Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer

被引：129

作者：

Landi, Lorenza ^{[1
]}

D'Inca, Federica ^{[2
]}

Gelibter, Alain ^{[3
]}

Chiari, Rita ^{[4
]}

Grossi, Francesco ^{[5
]}

Delmonte, Angelo ^{[6
]}

Passaro, Antonio ^{[7
]}

Signorelli, Diego ^{[8
]}

Gelsomino, Francesco ^{[9
]}

Galetta, Domenico ^{[10
]}

Giannarelli, Diana ^{[11
]}

Parra, Hector Soto ^{[12
]}

Minuti, Gabriele ^{[13
]}

Tiseo, Marcello ^{[14
]}

Migliorino, Maria Rita ^{[15
]}

Cognetti, Francesco ^{[11
]}

Toschi, Luca ^{[16
]}

Bidoli, Paolo ^{[17
]}

Piantedosi, Francovito ^{[18
]}

Calabro, Luana ^{[19
]}

Cappuzzo, Federico ^{[1
]}

机构：

[1] AUSL Romagna, Dept Oncol & Hematol, Ravenna, Italy

[2] Fdn Ric Traslazionale, Rome, Italy

[3] Policlin Umberto 1, Oncol Med B, Rome, Italy

[4] Santa Maria della Misericordia Hosp, Med Oncol, Perugia, Italy

[5] IRCCS Ca Granda Osped Maggiore Policlin, Div Med Oncol, Milan, Italy

[6] Ist Sci Romagnolo Studio & Cura Tumori, Meldola, Italy

[7] European Inst Oncol, Div Thorac Oncol, IEO, IRCCS, Milan, Italy

[8] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[9] St Orsola Marcello Malpighi Hosp, Oncol Med, Bologna, Italy

[10] IRCCS Ist Tumori Giovanni Paolo II, Oncol Med Torac, Bari, Italy

[11] IRCCS, Regina Elena Natl Canc Inst, Rome, Italy

[12] AOU Policlin Vittorio Emanuele, Catania, Italy

[13] Azienda Usl Toscana Nord Ovest, UO Oncol Med, Livorno, Italy

[14] Univ Hosp, Med Oncol Unit, Parma, Italy

[15] Azienda Osped San Camillo Forlanini, UOSD Pneumol Oncol, Rome, Italy

[16] Humanitas Canc Ctr, Milan, Italy

[17] Osped San Gerardo, Oncol Unit, ASST, Monza, Italy

[18] AO Colli Monaldi Cotugno CTO, UOSD DH Pneumoncol, Naples, Italy

[19] Univ Hosp Siena, Ctr Immunooncol, Med Oncol & Immunotherapy, Siena, Italy

来源：

JOURNAL FOR IMMUNOTHERAPY OF CANCER | 2019年 / 7卷 / 01期

关键词：

Bone metastases; Nivolumab; Immunotherapy; PD-L1; Non-small-cell lung cancer; OPEN-LABEL; NIVOLUMAB; DOCETAXEL; PEMBROLIZUMAB; ATEZOLIZUMAB; CHEMOTHERAPY; COMBINATION; SURVIVAL; EFFICACY; PHASE-3;

D O I：

10.1186/s40425-019-0793-8

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background Bone metastases (BoM) are a negative prognostic factor in non-small-cell lung cancer (NSCLC). Beyond its supportive role, bone is a hematopoietic organ actively regulating immune system. We hypothesized that BoM may influence sensitivity to immunotherapy. Methods Pretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM. Results Cohort A accounted for 1588 patients with non-squamous NSCLC, including 626 (39%) with (BoM+) and 962 (61%) without BoM (BoM-). Cohort B accounted for 371 patients with squamous histology including 120 BoM+ (32%) and 251 (68%) BoM- cases. BoM+ had lower overall response rate (ORR; Cohort A: 12% versus 23%, p < 0.0001; Cohort B: 13% versus 22%, p = 0.04), shorter progression free survival (PFS; Cohort A: 3.0 versus 4.0 months, p < 0.0001; Cohort B: 2.7 versus 5.2 months, p < 0.0001) and overall survival (OS; Cohort A: 7.4 versus 15.3 months, p < 0.0001; Cohort B: 5.0 versus 10.9 months, p < 0.0001). Moreover, BoM negatively affected outcome irrespective of performance status (PS; OS in both cohorts: p < 0.0001) and liver metastases (OS cohort A: p < 0.0001; OS Cohort B: p = 0.48). At multivariate analysis, BoM independently associated with higher risk of death (cohort A: HR 1.50; cohort B: HR 1.78). Conclusions BoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

引用

页数：9

共 30 条

[1] Prognostic significance of sites of extrathoracic metastasis in patients with non-small cell lung cancer [J].

Bates, James E. ;

Milano, Michael T. .

JOURNAL OF THORACIC DISEASE, 2017, 9 (07) :1903-1910

[2] Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer [J].

Borghaei, H. ;

Paz-Ares, L. ;

Horn, L. ;

Spigel, D. R. ;

Steins, M. ;

Ready, N. E. ;

Chow, L. Q. ;

Vokes, E. E. ;

Felip, E. ;

Holgado, E. ;

Barlesi, F. ;

Kohlhaeufl, M. ;

Arrieta, O. ;

Burgio, M. A. ;

Fayette, J. ;

Lena, H. ;

Poddubskaya, E. ;

Gerber, D. E. ;

Gettinger, S. N. ;

Rudin, C. M. ;

Rizvi, N. ;

Crino, L. ;

Blumenschein, G. R. ;

Antonia, S. J. ;

Dorange, C. ;

Harbison, C. T. ;

Finckenstein, F. Graf ;

Brahmer, J. R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (17) :1627-1639

[3]

Borghaei H, NIVOLUMAB NIVO PLATI

[4] A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab [J].

Botticelli, Andrea ;

Salati, Massimiliano ;

Di Pietro, Francesca Romana ;

Strigari, Lidia ;

Cerbelli, Bruna ;

Zizzari, Ilaria Grazia ;

Giusti, Raffaele ;

Mazzotta, Marco ;

Mazzuca, Federica ;

Roberto, Michela ;

Vici, Patrizia ;

Pizzuti, Laura ;

Nuti, Marianna ;

Marchetti, Paolo .

JOURNAL OF TRANSLATIONAL MEDICINE, 2019, 17 (1)

[5] Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer [J].

Brahmer, Julie ;

Reckamp, Karen L. ;

Baas, Paul ;

Crino, Lucio ;

Eberhardt, Wilfried E. E. ;

Poddubskaya, Elena ;

Antonia, Scott ;

Pluzanski, Adam ;

Vokes, Everett E. ;

Holgado, Esther ;

Waterhouse, David ;

Ready, Neal ;

Gainor, Justin ;

Aren Frontera, Osvaldo ;

Havel, Libor ;

Steins, Martin ;

Garassino, Marina C. ;

Aerts, Joachim G. ;

Domine, Manuel ;

Paz-Ares, Luis ;

Reck, Martin ;

Baudelet, Christine ;

Harbison, Christopher T. ;

Lestini, Brian ;

Spigel, David R. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (02) :123-135

[6] Digital quantum simulators in a scalable architecture of hybrid spin-photon qubits [J].

Chiesa, Alessandro ;

Santini, Paolo ;

Gerace, Dario ;

Raftery, James ;

Houck, Andrew A. ;

Carretta, Stefano .

SCIENTIFIC REPORTS, 2015, 5

[7] New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].

Eisenhauer, E. A. ;

Therasse, P. ;

Bogaerts, J. ;

Schwartz, L. H. ;

Sargent, D. ;

Ford, R. ;

Dancey, J. ;

Arbuck, S. ;

Gwyther, S. ;

Mooney, M. ;

Rubinstein, L. ;

Shankar, L. ;

Dodd, L. ;

Kaplan, R. ;

Lacombe, D. ;

Verweij, J. .

EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247

[8]

Gandhi L, 2018, NEW ENGL J MED, V379

[9] Italian Nivolumab Expanded Access Program in Nonsquamous Non-Small Cell Lung Cancer Patients: Results in Never-Smokers and EGFR-Mutant Patients [J].

Garassino, Marina Chiara ;

Gelibter, Alain Jonathan ;

Grossi, Francesco ;

Chiari, Rita ;

Parra, Hector Soto ;

Cascinu, Stefano ;

Cognetti, Francesco ;

Turci, Daniele ;

Blasi, Livio ;

Bengala, Carmelo ;

Mini, Enrico ;

Baldini, Editta ;

Quadrini, Silvia ;

Ceresoli, Giovanni Luca ;

Antonelli, Paola ;

Vasile, Enrico ;

Pinto, Carmine ;

Fasola, Gianpiero ;

Galetta, Domenico ;

Macerelli, Marianna ;

Giannarelli, Diana ;

Lo Russo, Giuseppe ;

de Marinis, Filippo .

JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (08) :1146-1155

[10] Intracerebral efficacy and tolerance of nivolumab in non small-cell lung cancer patients with brain metastases [J].

Gauvain, Clement ;

Vauleon, Enora ;

Chouaid, Christos ;

Lerhun, Emilie ;

Jabot, Laurence ;

Scherpereel, Arnaud ;

Vinas, Florent ;

Cortot, Alexis Benjamin ;

Monnet, Isabelle .

LUNG CANCER, 2018, 116 :62-66

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