Top Line: What is the intracranial activity of chemoimmunotherapy for untreated NSCLC brain metastases?
The Study: Systemic therapy won’t be replacing the role of radiation in the management of brain metastases anytime soon. However, there are scenarios where intracranially active systemic therapy regimens can be useful in delaying or deferring local therapy. In this single arm phase 2 trial (Atezo-Brain, GECP/1705), 40 patients with NSCLC and untreated brain metastases were treated with atezolizumab, carboplatin, and pemetrexed. Important inclusion criteria were that patients had to be either completely asymptomatic (45%) or asymptomatic on a maximum of 4mg dexamethasone daily (55%). Most patients (72.5%) were diagnosed with brain mets at the time of initial NSCLC diagnosis, and half (50%) had PD-L1 >1%. MRI was performed every 6 weeks. At 12 weeks, the progression-free survival rate was 62.2%. The complete response rate was 12.5%, partial response rate was 30%, and stable disease rate was 42.5%. Median PFS was 6.9 months. During the study, 60% required radiation for intracranial progression. Given the proven safety and efficacy of focal radiation for brain mets, a better question is how active are systemic therapy regimens in preventing further intracranial progression when combined with local therapy?
TBL: Atezolizumab, carboplatin, and pemetrexed have intracranial activity for asymptomatic NSCLC brain metastases. However, fewer than half have a measurable response and most progress within 6-7 months requiring radiation. | Nadal, J Clin Oncol 2023
The Study: Systemic therapy won’t be replacing the role of radiation in the management of brain metastases anytime soon. However, there are scenarios where intracranially active systemic therapy regimens can be useful in delaying or deferring local therapy. In this single arm phase 2 trial (Atezo-Brain, GECP/1705), 40 patients with NSCLC and untreated brain metastases were treated with atezolizumab, carboplatin, and pemetrexed. Important inclusion criteria were that patients had to be either completely asymptomatic (45%) or asymptomatic on a maximum of 4mg dexamethasone daily (55%). Most patients (72.5%) were diagnosed with brain mets at the time of initial NSCLC diagnosis, and half (50%) had PD-L1 >1%. MRI was performed every 6 weeks. At 12 weeks, the progression-free survival rate was 62.2%. The complete response rate was 12.5%, partial response rate was 30%, and stable disease rate was 42.5%. Median PFS was 6.9 months. During the study, 60% required radiation for intracranial progression. Given the proven safety and efficacy of focal radiation for brain mets, a better question is how active are systemic therapy regimens in preventing further intracranial progression when combined with local therapy?
TBL: Atezolizumab, carboplatin, and pemetrexed have intracranial activity for asymptomatic NSCLC brain metastases. However, fewer than half have a measurable response and most progress within 6-7 months requiring radiation. | Nadal, J Clin Oncol 2023