Abstract
Original language | English |
---|---|
Journal | J. Immunother. Cancer |
Volume | 7 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2019 |
Keywords
- Bone metastases
- Immunotherapy
- Nivolumab
- Non-small-cell lung cancer
- PD-L1
- nivolumab
- adult
- advanced cancer
- aged
- anemia
- Article
- asthenia
- bone metastasis
- cancer immunotherapy
- cancer mortality
- cancer patient
- cohort analysis
- controlled clinical trial
- controlled study
- drug withdrawal
- dyspnea
- fatigue
- female
- high risk patient
- human
- human tissue
- liver metastasis
- major clinical study
- male
- multicenter study
- open study
- overall survival
- pneumonia
- premedication
- priority journal
- progression free survival
- prospective study
- single drug dose
- squamous cell lung carcinoma
- tissue section
- very elderly
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Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer : Journal for ImmunoTherapy of Cancer. / Landi, L.; D'Incà, F.; Gelibter, A. et al.
In: J. Immunother. Cancer, Vol. 7, No. 1, 2019.Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer
T2 - Journal for ImmunoTherapy of Cancer
AU - Landi, L.
AU - D'Incà, F.
AU - Gelibter, A.
AU - Chiari, R.
AU - Grossi, F.
AU - Delmonte, A.
AU - Passaro, A.
AU - Signorelli, D.
AU - Gelsomino, F.
AU - Galetta, D.
AU - Giannarelli, D.
AU - Soto Parra, H.
AU - Minuti, G.
AU - Tiseo, M.
AU - Migliorino, M.R.
AU - Cognetti, F.
AU - Toschi, L.
AU - Bidoli, P.
AU - Piantedosi, F.
AU - Calabro', L.
AU - Cappuzzo, F.
N1 - Cited By :1 Export Date: 27 February 2020 Correspondence Address: Cappuzzo, F.; Department of Oncology and Hematology, AUSL RomagnaItaly; email: f.cappuzzo@gmail.com Chemicals/CAS: nivolumab, 946414-94-4 References: Reck, M., Rodríguez-Abreu, D., Robinson, A.G., Hui, R., Csoszi, T., Fülöp, A., Pembrolizumab versus chemotherapy for PD-L1-positive non-small-cell lung Cancer (2016) N Engl J Med, 375, pp. 1823-1833. , 1:CAS:528:DC%2BC28XhvF2ks77I; Gandhi, L., Rodríguez-Abreu, D., Gadgeel, S., Esteban, E., Felip, E., De Angelis, F., Pembrolizumab plus chemotherapy in metastatic non-small-cell lung Cancer (2018) N Engl J Med.; Socinski, M.A., Jotte, R.M., Cappuzzo, F., Orlandi, F., Stroyakovskiy, D., Nogami, N., Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC (2018) N Engl J Med, 378, pp. 2288-2301. , 1:CAS:528:DC%2BC1cXhtFKkt77K; Herbst, R.S., Baas, P., Kim, D.-W., Felip, E., Pérez-Gracia, J.L., Han, J.-Y., Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): A randomised controlled trial (2016) Lancet., 387, pp. 1540-1550. , 1:CAS:528:DC%2BC2MXitVGrtLzI; Rittmeyer, A., Barlesi, F., Waterkamp, D., Park, K., Ciardiello, F., Von Pawel, J., Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): A phase 3, open-label, multicentre randomised controlled trial (2017) Lancet., 389, pp. 255-265; Borghaei, H., Paz-Ares, L., Horn, L., Spigel, D.R., Steins, M., Ready, N.E., Nivolumab versus Docetaxel in advanced non-squamous non-small cell lung Cancer (2015) N Engl J Med, 373, pp. 1627-1639. , 1:CAS:528:DC%2BC28XjsFyitL0%3D; Brahmer, J., Reckamp, K.L., Baas, P., Crinò, L., Eberhardt, W.E.E., Poddubskaya, E., Nivolumab versus Docetaxel in advanced squamous-cell non-small-cell lung Cancer (2015) N Engl J Med, 373, pp. 123-135. , 1:CAS:528:DC%2BC2MXht12qu7%2FJ; Planchard, D., Popat, S., Kerr, K., Novello, S., Smit, E.F., Faivre-Finn, C., Metastatic non-small cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up (2019) Ann Oncol; Borghaei, H., Hellmann, M.D., Paz-Ares, L.G., Nivolumab (Nivo) + Platinum-doublet Chemotherapy (Chemo) Vs Chemo As First-line (1L) Treatment (Tx) for Advanced Non-small Cell Lung Cancer (NSCLC) with <1% Tumor PD-L1 Expression: Results from CheckMate 227 [Abstract]; Botticelli, A., Salati, M., Di Pietro, F.R., Strigari, L., Cerbelli, B., Zizzari, I.G., A nomogram to predict survival in non-small cell lung cancer patients treated with nivolumab (2019) J Transl Med, 17, p. 99; Tamiya, M., Tamiya, A., Inoue, T., Kimura, M., Kunimasa, K., Nakahama, K., Metastatic site as a predictor of nivolumab efficacy in patients with advanced non-small cell lung cancer: A retrospective multicenter trial (2018) PLoS One, 13. , e0192227; Schmid, S., Diem, S., Li, Q., Krapf, M., Flatz, L., Leschka, S., Organ-specific response to nivolumab in patients with non-small cell lung cancer (NSCLC) (2018) Cancer Immunol Immunother, 67, pp. 1825-1832. , 1:CAS:528:DC%2BC1cXhs1ekur7I; Roodman, G.D., Mechanisms of bone metastasis (2004) N Engl J Med, 350, pp. 1655-1664. , 1:CAS:528:DC%2BD2cXjt1WksLY%3D; Kuchuk, M., Addison, C.L., Clemons, M., Kuchuk, I., Wheatley-Price, P., Incidence and consequences of bone metastases in lung cancer patients (2013) Journal of Bone Oncology, 2, pp. 22-29; Santini, D., Barni, S., Intagliata, S., Falcone, A., Ferraù, F., Galetta, D., Natural History of Non-Small-Cell Lung Cancer with Bone Metastases (2015) Sci Rep [Internet], 5. , https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687045/; Zhao, E., Xu, H., Wang, L., Kryczek, I., Wu, K., Hu, Y., Bone marrow and the control of immunity (2012) Cell Mol Immunol, 9, pp. 11-19. , 1:CAS:528:DC%2BC38Xjs1Gjuw%3D%3D; Garassino, M.C., Gelibter, A.J., Grossi, F., Chiari, R., Soto Parra, H., Cascinu, S., Italian Nivolumab expanded access program in nonsquamous non-small cell lung Cancer patients: Results in never-smokers and EGFR-mutant patients (2018) J Thorac Oncol, 13, pp. 1146-1155; Grossi, F., Crinò, L., Logroscino, A., Canova, S., Delmonte, A., Melotti, B., Use of nivolumab in elderly patients with advanced squamous non-small-cell lung cancer: Results from the Italian cohort of an expanded access programme (2018) Eur J Cancer, 100, pp. 126-134. , 1:CAS:528:DC%2BC1cXhtF2jsbzK; Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R., New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) (2009) Eur J Cancer, 45, pp. 228-247. , 1:STN:280:DC%2BD1M%2Fgs12rug%3D%3D; 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Gauvain, C., Vauléon, E., Chouaid, C., Lerhun, E., Jabot, L., Scherpereel, A., Intracerebral efficacy and tolerance of nivolumab in non-small-cell lung cancer patients with brain metastases (2018) Lung Cancer, 116, pp. 62-66; Melani, C., Sangaletti, S., Barazzetta, F.M., Werb, Z., Colombo, M.P., Amino-biphosphonate-mediated MMP-9 inhibition breaks the tumor-bone marrow axis responsible for myeloid-derived suppressor cell expansion and macrophage infiltration in tumor stroma (2007) Cancer Res, 67, pp. 11438-11446. , 1:CAS:528:DC%2BD2sXhtlyiu7rF; Hellmann, M.D., Paz-Ares, L., Bernabe Caro, R., Zurawski, B., Kim, S.-We., Carcereny Costa, E., Park, K., Ramalingam, S.S., Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer (2019) New England Journal of Medicine, 381 (21), pp. 2020-2031; Peters, S., Cappuzzo, F., Horn, L., Paz-Ares, L., Borghaei, H., Barlesi, F., OA03.05 Analysis of Early Survival in Patients with Advanced Non-Squamous NSCLC Treated with Nivolumab vs Docetaxel in CheckMate 057 (2017) Journal of Thoracic Oncology, 12, p. 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PY - 2019
Y1 - 2019
N2 - 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. © 2019 The Author(s).
AB - 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. © 2019 The Author(s).
KW - Bone metastases
KW - Immunotherapy
KW - Nivolumab
KW - Non-small-cell lung cancer
KW - PD-L1
KW - nivolumab
KW - adult
KW - advanced cancer
KW - aged
KW - anemia
KW - Article
KW - asthenia
KW - bone metastasis
KW - cancer immunotherapy
KW - cancer mortality
KW - cancer patient
KW - cohort analysis
KW - controlled clinical trial
KW - controlled study
KW - drug withdrawal
KW - dyspnea
KW - fatigue
KW - female
KW - high risk patient
KW - human
KW - human tissue
KW - liver metastasis
KW - major clinical study
KW - male
KW - multicenter study
KW - open study
KW - overall survival
KW - pneumonia
KW - premedication
KW - priority journal
KW - progression free survival
KW - prospective study
KW - single drug dose
KW - squamous cell lung carcinoma
KW - tissue section
KW - very elderly
U2 - 10.1186/s40425-019-0793-8
DO - 10.1186/s40425-019-0793-8
M3 - Article
VL - 7
JO - J. Immunother. Cancer
JF - J. Immunother. Cancer
SN - 2051-1426
IS - 1
ER -