Abstract 1327P
Background
BTA use in cancer pts with bone metastases (BM) can prevent skeletal related events. A subgroup analysis of aNSCLC pts showed an overall survival (OS) benefit with denosumab (DN) compared to zoledronic acid (ZA), while in the SPLENDOUR trial the addition of DN to 1st line chemotherapy did not improve OS. Currently, the impact of BTA in ICI treated BM aNSCLC remains unclear.
Methods
Data of ICI treated BM aNSCLC pts (3/2013-4/2021) in one institution were retrospectively collected. BTA therapy was defined as BTA-ICI concurrent treatment. HBTB was defined as presence of ≥3 BM. Median OS (mOS) and progression free survival (mPFS) were estimated with Kaplan-Meier, multivariate analysis was performed by Cox regression model. M follow up (mFU) was estimated by inverse Kaplan Meier.
Results
Of 151 pts, 68 (45%) received BTA. Clinical characteristics were balanced between the two groups. At a mFU of 35 months (m), BTA did not impact mOS [7.8 (CI 95% 4.5-11.1) vs 6.8 m (95% CI 4.0-9.6) p=0.61] or mPFS [1.5 (95% CI 1.1-1.8) vs 1.1 m (95% CI 0.9-1.2) p=0.47], even if a trend towards a better OS was observed in the DN group [mOS 15.2 (CI 95% 0.1-32.6) vs 6.8 m (CI 95% 4.0-9.6) p=0.09]. HBTB group included 78 pts: 21% received DN, 37% ZA, 42% no-BTA. In HBTB, BTA significantly improved both mOS [7.8 (95% CI 3.3-12.2) vs 3.5m (95% CI 2.9-4.1) p=0.01] and mPFS [1.4 (95% CI 1.0-1.8) vs 1.0 m (95% CI 0.8-1.2) p=0.002]. ZA did not impact mOS but prolonged mPFS [1.3 (95% CI 0.8-1.8) vs 1.0 m (95% CI 0.8-1.2) p=0.02], while DN improved mOS [15.2 (95% CI 0.1-4.8) vs 3.5 m (95% CI 2.9-4.1) p=0.002] and mPFS [1.5 (95% CI 0.5-2.5) vs 1.0 m (95% CI 0.8-1.2) p=0.004] compared to no-BTA. BTA associated benefit in OS [HR 0.56 (95% CI 0.33-0.98) p=0.04] and PFS [HR 0.46 (95% CI 0.26-0.79) p=0.005] was confirmed at multivariate analysis adjusting for PS, age, metastatic sites, dNLR; among BTA DN was confirmed to improve both OS [HR 0.37 (95% CI 0.16-0.86) p=0.02] and PFS [HR 0.41 (95% CI 0.19-0.89) p=0.02].
Conclusions
In ICI treated BM aNSCLC, BTA did not impact on survival. However, in HBTB pts BTA significantly improved both PFS and OS. Especially DN was associated with a survival benefit, suggesting a potential role of RANK ligand inhibition on ICI efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Fondazione IRCCS Istituto Nazionale dei Tumori.
Funding
Has not received any funding.
Disclosure
C. Proto: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: MSD. A. Prelaj: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: Roche. D. Signorelli: Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim. M.C.C. Garassino: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Eli Lilly, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda; Financial Interests, Institutional, Invited Speaker: Eli Lilly, MSD, Pfizer (MISP), AstraZeneca, MSD International GmbH, BMS, Boehringer Ingelheim Italia S.p.A, Celgene, Ignyta, Incyte, Inivata, MedImmune, Novartis, Pfizer, Roche, Takeda, Tiziana, Foundation Medicine; Other, Institutional, Funding: AIRC, AIFA, Italian Moh, Transcan. F.G.M. de Braud: Financial Interests, Personal and Institutional, Advisory Board, consultation, lectures: Amgen, AstraZeneca, Boehringer-Ingelheim, BMS, Eli Lilly, F. Hoffmann-La Roche, Ignyta, Merck Sharp & Dohme, Merck Serono, Novartis, Pfizer. G. Lo Russo: Financial Interests, Personal, Invited Speaker: Eli Lilly, BMS, Roche, Italfarmaco, Novartis, AstraZeneca. All other authors have declared no conflicts of interest.