Phase II Efficacy and Safety of Pembrolizumab with Platinum Based Chemotherapy in Non-Small Cell Lung Cancer Patients with Untreated, Asymptomatic Brain Metastasis (PHOEBS).

[PURPOSE] Brain metastases are a serious complication in non-small cell lung cancer (NSCLC). However, data regarding efficacy of immune checkpoint inhibitors and chemotherapy combinations are limited. This phase II study aimed to evaluate the intracranial efficacy and safety of pembrolizumab and chemotherapy in treatment-naïve NSCLC patients with asymptomatic brain metastases.

[MATERIALS AND METHODS] This single-arm, phase II trial was conducted at Samsung Medical Center, Korea. Eligible patients had stage IV NSCLC with asymptomatic, untreated brain metastases and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) alterations. Patients received pembrolizumab with chemotherapy every 3 weeks for 4 cycles, followed by pembrolizumab with or without maintenance chemotherapy up to 35 cycles. The primary endpoint was intracranial objective response rate (icORR). Secondary endpoints included intracranial progression free survival (icPFS), intracranial duration of response (icDoR), objective response rate (ORR), progression free survival (PFS), overall survival, and safety.

[RESULTS] Between February 2021 and June 2024, a total of 13 patients were enrolled. Due to challenges in recruiting patients, enrollment was discontinued after the 13 patients. The icORR was 46.2% (95% CI, 19.2-74.8), with 6 patients achieving partial response. The median icPFS was 9.8 months (95% CI, 5.2-21.5), and median icDoR was 9.3 months (95% CI, 4.0-20.3). Median PFS and overall survival was 7.2 months (95% CI, 2.4-12.3) and 10.7 months (95% CI, 7.2-21.5), respectively. Most treatment-related adverse events were grade 1-2."

[CONCLUSION] Pembrolizumab combined with chemotherapy demonstrated encouraging intracranial activity and manageable safety profile in NSCLC patients with untreated, asymptomatic brain metastases.