Top Line: Are there biomarker predictors of treatment outcome in cervical cancer?
The Study: In KEYNOTE-A18, adding pembrolizumab to chemoradiation and brachytherapy for locally advanced cervical cancer improved progression free survival. However, molecular biomarkers currently don’t play a big role in guiding treatment for locally advanced cervical cancer. BIOEMBRACE-I (a companion study of the EMBRACE) investigated the associations between p16 expression, L1CAM (a marker of the epithelial mesenchymal transformation pathway), and PD-L1 and treatment outcomes in 264 patients treated with chemoradiation and brachytherapy. P16 was positive in 86.6%, L1CAM expression was >10% in 17.8%, and PD-L1 was >1% in 20.1%. L1CAM expression was more common in adenocarcinomas (38.3% v 13.3%) while p16 expression was less common (78.3% v 88.6%). Of note, p16 positive tumors are more likely to co-express L1CAM. PD-L1 was the only factor significantly associated with local control, but not in the way you’d expect. Local control was lower in those with PD-L1 >1% (82% v 94%). Importantly, this finding seemed to be driven by events in PD-L1 positive patients whose HR-CTV D90 was <85 Gy. In patients who received a HR-CTV D90 >85 Gy, local control was excellent regardless of biomarker expression. Higher L1CAM expression (>50%) was associated with significantly worse nodal control (40% v 88%). None of the biomarkers were associated with distant control.
TBL: BIOEMBRACE-I lays the groundwork for investigating differential responses to standard therapy in different biological subtypes of locally advanced cervical cancer. | Chopra, Int J Radiat Oncol Biol Phys 2024
The Study: In KEYNOTE-A18, adding pembrolizumab to chemoradiation and brachytherapy for locally advanced cervical cancer improved progression free survival. However, molecular biomarkers currently don’t play a big role in guiding treatment for locally advanced cervical cancer. BIOEMBRACE-I (a companion study of the EMBRACE) investigated the associations between p16 expression, L1CAM (a marker of the epithelial mesenchymal transformation pathway), and PD-L1 and treatment outcomes in 264 patients treated with chemoradiation and brachytherapy. P16 was positive in 86.6%, L1CAM expression was >10% in 17.8%, and PD-L1 was >1% in 20.1%. L1CAM expression was more common in adenocarcinomas (38.3% v 13.3%) while p16 expression was less common (78.3% v 88.6%). Of note, p16 positive tumors are more likely to co-express L1CAM. PD-L1 was the only factor significantly associated with local control, but not in the way you’d expect. Local control was lower in those with PD-L1 >1% (82% v 94%). Importantly, this finding seemed to be driven by events in PD-L1 positive patients whose HR-CTV D90 was <85 Gy. In patients who received a HR-CTV D90 >85 Gy, local control was excellent regardless of biomarker expression. Higher L1CAM expression (>50%) was associated with significantly worse nodal control (40% v 88%). None of the biomarkers were associated with distant control.
TBL: BIOEMBRACE-I lays the groundwork for investigating differential responses to standard therapy in different biological subtypes of locally advanced cervical cancer. | Chopra, Int J Radiat Oncol Biol Phys 2024