380P - Assessing interstitial lung disease (ILD) risk in metastatic breast cancer (MBC): A comprehensive meta and network analysis of antibody-drug conjugates (ADCs) compared to available treatment options beyond first-line (1L)

Background

ADCs are gaining momentum as crucial treatment options in all MBC subtypes, with ILD emerging as a significant adverse event. Aim of this meta-analysis (MA) was to assess the risk of ADC-induced ILD compared to other available treatment options beyond 1L in patients (pts) with MBC.

Methods

A generalized linear mixed model was used for a random effects meta-analysis of logit transformed single proportions to calculate a pooled proportion of ILD. Subgroup analyses were conducted based on molecular subtype and treatment type. We also conducted a network MA (NMA) ranking treatments according to the surface under the cumulative ranking curve (SUCRA).

Results

Thirty-eight studies were identified, 12 in HER2-positive (HER2+) and 26 in HER2-negative (HER2-) MBC beyond 1L. ILD incidence was reported in 11 trials, yielding an overall ILD risk of 0.96% (95% CI: 0.38-2.4). The trials included BOLERO-3, DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, TULIP, BOLERO-2, SOLAR-1, TROPION-Breast01, TROPiCS-02 and EMBRACE. Among the 6,121 analyzed pts, 214 ILD events were reported. Pts with HER2+ MBC had a higher ILD risk (3.42%, 95% CI: 1.33-8.47) compared to those with HER2- MBC (p-value 0.003). Furthermore, a greater ILD risk was observed in pts treated with ADCs such as Trastuzumab-emtansine (T-DM1), Trastuzumab-deruxtecan (T-DXd), Trastuzumab-duocarmazine (T-Duo), Sacituzumab govitecan (SG), and Datopotamab-deruxtecan (Dato-DXd) compared to endocrine therapy (ET), chemotherapy (CT) and target therapy [including TKIs like lapatinib/neratinib/tucatinib and PARP inhibitors (PARPi)] (5.55% incidence in ADCs group vs 0.39% in non-ADC group, 95% CI: 2.45-12.09; p-value <0.0001). NMA showed that the worst-ranked ADC was T-DXd (SUCRA 0.2%), while the best-ranked treatment was CT (SUCRA 85%).

Conclusions

Pts treated with ADCs demonstrated a higher risk of ILD compared to those receiving ET, TKIs, PARPi, and CT, including regimens containing everolimus. These data may inform treatment and monitoring decision making, especially for pts with respiratory risk factors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Centro di Riferimento Oncologico di Aviano (CRO), IRCCS.

Funding

Italian Ministry of Health - Ricerca Corrente.

Disclosure

S. Spazzapan: Financial Interests, Personal, Other, speaker, travel grants, research grants: AstraZeneca, Daichii Sankyo, MSD, Novartis, Pfizer, Seagen, Mundipharma. L. Gerratana: Financial Interests, Personal, Advisory Board: AstraZeneca, Daichii Sankyo, Eli Lilly, GSK, Incyte, Novartis, Pfizer, Merck, Sharp & Dohme, Menarini Stemline, Abbvie; Financial Interests, Institutional, Research Funding: Menarini Silicon Biosystems; Financial Interests, Personal, Other, Travel expenses: Menarini Stemline. F. Puglisi: Financial Interests, Personal, Other, speaker, travel grants, research grants: Amgen, AstraZeneca, Daichii Sankyo, Celgene, Eisai, Eli Lilly, Exact Sciences, Gilead, Ipsen, Italfarmaco, Menarini, MSD, Novartis, Pierre Fabre, Pfizer, Roche, Seagen, Takeda, Viatris; Financial Interests, Institutional, Research Funding: AstraZeneca, Eisai, Roche. All other authors have declared no conflicts of interest.