Antibody-drug conjugates and pneumonitis risk in breast cancer patients.

e23312 Background: Antibody-drug conjugates (ADCs) are a novel treatment for breast cancer. Concerns have been raised about their potential to increase the risk of pneumonitis, particularly in patients who have received prior radiation therapy. This study aimed to investigate the incidence of pneumonitis in breast cancer patients treated with ADCs, with and without prior radiation therapy. Methods: This study reports on a retrospective Real-World Data (RWD) analysis of breast cancer patients treated with or without ADCs and stratified by prior radiation exposure from the TriNetX claims database. A total of 236,510 patients were included in this analysis. Of these, 9,930 patients had received radiation therapy, while 226,580 had not. The incidence of pneumonitis between patients exposed to ADCs and those not exposed, both with and without a history of radiation were compared. Results: In the radiation group (n = 9,930), 1,040 patients were exposed to ADCs and 8,890 were not. The incidence of pneumonitis was 0.96% (10/1,040) in the ADC-exposed group compared to 0.22% (20/8,890) in the non-exposed group. This difference was statistically significant (p < 0.001, chi-square test). In the no-radiation group (n = 226,580), 20,590 patients were exposed to ADCs, and 206,060 were not. The incidence of pneumonitis was 0.73% (150/20,590) in the ADC-exposed group compared to 0.25% (520/206,060) in the non-exposed group. This difference was also statistically significant (p < 0.001, chi-square test). The relative risk (RR) of pneumonitis with ADC exposure was 4.36 (95% CI: 2.06-9.24) in the radiation group and 2.92 (95% CI: 2.44-3.49) in the no-radiation group. When comparing ADC-exposed patients with and without prior radiation, the incidence of pneumonitis was not significantly different (0.96% vs 0.73%, p = 0.37). Conclusions: These findings support the hypothesis that breast cancer patients who receive ADCs have a higher incidence of pneumonitis, both with and without prior radiation. The risk appears to be more pronounced in patients who have received radiation therapy, although the difference was not statistically significant. The absolute risk of pneumonitis remains low ( < 1%) in all groups, but the relative increase in risk with ADC exposure is substantial. This suggests that while ADCs offer important therapeutic benefits, they may also carry an increased risk of pulmonary complications. While the retrospective nature of this study may introduce selection bias and potential confounds such as age, comorbidities, or specific ADC types clinicians should be aware of the potential for increased risk of pneumonitis in breast cancer patients treated with ADCs.