Antibody Drug Conjugates Show Promise in Biomarker, Prognostic Outcomes in Oncology Care

Two posters presented at ASCO 2024 evaluated the potential of antibody drug conjugates (ADCs) in oncology care, which allow for the use of stronger chemotherapy agents with less adverse effects.

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The first poster aimed to describe the use of ADC Treatment Response Scores (ADC-TRS), a tissue-based multivariate gene-expression test combining individual ADC target expression with proliferation and adhesion.¹

The study included adult patients with advanced solid tumors from an observational trial (NCT03061305) treated with an ADC with TRS results. One of the cohorts was limited to breast and bladder cancer. The second cohort, which included patients with pan-solid tumors, was analyzed separately.

The researchers evaluated whether treatment-matched ADC-TRS status was associated with overall survival (OS) after ADC treatment initiation, adjusting for age, indication, and years since tissue collection.

A total of 72 patients were included in the pan-solid tumor cohort, with 5 ADCs and 9 tumor types. The most frequently used ADC in this cohort was sacituzumab govitecan (SG) for breast cancer (43%). The other cohort included a total of 127 patients, with 3 ADCs and 2 tumor types. The most frequently used ADC in this cohort was enfortumab vedotin for bladder cancer (50%).

In both cohorts, ADC-TRS was significantly associated with OS (High vs Low; median OS, 22.8 vs 8.7 months; adjusted HR [aHR], 0.15; P = .005, and median OS, 15.3 vs 8.3 months; aHR, 0.58; P = .11), respectively. Additionally, a predictive biomarker effect was confirmed by a lack of ADC-TRS status association with OS from systemic chemotherapy start in indication-matched patients not treated with an ADC. Moreover, in a pan-tumor cohort (n = 15,108), 26.7% of patients were ADC-TRS High for at least 1 ADC approved outside of indications.

The second poster was a retrospective analysis that aimed to evaluate trends in the use of 2 ADCs trastuzumab deruxtecan (T-DXd) and SG among patients with HR+/HER2-negative (HER2–) MBC in a real-world setting.²

The researchers utilized a federal network of de-identified health data representing approximately 107 million patients. From this dataset, the researchers identified patients with HR+/HER2– MBC diagnosed between January 2004 and January 2024.

A total of 17,133 patients with HR+/HER2– MBC who received endocrine therapy and CDK4/6i were identified. Of these patients, 249 (1.45%) received SG, while 162 (0.94%) received T-DXd, and 32 (0.19%) received T-DXd+SG, respectively.

Five-year OS among patients who received T-DXd was higher than those who did not receive it (74.8% vs. 52.2%; HR, 0.44; 95% CI, 0.28-0.6; P = .0002), respectively. Similarly, 5-year OS was higher among patients who received SG compared with those who did not (73.4% vs 64.7%; HR, 0.62; 95% CI, 0.42-0.90; P = .012), respectively. Compared with patients who received T-DXd+SG and those who did not, 5-year OS was 77.4% vs 62.4% (HR, 0.55; 95% CI, 0.19-1.59; P = .26), respectively. Finally, 5-year OS was 68.1% and 74.5% among patients who received SG alone or T-DXd alone (HR, 1.31; 95% CI, 0.84-2.03; P = .22), respectively.

References

1. Thomas SP, Habel LA, Suga JM, et al. Evaluation of a predictive biomarker for antibody drug conjugates (ADCs). Poster presented at: ASCO; May 31-June 4, 2024; Chicago, IL. Accessed June 5, 2024. https://meetings.asco.org/abstracts-presentations/234107

2. Dawood SS, Hernandez G, Segovia A. Impact of use of antibody drug conjugates on the prognostic outcome of patients with HR+ve/HER2-ve MBC: Results from a real world dataset. Poster presented at: ASCO; May 31-June 4, 2024; Chicago, IL. Accessed June 5, 2024. https://meetings.asco.org/abstracts-presentations/233637