Background
KEYNOTE-355 showed that adding pembrolizumab (P) to chemotherapy improved overall survival (OS) and progression-free survival (PFS) in advanced PDL-1+ TNBC. Conversely, Atezolizumab (A) did not exhibit an OS benefit in IMPASSION-130. Gaining insights into real-world outcomes beyond the confines of clinical trials is crucial.
Methods
This observational study at Roswell Park Comprehensive Cancer Center included pts with advanced PDL-1+ TNBC treated with P or A between January 2017-May 2023. We collected demographics, treatments, adverse events, and clinical outcomes data using (RECIST v1.1). SAS v9.4 was used for analyses at a significance level of 0.05.
Results
44 females with stage4, 23 received P and 21 A, median age 53 years, 68.2% White, 25.0% Black, and 34.1% obese (BMI≥30). 27.3% experienced grade 1 or 2 immune-related adverse events such as myocarditis, rash, hypo/hyperthyroidism, diabetes, and AKI. 75% pts received chemotherapy with ICI, 72.7% in first-line setting. Among 72.2% OS was 16.2 months(m) and PFS 4.4m. The overall response rate (ORR) was 29.1%, 8.3% achieving complete response and 20.8% partial response. ORR 22.2% for P and 33.3% A cohort. Obese pts who received first-line treatment had improved PFS compared to non-obese pts (11.5 vs 3.8m, p=0.031). Pts with brain metastases (Bm) had worse extracranial PFS compared to those without Bm (2.8 vs 5.2m, P=0.036), both trends persisted after adjusting for age.
Conclusions
Clinical outcomes in our study were inferior to KEYNOTE-355 where median PFS was 16.1m, OS 23m, ORR 52.7% for PDL-1+. This reflects a more heterogeneous population of pts treated in routine clinical practice who are less fit than pts on clinical trials. Our study showed improved outcomes among obese pts similar to data reported in other disease settings. These data highlight the need to understand the underlying mechanism associated with improved ICI outcomes among obese patients to deliver precision medicine.