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

Authors
  • Landi, Lorenza1
  • D’Incà, Federica2
  • Gelibter, Alain3
  • Chiari, Rita4
  • Grossi, Francesco5
  • Delmonte, Angelo6
  • Passaro, Antonio7
  • Signorelli, Diego8
  • Gelsomino, Francesco9
  • Galetta, Domenico10
  • Giannarelli, Diana11
  • Soto Parra, Hector12
  • Minuti, Gabriele13
  • Tiseo, Marcello14
  • Migliorino, Maria Rita15
  • Cognetti, Francesco11
  • Toschi, Luca16
  • Bidoli, Paolo17
  • Piantedosi, Francovito18
  • Calabro’, Luana19
  • And 1 more
  • 1 Department of Oncology and Hematology, AUSL Romagna, Ravenna, Italy , Ravenna (Italy)
  • 2 Fondazione Ricerca Traslazionale, Rome, Italy , Rome (Italy)
  • 3 Oncologia Medica B, Policlinico Umberto I, Rome, Italy , Rome (Italy)
  • 4 Santa Maria della Misericordia Hospital, Perugia, Italy , Perugia (Italy)
  • 5 IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy , Milan (Italy)
  • 6 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy , Meldola (Italy)
  • 7 IEO, European Institute of Oncology IRCCS, Milan, Italy , Milan (Italy)
  • 8 Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy , Milan (Italy)
  • 9 Oncologia Medica, Policlinico S. Orsola – Malpighi, Bologna, Italy , Bologna (Italy)
  • 10 IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy , Bari (Italy)
  • 11 IRCCS - Regina Elena National Cancer Institute, Rome, Italy , Rome (Italy)
  • 12 AOU Policlinico Vittorio Emanuele, Catania, Italy , Catania (Italy)
  • 13 UO Oncologia Medica, Azienda Usl Toscana Nord Ovest, Livorno, Italy , Livorno (Italy)
  • 14 University Hospital, Parma, Italy , Parma (Italy)
  • 15 UOSD Pneumologia Oncologica, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy , Rome (Italy)
  • 16 Humanitas Cancer Center, Rozzano, Milan, Italy , Milan (Italy)
  • 17 Oncology Unit, ASST, Ospedale S. Gerardo, Monza, Italy , Monza (Italy)
  • 18 U.O.S.D. DH Pneumoncologico, A.O. Dei Colli Monaldi - Cotugno-CTO, Naples, Italy , Naples (Italy)
  • 19 University Hospital of Siena, Siena, Italy , Siena (Italy)
Type
Published Article
Journal
Journal for ImmunoTherapy of Cancer
Publisher
Springer (Biomed Central Ltd.)
Publication Date
Nov 21, 2019
Volume
7
Issue
1
Identifiers
DOI: 10.1186/s40425-019-0793-8
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundBone 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.MethodsPretreated non-squamous (cohort A) and squamous (cohort B) NSCLCs included in the Italian Expanded Access Program were evaluated for nivolumab efficacy according to BoM.ResultsCohort 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).ConclusionsBoM impairs immunotherapy efficacy. Accurate bone staging should be included in clinical trials with immunotherapy.

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