001/jamaoncol.2015.2151
51. Brandes AA, Franceschi E, Tosoni A, Blatt V, Pession A, Tallini G, Bertorelle R, Bartolini S, Calbucci F, Andreoli A et al (2008) MGMT promoter methylation status can predict the incidence and outcome of pseudoprogression after concomitant radiochemotherapy in newly diagnosed glioblastoma patients. J Clin Oncol 26:2192–2197. 10.1200/JCO.2007.14.8163
52. Okada H, Weller M, Huang R, Finocchiaro G, Gilbert MR, Wick W, Ellingson BM, Hashimoto N, Pollack IF, Brandes AA et al (2015) Immunotherapy response assessment in neuro-oncology: a report of the RANO working group. Lancet Oncol 16:e534–e542. 10.1016/S1470-2045(15)00088-1