Validation of Real-World Pathologic Complete Response in Early Stage Triple Negative Breast Cancer
Author(s)
Carole Berini, PhD1, Jessica K. Paulus, ScD1, Malcolm Charles, M.S.1, Zhaohui Su, PhD1, Paul Conkling, M.D.1, Nina Balanchivadze, MD, FACP2, Jagadeswara Rao Earla, MBA, PharmD, PhD3, Amin Haiderali, MBA, MPH3, Kaushal Desai, PhD3.
1Ontada, Boston, MA, USA, 2The US Oncology Network, Norfolk, VA, USA, 3Merck, Rahway, NJ, USA.
1Ontada, Boston, MA, USA, 2The US Oncology Network, Norfolk, VA, USA, 3Merck, Rahway, NJ, USA.
Presentation Documents
OBJECTIVES: Reliable real-world clinical outcome measures are needed to support health technology assessment (HTA), provider and regulatory decision-making in early-stage triple negative breast cancer (eTNBC). Population-based studies have confirmed the potential of real-world pathologic complete response (rwpCR) as an effectiveness outcome. Nonetheless, there is a lack of evidence on validation of rwpCR compared to clinical trial pathological complete response (pCR) estimates. This retrospective observational study examined the concordance between rwpCR and KEYNOTE-522 trial ‘chemotherapy only’ arm pCR estimates.
METHODS: Electronic health records from The US Oncology Network were used to identify patients with stage II-III TNBC who initiated neoadjuvant chemotherapy between 1/1/20 and 3/31/22. Patients were followed through 07/18/23. Patients treated with immunotherapy at any time were excluded. Trial eligibility criteria were applied to identify a real-world cohort. Differences in available demographic and clinical characteristics were adjusted through the Matching-Adjusted Indirect Comparison method. rwpCR and KEYNOTE-522 comparator arm pCR were compared using generalized linear models.
RESULTS: Real-world patients (n=199) were older when compared with KEYNOTE-522 trial participants (median age 59 vs 48 years), with more advanced disease (61% vs 25% stage III), and more often ECOG>0 (40% vs 13). In unadjusted analyses, real-world patients were 15% less likely to achieve pCR when compared to patients in the comparator arm, though this difference was not statistically significant (RR: 0.85, 95% CI: 0.69, 1.05). After adjustment for age, race, ethnicity, clinical stage at diagnosis, and ECOG, there was a greater concordance between the real-world cohort rwpCR and the KEYNOTE-522 comparator arm pCR (RR: 0.92, 95% CI: 0.75 - 1.13).
CONCLUSIONS: With the application of real-world definitions to match key study design elements and real-world population with the trial, and leveraging curated data, real-world pathologic complete response is concordant with clinical trial estimates in eTNBC. These results increase confidence in the validity of real-world outcomes for eTNBC.
METHODS: Electronic health records from The US Oncology Network were used to identify patients with stage II-III TNBC who initiated neoadjuvant chemotherapy between 1/1/20 and 3/31/22. Patients were followed through 07/18/23. Patients treated with immunotherapy at any time were excluded. Trial eligibility criteria were applied to identify a real-world cohort. Differences in available demographic and clinical characteristics were adjusted through the Matching-Adjusted Indirect Comparison method. rwpCR and KEYNOTE-522 comparator arm pCR were compared using generalized linear models.
RESULTS: Real-world patients (n=199) were older when compared with KEYNOTE-522 trial participants (median age 59 vs 48 years), with more advanced disease (61% vs 25% stage III), and more often ECOG>0 (40% vs 13). In unadjusted analyses, real-world patients were 15% less likely to achieve pCR when compared to patients in the comparator arm, though this difference was not statistically significant (RR: 0.85, 95% CI: 0.69, 1.05). After adjustment for age, race, ethnicity, clinical stage at diagnosis, and ECOG, there was a greater concordance between the real-world cohort rwpCR and the KEYNOTE-522 comparator arm pCR (RR: 0.92, 95% CI: 0.75 - 1.13).
CONCLUSIONS: With the application of real-world definitions to match key study design elements and real-world population with the trial, and leveraging curated data, real-world pathologic complete response is concordant with clinical trial estimates in eTNBC. These results increase confidence in the validity of real-world outcomes for eTNBC.
Conference/Value in Health Info
2025-05, ISPOR 2025, Montréal, Quebec, CA
Value in Health, Volume 28, Issue S1
Code
RWD110
Topic
Real World Data & Information Systems
Topic Subcategory
Reproducibility & Replicability
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Oncology