Abstract 1035P
Background
Bone metastases are frequent in patients with NSCLC and often associated with a worse prognosis. Denosumab blocks RANK-Ligand binding to its receptor and inhibits osteoclastogenesis. Retrospective studies suggested a synergistic interaction between denosumab and immune-checkpoint inhibitors.
Methods
We conducted a phase II multicenter, single-arm trial, evaluating the efficacy of a second-line treatment combining nivolumab and denosumab, after first-line platinum-based chemotherapy, in stage IV, Performans status 0/1 NSCLC patients, with bone metastases and without EGFR or Braf V600E mutations or ALK/ROS-1 translocation. Primary endpoint was objective response rate (ORR) in patients with PD-L1 <1% and ≥ 1%.
Results
Between November 8, 2018 and December 31, 2021, 82 patients were included. Median age 67 years (IQR, 61-73), male 79.3%, smoking status was active, former, non-smokers: 28.0%/ 65.9% / 6.1%; adenocarcinoma: 76.8%; tumoral PD-L1 expression negative / ≥1% in 47.6% / 52.4% of cases; 11 patients (13.4%) had a skeletal-related event (SRE) at inclusion, and the median number of bone metastasis sites was three (IQR, 2-4). At the cutoff date of March 31, 2022, median follow-up was 24.4 months (95CI%, 20.4 to 26.2), median number of infusions were five (IQR, 3-10) for nivolumab and three (IQR, 2-6) for denosumab. ORR was 10.3% (95CI%, 4.1 to 23.6) and 18.6% (95CI%, 9.7 to 32.6) for patients with PD-L1 negative and PD-L1 ≥ 1%, respectively, and 14.6% (95CI%, 8.6-23.9) in the overall population. Disease control rate was 42.7% (95CI%, 32.5-53). Median progression-free survival was 1.7 months (IQR, 1.5-5.3), and median overall survival was 8.3 months (95CI%, 5.3-12.9). Ten patients developed new SRE after a median of 2.1 months (IQR, 1.2-3.3). Grade ≥3 adverse events occurred in 20.4%. No treatment-related death was reported.
Conclusions
The nivolumab and denosumab association is an effective treatment option in the second-line setting of NSCLC with bone metastases. ORR observed is in line with pivotal phase III studies. No unexpected toxicity was observed. Supported by an unrestricted educational grant from Amgen.
Clinical trial identification
NCT03669523.
Editorial acknowledgement
Legal entity responsible for the study
Centre Hospitalier Annecy Genevois and French Lung Cancer Group (GFPC).
Funding
Amgen.
Disclosure
C. Decroisette: Financial Interests, Personal, Advisory Role: Roche, Takeda, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca, Amgen; Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi-Aventis, Janssen Cilag, Lilly, MSD, Novartis, Pfizer. C. Ricordel: Financial Interests, Personal, Advisory Board: BMS, Takeda, AstraZeneca; Financial Interests, Personal, Funding: AstraZeneca. L. Falchero: Financial Interests, Personal, Advisory Board: Roche, BMS, MSD, AstraZeneca, Pfizer; Financial Interests, Personal, Speaker’s Bureau: Menarini, Chiesi; Financial Interests, Personal, Invited Speaker: Amgen. O. Bylicki: Financial Interests, Personal, Expert Testimony: BMS, AstraZeneca, MSD, Roche; Non-Financial Interests, Institutional, Funding: AstraZeneca, MSD, Roche. M. Geier: Financial Interests, Institutional, Research Grant: BMS, Roche; Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, Sanofi, BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca. F. Guisier: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, MSD, Roche, Amgen; Financial Interests, Personal and Institutional, Invited Speaker: Takeda, Pfizer. P. Fournel: Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca, Sanofi, Amgen. J.B. Auliac: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Boehringer Ingelheim, BMS, Sanofi; Financial Interests, Personal, Invited Speaker: Takeda. C. Chouaid: Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, GSK, Roche, Sanofi, BMS, MSD, Lilly, Novartis, Pfizer, Takeda, Bayer, Amgen. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. All other authors have declared no conflicts of interest.