Bone metastases and immunotherapy in patients with advanced non-small-cell lung cancer. Issue 1 (21st November 2019)

• Record Type: Journal Article
• Authors: Landi, Lorenza; D'Incà, Federica; Gelibter, Alain; Chiari, Rita; Grossi, Francesco; Delmonte, Angelo; Passaro, Antonio; Signorelli, Diego; Gelsomino, Francesco; Galetta, Domenico; Giannarelli, Diana; Soto Parra, Hector; Minuti, Gabriele; Tiseo, Marcello; Migliorino, Maria Rita; Cognetti, Francesco; Toschi, Luca; Bidoli, Paolo; Piantedosi, Francovito; Calabro', Luana; Cappuzzo, Federico
• Is Part Of: Journal for immunotherapy of cancer. Volume 7:Issue 1(2019)
• Publication Date: 2019-11-21
• Subjects: Bone metastases -- Nivolumab -- Immunotherapy -- PD-L1 -- Non-small-cell lung cancer; Cancer -- Immunotherapy -- Periodicals; Cancer -- Immunological aspects -- Periodicals; Tumors -- Immunological aspects -- Periodicals; Immunotherapy -- Periodicals; 616.99406105
• DOI: 10.1186/s40425-019-0793-8
• Languages: English
• ISSNs: 2051-1426

Abstract

Abstract : 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.