Morphological, immune and genetic features in biopsy sample associated with the efficacy of pembrolizumab in patients with non-squamous non-small cell lung cancer.
Adenocarcinoma of Lung
/ drug therapy
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
B7-H1 Antigen
/ antagonists & inhibitors
Biomarkers, Tumor
/ genetics
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Humans
Lung Neoplasms
/ drug therapy
Male
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Prognosis
Retrospective Studies
Survival Rate
Exome Sequencing
Lung cancer
Morphological features
PD-L1
Pembrolizumab
TMB
Journal
Journal of cancer research and clinical oncology
ISSN: 1432-1335
Titre abrégé: J Cancer Res Clin Oncol
Pays: Germany
ID NLM: 7902060
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
05
08
2020
accepted:
24
09
2020
pubmed:
1
10
2020
medline:
26
3
2021
entrez:
30
9
2020
Statut:
ppublish
Résumé
The usefulness of the histopathology of biopsy samples for predicting the efficacy of immunotherapy in non-squamous, non-small cell lung cancer (NSq NSCLC) patients remains unclear. We retrospectively investigated the associations between the histopathological features in biopsy samples and survival outcomes in advanced NSq NSCLC patients receiving pembrolizumab. NSq NSCLC was classified histopathologically as morphological adenocarcinoma or non-small cell carcinoma (NSCC: absence of definitive features of either adenocarcinoma or a squamous morphology). We investigated the association between the tumor morphological features and immune/genetic features by examining the tumor PD-L1 expression and tumor mutation burden (TMB). Among 33 advanced NSq NSCLC patients with tumor PD-L1 scores ≥ 50% receiving pembrolizumab as first-line therapy, a biopsy diagnosis of NSCC was associated with a significantly longer progression-free survival [median 16.8 vs. 2.3 months; hazard ratio (HR) 0.26; 95% CI 0.10-0.62, P = 0.01] and overall survival (median NR vs. 10.1 months; HR 0.35; 0.12-0.97, P = 0.04) as compared to that of morphological adenocarcinoma. In an analysis of 367 biopsy samples, the NSCC group showed a higher percentage of samples with PD-L1 scores ≥ 50% than the morphological adenocarcinoma group (35% vs. 10%). The NSCC group (n = 8) also showed a significantly higher TMB than the morphological adenocarcinoma group (n = 7) (median 236 vs. 25 mutations/whole exome, P = 0.01). Absence of definitive morphological features in a biopsy sample could be a useful predictor of the efficacy of pembrolizumab in NSq NSCLC patients with tumor PD-L1 scores ≥ 50%, as these tumors are likely to show high tumor PD-L1 expression and high TMB.
Identifiants
pubmed: 32997195
doi: 10.1007/s00432-020-03413-5
pii: 10.1007/s00432-020-03413-5
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antineoplastic Agents, Immunological
0
B7-H1 Antigen
0
Biomarkers, Tumor
0
CD274 protein, human
0
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1227-1237Références
Aguilar EJ, Ricciuti B, Gainor JF, Kehl KL, Kravets S, Dahlberg S, Nishino M, Sholl LM, Adeni A, Subegdjo S, Khosrowjerdi S, Peterson RM, Digumarthy S, Liu C, Sauter J, Rizvi H, Arbour KC, Carter BW, Heymach JV, Altan M, Hellmann MD, Awad MM (2019) Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression. Ann Oncol 30:1653–1659
doi: 10.1093/annonc/mdz288
Carbone DP, Reck M, Paz-Ares L, Creelan B, Horn L, Steins M, Felip E, van den Heuvel MM, Ciuleanu TE, Badin F, Ready N, Hiltermann TJN, Nair S, Juergens R, Peters S, Minenza E, Wrangle JM, Rodriguez-Abreu D, Borghaei H, Blumenschein GR Jr, Villaruz LC, Havel L, Krejci J, Corral Jaime J, Chang H, Geese WJ, Bhagavatheeswaran P, Chen AC, Socinski MA (2017) First-line nivolumab in stage IV or recurrent non-small-cell lung cancer. N Engl J Med 376:2415–2426
doi: 10.1056/NEJMoa1613493
Dong ZY, Zhang C, Li YF, Su J, Xie Z, Liu SY, Yan LX, Chen ZH, Yang XN, Lin JT, Tu HY, Yang JJ, Zhou Q, Sun YL, Zhong WZ, Wu YL (2018) Genetic and immune profiles of solid predominant lung adenocarcinoma reveal potential immunotherapeutic strategies. J Thorac Oncol 13:85–96
doi: 10.1016/j.jtho.2017.10.020
Gandhi L, Rodríguez-Abreu D, Gadgeel S, Esteban E, Felip E, De Angelis F, Domine M, Clingan P, Hochmair MJ, Powell SF, Cheng SYS, Bischoff HG, Peled N, Grossi F, Jennens RR, Reck M, Hui R, Garon EB, Boyer M, Rubio-Viqueira B, Novello S, Kurata T, Gray JE, Vida J, Wei Z, Yang J, Raftopoulos H, Pietanza MC, Garassino MC (2018) Pembrolizumab plus chemotherapy in metastatic non–small-cell lung cancer. N Engl J Med 378:2078–2092
doi: 10.1056/NEJMoa1801005
Hellmann MD, Ciuleanu TE, Pluzanski A, Lee JS, Otterson GA, Audigier-Valette C, Minenza E, Linardou H, Burgers S, Salman P, Borghaei H, Ramalingam SS, Brahmer J, Reck M, O'Byrne KJ, Geese WJ, Green G, Chang H, Szustakowski J, Bhagavatheeswaran P, Healey D, Fu Y, Nathan F, Paz-Ares L (2018) Nivolumab plus ipilimumab in lung cancer with a high tumor mutational burden. N Engl J Med 378:2093–2104
doi: 10.1056/NEJMoa1801946
Ikematsu Y, Yoneshima Y, Ijichi K, Tanaka K, Harada T, Oda Y, Nakanishi Y, Okamoto I (2017) Marked response to pembrolizumab in a patient with pulmonary pleomorphic carcinoma highly positive for PD-L1. Lung Cancer 112:230–231
doi: 10.1016/j.lungcan.2017.07.020
Kim S, Kim MY, Koh J, Go H, Lee DS, Jeon YK, Chung DH (2015) Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: comparison of sarcomatous and carcinomatous areas. Euro J Cancer (Oxford, England: 1990) 51:2698–2707
Lang D, Huemer F, Rinnerthaler G, Horner A, Wass R, Brehm E, Akbari K, Granitz M, Hutarew G, Kaiser B, Greil R, Lamprecht B (2019) Therapy line and associated predictors of response to PD-1/PD-L1-inhibitor monotherapy in advanced non-small-cell lung cancer: a retrospective bi-centric cohort study. Targeted Oncol 14:707–717
doi: 10.1007/s11523-019-00679-9
Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B, Diaz LA Jr (2015) PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372:2509–2520
doi: 10.1056/NEJMoa1500596
Matsuzawa R, Kirita K, Kuwata T, Umemura S, Matsumoto S, Fujii S, Yoh K, Kojima M, Niho S, Ohmatsu H, Ochiai A, Tsuboi M, Goto K, Ishii G (2016) Factors influencing the concordance of histological subtype diagnosis from biopsy and resected specimens of lung adenocarcinoma. Lung Cancer 94:1–6
doi: 10.1016/j.lungcan.2016.01.009
Miyazawa T, Marushima H, Saji H, Kojima K, Hoshikawa M, Takagi M, Nakamura H (2019) PD-L1 expression in non-small-cell lung cancer including various adenocarcinoma subtypes. Ann Thoracic Cardiovasc Surg 25:1–9
doi: 10.5761/atcs.oa.18-00163
Ott PA, Bang YJ, Piha-Paul SA, Razak ARA, Bennouna J, Soria JC, Rugo HS, Cohen RB, O'Neil BH, Mehnert JM, Lopez J, Doi T, van Brummelen EMJ, Cristescu R, Yang P, Emancipator K, Stein K, Ayers M, Joe AK, Lunceford JK (2019) T-Cell-Inflamed gene-expression profile, programmed death ligand 1 expression, and tumor mutational burden predict efficacy in patients treated with pembrolizumab across 20 cancers: KEYNOTE-028. J Clin Oncol 37:318–327.
Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM, Investigators K (2018) Pembrolizumab plus chemotherapy for squamous non-small-cell lung cancer. N Engl J Med 379:2040–2051
doi: 10.1056/NEJMoa1810865
Pelosi G, Haspinger ER, Bimbatti M, Leone G, Paolini B, Fabbri A, Tamborini E, Perrone F, Testi A, Garassino M, Maisonneuve P, de Braud F, Pilotti S, Pastorino U (2014) Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases. Int J Surg Pathol 22:136–148
doi: 10.1177/1066896913511527
Ready N, Hellmann MD, Awad MM, Otterson GA, Gutierrez M, Gainor JF, Borghaei H, Jolivet J, Horn L, Mates M, Brahmer J, Rabinowitz I, Reddy PS, Chesney J, Orcutt J, Spigel DR, Reck M, O'Byrne KJ, Paz-Ares L, Hu W, Zerba K, Li X, Lestini B, Geese WJ, Szustakowski JD, Green G, Chang H, Ramalingam SS (2019) First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568): outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers. J Clin Oncol 37:992–1000
doi: 10.1200/JCO.18.01042
Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR, Investigators K (2016) Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung cancer. N Engl J Med 375:1823–1833
doi: 10.1056/NEJMoa1606774
Rekhtman N, Ang DC, Riely GJ, Ladanyi M, Moreira AL (2013) KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol 26:1307–1319
doi: 10.1038/modpathol.2013.74
Rizvi H, Sanchez-Vega F, La K, Chatila W, Jonsson P, Halpenny D, Plodkowski A, Long N, Sauter JL, Rekhtman N, Hollmann T, Schalper KA, Gainor JF, Shen R, Ni A, Arbour KC, Merghoub T, Wolchok J, Snyder A, Chaft JE, Kris MG, Rudin CM, Socci ND, Berger MF, Taylor BS, Zehir A, Solit DB, Arcila ME, Ladanyi M, Riely GJ, Schultz N, Hellmann MD (2018) Molecular determinants of response to anti-programmed cell death (PD)-1 and anti-programmed death-ligand 1 (PD-L1) blockade in patients with non-small-cell lung cancer profiled with targeted next-generation sequencing. J Clin Oncol 36:633–641
doi: 10.1200/JCO.2017.75.3384
Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS, Miller ML, Rekhtman N, Moreira AL, Ibrahim F, Bruggeman C, Gasmi B, Zappasodi R, Maeda Y, Sander C, Garon EB, Merghoub T, Wolchok JD, Schumacher TN, Chan TA (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science (New York, NY) 348:124–128
doi: 10.1126/science.aaa1348
Roszik J, Haydu LE, Hess KR, Oba J, Joon AY, Siroy AE, Karpinets TV, Stingo FC, Baladandayuthapani V, Tetzlaff MT, Wargo JA, Chen K, Forget MA, Haymaker CL, Chen JQ, Meric-Bernstam F, Eterovic AK, Shaw KR, Mills GB, Gershenwald JE, Radvanyi LG, Hwu P, Futreal PA, Gibbons DL, Lazar AJ, Bernatchez C, Davies MA, Woodman SE (2016) Novel algorithmic approach predicts tumor mutation load and correlates with immunotherapy clinical outcomes using a defined gene mutation set. BMC Med 14:168
doi: 10.1186/s12916-016-0705-4
Shiran I, Heller E, Jessel S, Kamer I, Daniel-Meshulam I, Navon R, Urban D, Onn A, Bar J (2017) Non-small-cell lung cancer patients with adenocarcinoma morphology have a better outcome compared with patients diagnosed with non-small-cell lung cancer favor adenocarcinoma. Clin Lung Cancer 18:316–323.e311
doi: 10.1016/j.cllc.2017.01.009
Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA 68:7–30.
Takada K, Okamoto T, Shoji F, Shimokawa M, Akamine T, Takamori S, Katsura M, Suzuki Y, Fujishita T, Toyokawa G, Morodomi Y, Okano S, Oda Y, Maehara Y (2016) Clinical significance of PD-L1 protein expression in surgically resected primary lung adenocarcinoma. J Thorac Oncol 11:1879–1890
doi: 10.1016/j.jtho.2016.06.006
Travis WD, Brambilla E, Burke AP, Marx A, (Eds.) AGN (2015) WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart, fourth ed edn. Internatilnal Agency for Reserch on Cancer, Lyon
Travis WD, Brambilla E, Noguchi M, Nicholson AG, Geisinger KR, Yatabe Y, Beer DG, Powell CA, Riely GJ, Van Schil PE, Garg K, Austin JH, Asamura H, Rusch VW, Hirsch FR, Scagliotti G, Mitsudomi T, Huber RM, Ishikawa Y, Jett J, Sanchez-Cespedes M, Sculier JP, Takahashi T, Tsuboi M, Vansteenkiste J, Wistuba I, Yang PC, Aberle D, Brambilla C, Flieder D, Franklin W, Gazdar A, Gould M, Hasleton P, Henderson D, Johnson B, Johnson D, Kerr K, Kuriyama K, Lee JS, Miller VA, Petersen I, Roggli V, Rosell R, Saijo N, Thunnissen E, Tsao M, Yankelewitz D (2011) International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6:244–285
doi: 10.1097/JTO.0b013e318206a221
Ujiie H, Kadota K, Chaft JE, Buitrago D, Sima CS, Lee MC, Huang J, Travis WD, Rizk NP, Rudin CM, Jones DR, Adusumilli PS (2015) Solid predominant histologic subtype in resected stage I lung adenocarcinoma is an independent predictor of early, extrathoracic, multisite recurrence and of poor postrecurrence survival. J Clin Oncol 33:2877–2884
doi: 10.1200/JCO.2015.60.9818
Warth A, Muley T, Meister M, Stenzinger A, Thomas M, Schirmacher P, Schnabel PA, Budczies J, Hoffmann H, Weichert W (2012) The novel histologic international association for the study of lung cancer/American thoracic society/European respiratory society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 30:1438–1446
doi: 10.1200/JCO.2011.37.2185
Willis C, Fiander M, Tran D, Korytowsky B, Thomas JM, Calderon F, Zyczynski TM, Brixner D, Stenehjem DD (2019) Tumor mutational burden in lung cancer: a systematic literature review. Oncotarget 10:6604–6622
doi: 10.18632/oncotarget.27287