Malignant pleural mesothelioma: an update

Hajj, Glaucia N. M.; Cavarson, Carolina H.; Pinto, Clóvis Antônio Lopes; Venturi, Gabriela; Navarro, João R.; Lima, Vladmir C. Cordeiro de

doi:10.36416/1806-3756/e20210129

Glaucia N. M. Hajj

Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.

Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil.

https://orcid.org/0000-0003-2342-7384

Carolina H. Cavarson

Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.

Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil.

https://orcid.org/0000-0002-3024-6576

Clóvis Antônio Lopes Pinto

Departamento de Patologia Anatômica, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.

https://orcid.org/0000-0003-1711-0081

Gabriela Venturi

Instituto International de Pesquisa, A.C. Camargo Cancer Center, São Paulo (SP), Brasil.

BP Mirante, São Paulo (SP), Brasil.

https://orcid.org/0000-0002-3764-7268

João R. Navarro

BP Mirante, São Paulo (SP), Brasil.

https://orcid.org/0000-0002-1159-4233

Vladmir C. Cordeiro de Lima

Instituto Nacional de Oncogenômica e Inovação Terapêutica, São Paulo (SP), Brasil.

Rede D’Or, São Paulo (SP), Brasil.

https://orcid.org/0000-0003-3955-1101

AUTHOR CONTRIBUTIONS

GNMH: final manuscript review and submission, manuscript draft elaboration, literature review, table and graphics construction, conceptualization.

CHC: manuscript draft elaboration, literature review.

CALP: manuscript draft elaboration, literature review, pathological specimens microphotographies.

GV: manuscript draft elaboration, literature review.

JRN: manuscript draft elaboration, literature review.

VCCL: final manuscript review, manuscript draft elaboration, literature review, table and graphics construction, treatment flow chart elaboration, conceptualization, oversight.

Mesothelial markers	Sensitivity	*Specificity versus* Lung adenocarcinoma**
Calretinin	> 90%	90-95%
CK5/6	75-100%	80-90%
WT1	70-95%	~100%
D2-40	90-100%	85%
Adenocarcinoma (epithelial markers)	Sensitivity	*Specificity versus* Malignant mesothelioma**
MOC31	95-100%	85-98%
BerEP4	95-100%	74-87%
BG8 (Lewis Y)	90-100%	93-97%
B72.3	25-85%	> 95%

Ref	Number of cases/samples	Techniques used	Main findings
Cheng et al.⁽⁵⁷57 Cheng JQ, Jhanwar SC, Klein WM, Bell DW, Lee WC, Altomare DA, et al. p16 alterations and deletion mapping of 9p21-p22 in malignant mesothelioma. Cancer Res. 1994;54(21):5547-51. PMid:7923195.⁾	40 cell lines and 23 primary tumors	Southern Blot and Targeted Seq of p16	Homozygous deletions on p16-INK in 85% both cell lines and 23% of tumors
Xio et al.⁽⁵⁸58 Xio S, Li D, Vijg J, Sugarbaker DJ, Corson JM, Fletcher JA. Codeletion of p15 and p16 in primary malignant mesothelioma. Oncogene. 1995;11(3):511-5. PMid:7630635.⁾	50 primary tumors	FISH for p15 and p16.	Co-deletion of p15 and p16 in 72% of cases.
Sekido et al.⁽⁵⁹59 Sekido Y, Pass HI, Bader S, Mew DJ, Christman MF, Gazdar AF, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55(6):1227-31. PMid:7882313.⁾	14 cell lines and 10 primary tumors	SSCP and Southern Blot for NF2	NF2 mutations in 41% of cases.
Bianchi et al.⁽⁶⁰60 Bianchi AB, Mitsunaga SI, Cheng JQ, Klein WM, Jhanwar SC, Seizinger B, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci USA. 1995;92(24):10854-8. http://dx.doi.org/10.1073/pnas.92.24.10854. PMid:7479897. http://dx.doi.org/10.1073/pnas.92.24.108... ⁾	15 cell lines and 7 primary tumors	SSCP; Targeted Seq for NF2	NF2 mutations in 53% of cases.
Björkqvist et al.⁽⁶¹61 Björkqvist A-M, Wolf M, Nordling S, Tammilehto L, Knuuttila A, Kere J, et al. Deletions at 14q in malignant mesothelioma detected by microsatellite marker analysis. Br J Cancer. 1999;81(7):1111-5. PMid:10584869.⁾	34 primary tumors	CGH array; Southern Blot.	loss in 4q, 6q and 14q and gain in 15q and 7p
Prins et al.⁽⁶²62 Prins JB, Williamson KA, Kamp MM, Van Hezik EJ, Van der Kwast TH, Hagemeijer A, et al. The gene for the cyclin-dependent-kinase-4 inhibitor, CDKN2A, is preferentially deleted in malignant mesothelioma. Int J Cancer. 1997;95(4):649-53. PMid:9466670.⁾	12 cell lines	PCR; FISH	Chromosome 9 deletion including CDKN2A but not CDKN2B.
Taniguchi et al.⁽⁶³63 Taniguchi T, Karnan S, Fukui T, Yokoyama T, Tagawa H, Yokoi K, et al. Genomic profiling of malignant pleural mesothelioma with array-based comparative genomic hybridization shows frequent non-random chromosomal alteration regions including JUN amplification on 1p32. Cancer Sci. 2007;98(3):438-46. http://dx.doi.org/10.1111/j.1349-7006.2006.00386.x. PMid:17270034. http://dx.doi.org/10.1111/j.1349-7006.20... ⁾	17 primary tumors and 9 cell lines	CGH array; Southern Blot; Targeted Seq of NF2;	Gains in 1q, 5p, 7p, 8q24 and 20p; Loss in 1p36.33, 1p36.1, 1p21.3, 3p21.3, 4q22, 6q25, 9p21.3, 10p, 13q33.2, 14q32.13, 18q and 22q.
Ivanov et al.⁽⁶⁴64 Ivanov SV, Miller J, Lucito R, Tang C, Ivanova AV, Pei J, et al. Genomic events associated with progression of pleural malignant mesothelioma. Int J Cancer. 2009;124(3):589-99. http://dx.doi.org/10.1002/ijc.23949. PMid:18973227. http://dx.doi.org/10.1002/ijc.23949... ⁾	22 primary tumors	CNA array	Deletions in 22q12.2, 19q13.32 and 17p13.1 in 55-74% and gain in 5p, 18q, 8q and 17q in 23-55% of cases.
Cheung et al.⁽⁶⁵65 Cheung M, Pei J, Pei Y, Jhanwar SC, Pass HI, Testa JR. The promyelocytic leukemia zinc-finger gene, PLZF, is frequently downregulated in malignant mesothelioma cells and contributes to cell survival. Oncogene. 2010;29(11):1633-40. http://dx.doi.org/10.1038/onc.2009.455. PMid:20010871. http://dx.doi.org/10.1038/onc.2009.455... ⁾	22 cell lines	CNA array	deletions of CDKN2A/ARF and CDKN2B, 1p36, 1p22, 3p21-22, 4q13-34, 11q23, 13q12-13, 14q32, 15q15, 18q12 and 22q12 in 55-90%
Takeda et al.⁽⁶⁶66 Takeda M, Kasai T, Enomoto Y, Takano M, Morita K, Kadota E, et al. Genomic gains and losses in malignant mesothelioma demonstrated by FISH analysis of paraffin-embedded tissues. J Clin Pathol. 2012;65(1):77-82. http://dx.doi.org/10.1136/jclinpath-2011-200208. PMid:22081786. http://dx.doi.org/10.1136/jclinpath-2011... ⁾	40 primary tumors	9p21 FISH	9p21 deletion in 35 of 40 cases (88%)
Bott et al.⁽⁶⁷67 Bott M, Brevet M, Taylor BS, Shimizu S, Ito T, Wang L, et al. The nuclear deubiquitinase BAP1 is commonly inactivated by somatic mutations and 3p21.1 losses in malignant pleural mesothelioma. Nat Genet. 2011;43(7):668-72. http://dx.doi.org/10.1038/ng.855. PMid:21642991. http://dx.doi.org/10.1038/ng.855... ⁾	53 primary tumors	CGH array, FISH; Targeted Seq.	Deletions at 9p21, 22q and 3p21. Mutations in BAP1, NF2, LATS1
Yoshikawa et al. ⁽⁶⁸68 Yoshikawa Y, Sato A, Tsujimura T, Emi M, Morinaga T, Fukuoka K, et al. Frequent inactivation of the BAP1 gene in epithelioid-type malignant mesothelioma. Cancer Sci. 2012;103(5):868-74. http://dx.doi.org/10.1111/j.1349-7006.2012.02223.x. PMid:22321046. http://dx.doi.org/10.1111/j.1349-7006.20... ⁾	23 primary tumors	Targeted Seq of BAP1	biallelic BAP1 gene alterations in 14 of 23 MMs (61%)
Guo et al.⁽⁶⁹69 Guo G, Chmielecki J, Goparaju C, Heguy A, Dolgalev I, Carbone M, et al. Whole-exome sequencing reveals frequent genetic alterations in BAP1, NF2, CDKN2A, and CUL1 in malignant pleural mesothelioma. Cancer Res. 2015;75(2):264-9. http://dx.doi.org/10.1158/0008-5472.CAN-14-1008. PMid:25488749. http://dx.doi.org/10.1158/0008-5472.CAN-... ⁾	22 primary tumors	Whole-exome Seq	Major changes in copy numbers: BAP1, NF2, CDKN2A, CUL1.
Lo Iacono et al.⁽⁷⁰70 Lo Iacono M, Monica V, Righi L, Grosso F, Libener R, Vatrano S, et al. Targeted next-generation sequencing of cancer genes in advanced stage malignant pleural mesothelioma: a retrospective study. J Thorac Oncol. 2015;10(3):492-9. http://dx.doi.org/10.1097/JTO.0000000000000436. PMid:25514803. http://dx.doi.org/10.1097/JTO.0000000000... ⁾	123 primary tumors	Targeted NGS of 52 genes	Alterations in p53/DNA repair (TP53, SMACB1, and BAP1) and PI3K–AKT pathways (PDGFRA, KIT, KDR, HRAS, PIK3CA, STK11, and NF2).
Nasu et al.⁽⁷¹71 Nasu M, Emi M, Pastorino S, Tanji M, Powers A, Luk H, et al. High incidence of somatic BAP1 alterations in sporadic malignant mesothelioma. J Thorac Oncol. 2015;10(4):565-76. http://dx.doi.org/10.1097/JTO.0000000000000471. PMid:25658628. http://dx.doi.org/10.1097/JTO.0000000000... ⁾	22 primary tumors	Targeted BAP1 Sanger Seq.; MLPA	alteration of BAP1 in 63.6% of cases
Borczuk et al.⁽⁷²72 Borczuk AC, Pei J, Taub RN, Levy B, Nahum O, Chen J, et al. Genome-wide analysis of abdominal and pleural malignant mesothelioma with DNA arrays reveals both common and distinct regions of copy number alteration. Cancer Biol Ther. 2016;17(3):328-35. http://dx.doi.org/10.1080/15384047.2016.1145850. PMid:26853494. http://dx.doi.org/10.1080/15384047.2016.... ⁾	48 peritoneal and 41 pleural tumors	CNA array	Loss in BAP1, CDKN2A and NF2 in both tumor sites. Copy number gain were more common in peritoneum, loss were more common in pleura
Kato et al.⁽⁷³73 Kato S, Tomson BN, Buys TPH, Elkin SK, Carter JL, Kurzrock R. Genomic landscape of malignant mesotheliomas. Mol Cancer Ther. 2016;15(10):2498-507. http://dx.doi.org/10.1158/1535-7163.MCT-16-0229. PMid:27507853. http://dx.doi.org/10.1158/1535-7163.MCT-... ⁾	42 primary tumors	Targeted NGS of 236 genes	Alterations in BAP1 (47,6%), NF2 (38,1%) and CDKN2A/B (35,7%).
Kang et al.⁽⁷⁴74 Kang HC, Kim HK, Lee S, Mendez P, Kim W, Woodard G, et al. Whole exome and targeted deep sequencing identify genome- wide allelic loss and frequent SETDB1 mutations in malignant pleural mesotheliomas. Oncotarget. 2016;7(7):8321-31. http://dx.doi.org/10.18632/oncotarget.7032. PMid:26824986. http://dx.doi.org/10.18632/oncotarget.70... ⁾	78 primary tumors	Targeted Seq of SETDB1	Mutations in 7 patients
Ugurluer et al.⁽⁷⁵75 Ugurluer G, Chang K, Gamez ME, Arnett AL, Jayakrishnan R, Miller RC, et al. Genome-based mutational analysis by next generation sequencing in patients with malignant pleural and peritoneal mesothelioma. Anticancer Res. 2016;36(5):2331-8. PMid:27127140.⁾	11 primary tumors	Targeted NGS of 236 mutations	Mutations in 86% of pleural and 50% of peritoneal cases. Most mutated genes were BAP1 (36%), CDKNA2A/B (27%) and NF2 (27%).
Chirac et al.⁽⁷⁶76 Chirac P, Maillet D, Leprêtre F, Isaac S, Glehen O, Figeac M, et al. Genomic copy number alterations in 33 malignant peritoneal mesothelioma analyzed by comparative genomic hybridization array. Hum Pathol. 2016;55:72-82. http://dx.doi.org/10.1016/j.humpath.2016.04.015. PMid:27184482. http://dx.doi.org/10.1016/j.humpath.2016... ⁾	33 peritoneal primary tumors	CGH array	Genomic pattern similar to pleural mesothelioma: loss of 3p21, 9p21, and 22q12. novel CNA included 15q26.2 and 8p11.22
Bueno et al.⁽⁷⁷77 Bueno R, Stawiski EW, Goldstein LD, Durinck S, De Rienzo A, Modrusan Z, et al. Comprehensive genomic analysis of malignant pleural mesothelioma identifies recurrent mutations, gene fusions and splicing alterations. Nat Genet. 2016;48(4):407-16. http://dx.doi.org/10.1038/ng.3520. PMid:26928227. http://dx.doi.org/10.1038/ng.3520... ⁾	216 primary tumors	Whole Exome Seq, Targeted NGS	BAP1, NF2, TP53, SETD2, DDX3X, ULK2, RYR2, CFAP45, SETDB1 and DDX51 significantly mutated genes. Gene fusion and splice alterations in NF2, BAP1 and SETD2. Alterations in Hippo, mTOR, histone methylation, RNA helicase and p53 signaling pathways.
Yoshikawa et al.⁽⁷⁸78 Yoshikawa Y, Emi M, Hashimoto-Tamaoki T, Ohmuraya M, Sato A, Tsujimura T, et al. High-density array-CGH with targeted NGS unmask multiple noncontiguous minute deletions on chromosome 3p21 in mesothelioma. Proc Natl Acad Sci USA. 2016;113(47):13432-7. http://dx.doi.org/10.1073/pnas.1612074113. PMid:27834213. http://dx.doi.org/10.1073/pnas.161207411... ⁾	33 primary tumors	CGH array for the 3p21 region; Targeted NGS of 4 genes	biallelic gene inactivation in SETD2 (9 of 33, 27%), BAP1 (16 of 33, 48%), PBRM1 (5 of 33, 15%), and SMARCC1 (2 of 33, 6%)
Desmeules et al.⁽⁷⁹79 Desmeules P, Joubert P, Zhang L, Al-Ahmadie HA, Fletcher CD, Vakiani E, et al. A subset of malignant mesotheliomas in young adults are associated with recurrent EWSR1/FUS-ATF1 fusions. Am J Surg Pathol. 2017;41(7):980-8. http://dx.doi.org/10.1097/PAS.0000000000000864. PMid:28505004. http://dx.doi.org/10.1097/PAS.0000000000... ⁾	25 primary tumors	FISH	Identification of a EWSR1/FUS-ATF1 gene fusion in 4 cases
Hung et al.⁽⁸⁰80 Hung YP, Dong F, Watkins JC, Nardi V, Bueno R, Dal Cin P, et al. Identification of ALK rearrangements in malignant peritoneal mesothelioma. JAMA Oncol. 2018;4(2):235-8. http://dx.doi.org/10.1001/jamaoncol.2017.2918. PMid:28910456. http://dx.doi.org/10.1001/jamaoncol.2017... ⁾	88 peritoneal primary tumors	FISH; Targeted NGS for ALK	ALK rearrangements in 3 cases with ATG16L1, STRN, and TPM1
Kim et al.⁽⁹9 Kim J, Bhagwandin S, Labow DM. Malignant peritoneal mesothelioma: a review. Ann Transl Med. 2017;5(11):236. http://dx.doi.org/10.21037/atm.2017.03.96. PMid:28706904. http://dx.doi.org/10.21037/atm.2017.03.9... ⁾	13 peritoneal primary tumors	Targeted NGS of 510 genes;	Bi-allelic inactivation of BAP1 (9/13 cases), mutation in NF2 (3/13); SETD2 (2/13) e DDX3X (2/13).
Hmeljak et al.⁽⁸¹81 Hmeljak J, Sanchez-Vega F, Hoadley KA, Shih J, Stewart C, Heiman D, et al. Integrative molecular characterization of malignant pleural mesothelioma. Cancer Discov. 2018;8(12):1548-65. http://dx.doi.org/10.1158/2159-8290.CD-18-0804. PMid:30322867. http://dx.doi.org/10.1158/2159-8290.CD-1... ⁾	74 primary tumors	Whole Exome Seq.; CNA array	Inactivating alterations by mutation and CNA in: BAP1, CDKN2A, NF2, TP53, LATS2, and SETD2. Novel molecular subtype (3% of cases) genomic near-haploidization and TP53 and SETDB1 mutations
Hassan et al.⁽⁸²82 Hassan R, Morrow B, Thomas A, Walsh T, Lee MK, Gulsuner S, et al. Inherited predisposition to malignant mesothelioma and overall survival following platinum chemotherapy. Proc Natl Acad Sci USA. 2019;116(18):9008-13. http://dx.doi.org/10.1073/pnas.1821510116. PMid:30975761. http://dx.doi.org/10.1073/pnas.182151011... ⁾	239 genomic DNA from MM patients	Targeted NGS of 73 genes	12% of cases had germline mutations: 16 in BAP1 and 12 distributed among CHEK2, PALB2, BRCA2, MLH1, POT1, TP53, and MRE11A
Nastase et al.⁽⁸³83 Nastase A, Mandal A, Lu SK, Anbunathan H, Morris-Rosendahl D, Zhang YZ, et al. Multiple therapeutic pathways in malignant mesothelioma identified by genomic mapping. medRxiv. 2020. In press.⁾	121 primary tumors	CNA array, Whole Exome Seq.;	CDKN2A deletion in 60% of tumours; BAP1 mutated or deleted in 54%; RASSF7 amplification in 33%; RB1 deleted or mutated in 26%; NF2 mutated in 20%; TP53 mutated in 8%; SETD2 in 6%; DDX3X in 5% and LATS2 in 5%.
Quetel et al.⁽⁸⁴84 Quetel L, Meiller C, Assié JB, Blum Y, Imbeaud S, Montagne F, et al. Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival. Mol Oncol. 2020;14(6):1207-23. http://dx.doi.org/10.1002/1878-0261.12651. PMid:32083805. http://dx.doi.org/10.1002/1878-0261.1265... ⁾	266 primary tumors	Targeted NGS 21 genes	TERT promoter, NF2, and TP53 mutations associated w/ worse survival.

Trial	Phase	Arms	N	ORR (%)	PFS Median (Months)	OS Median (Months)	PD-L1 Expression
DETERMINE	II	Tremelimumab	569	5	2.8	7.7	NE
KEYNOTE-028⁽¹⁵¹151 Alley EW, Lopez J, Santoro A, Morosky A, Saraf S, Piperdi B, et al. Clinical safety and activity of pembrolizumab in patients with malignant pleural mesothelioma (KEYNOTE-028): preliminary results from a non-randomised, open-label, phase 1b trial. Lancet Oncol. 2017;18(5):623-30. http://dx.doi.org/10.1016/S1470-2045(17)30169-9. PMid:28291584. http://dx.doi.org/10.1016/S1470-2045(17)... ⁾	IB	Pembrolizumab	25	20	5.4	18	All tumors were PD-L1+
Kindler et al.⁽¹⁵²152 Kindler H, Karrison T, Tan YHC, Rose B, Ahmad M, Strausand C, et al. Phase II Trial of Pembrolizumab in Patients with Malignant Mesothelioma (MM): Interim Analysis. Journal of Thoracic Oncology. 2017;12(1):293-294.⁾	II	Pembrolizumab	35	21	6.2	NR	NA
NivoMes⁽¹⁵³153 Quispel-Janssen J, Noort V, Vries JF, Zimmerman M, Lalezari F, Thunnissen E, et al. Programmed Death 1 blockade with nivolumab in patients with recurrent malignant pleural mesothelioma. J Thorac Oncol. 2018;13(10):1569-76. http://dx.doi.org/10.1016/j.jtho.2018.05.038. PMid:29908324. http://dx.doi.org/10.1016/j.jtho.2018.05... ⁾	II	Nivolumab	34	24	2.6	11.8	Trend to higher ORR
MERIT⁽¹⁵⁴154 Okada M, Kijima T, Aoe K, Kato T, Fujimoto N, Nakagawa K, et al. Clinical efficacy and safety of nivolumab: results of a multicenter, open-label, single-arm, japanese phase ii study in Malignant Pleural Mesothelioma (MERIT). Clin Cancer Res. 2019;25(18):5485-92. http://dx.doi.org/10.1158/1078-0432.CCR-19-0103. PMid:31164373. http://dx.doi.org/10.1158/1078-0432.CCR-... ⁾	II	Nivolumab	34	29	6.1	17.3	Improved PFS and OS
JAVELIN⁽¹⁵⁵155 Hassan R, Thomas A, Nemunaitis JJ, Patel MR, Bennouna J, Chen FL, et al. Efficacy and safety of avelumab treatment in patients with advanced unresectable mesothelioma. JAMA Oncol. 2019;5(3):351-7. http://dx.doi.org/10.1001/jamaoncol.2018.5428. PMid:30605211. http://dx.doi.org/10.1001/jamaoncol.2018... ⁾	IB	Avelumab	53	9.4	4.3	NR	Trend to improved PFS
NIBIT-MESO-1⁽¹⁵⁶156 Calabrò L, Morra A, Giannarelli D, Amato G, D’Incecco A, Covre A, 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. http://dx.doi.org/10.1016/S2213-2600(18)... ⁾	II	Tremelimumab + durvalumab	40	25	5.7	16.6	Improved ORR, OS and PFS
INITIATE⁽¹⁵⁷157 Disselhorst MJ, Quispel-Janssen J, Lalezari F, Monkhorst K, de Vries JF, Noort V, et al. Ipilimumab and nivolumab in the treatment of recurrent malignant pleural mesothelioma (INITIATE): results of a prospective, single-arm, phase 2 trial. Lancet Respir Med. 2019;7(3):260-70. http://dx.doi.org/10.1016/S2213-2600(18)30420-X. PMid:30660511. http://dx.doi.org/10.1016/S2213-2600(18)... ⁾	II	Nivolumab + ipilimumab	36	29	6.2	NR	Improved ORR
MAPS2	II (randomized)	Nivolumab + ipilimumab Nivolumab	125	28	5.6	15.9	No association with OS or PFS
MAPS2	II (randomized)	Nivolumab + ipilimumab Nivolumab	125	9	4.0	11.9	No association with OS or PFS
PROMISE	III	Pembrolizumab Gemcitabine or Vinorelbine	144	20	2.5	10.7	NA
PROMISE	III	Pembrolizumab Gemcitabine or Vinorelbine	144	20	3.4	12.4	NA
CONFIRM	III	Nivolumab BSC	332	NR	4.2	9.1	NA
CONFIRM	III	Nivolumab BSC	332	NR	2.8	9.7	NA

TITLE	PRIMARY ID	CLINICALTRIALS ID
PHASE III RANDOMIZED TRIAL OF PLEURECTOMY/DECORTICATION PLUS CHEMOTHERAPY WITH OR WITHOUT ADJUVANT HEMITHORACIC INTENSITY-MODULATED PLEURAL RADIATION THERAPY (IMPRINT) FOR MPM.	NRG-LU006	NCT04158141
RANDOMIZED, DOUBLE-BLIND, PHASE 2/3 STUDY IN SUBJECTS WITH MPM TO ASSESS ADI-PEG 20 WITH PEMETREXED AND CISPLATIN (ATOMIC-MESO PHASE 2/3 STUDY).	POLARIS2015-003	NCT02709512
A PHASE III, RANDOMIZED, OPEN LABEL TRIAL OF NIVOLUMAB IN COMBINATION WITH IPILIMUMAB VERSUS PEMETREXED WITH CISPLATIN OR CARBOPLATIN AS FIRST LINE THERAPY IN UNRESECTABLE MPM	CA209-743	NCT02899299
A MULTICENTRE RANDOMISED PHASE III TRIAL COMPARING ATEZOLIZUMAB PLUS BEVACIZUMAB AND STANDARD CHEMOTHERAPY VERSUS BEVACIZUMAB AND STANDARD CHEMOTHERAPY AS FIRST-LINE TREATMENT FOR ADVANCED MPM.	ETOP 13-18	NCT03762018
A RANDOMIZED, OPEN-LABEL PHASE II/III STUDY WITH DENDRITIC CELLS LOADED WITH ALLOGENEIC TUMOUR CELL LYSATE (PHERALYS) IN SUBJECTS WITH MESOTHELIOMA AS MAINTENANCE TREATMENT (MESOPHER) AFTER CHEMOTHERAPY.	MM04	NCT03610360
A PHASE II/III RANDOMIZED STUDY OF PEMBROLIZUMAB IN PATIENTS WITH ADVANCED MPM.	IFCT-1901	NCT02784171

[1] AUTHOR CONTRIBUTIONS

GNMH: final manuscript review and submission, manuscript draft elaboration, literature review, table and graphics construction, conceptualization.

CHC: manuscript draft elaboration, literature review.

CALP: manuscript draft elaboration, literature review, pathological specimens microphotographies.

GV: manuscript draft elaboration, literature review.

JRN: manuscript draft elaboration, literature review.

VCCL: final manuscript review, manuscript draft elaboration, literature review, table and graphics construction, treatment flow chart elaboration, conceptualization, oversight.

Brasil

Brasil

Malignant pleural mesothelioma: an update

ABSTRACT