According to a prospective clinical trial, the use of cell-free DNA (cfDNA)-guided adaptive treatment led to a median progression-free survival (PFS) that was comparable to historical controls for patients with advanced or metastatic PD-L1–positive non-small cell lung cancer (NSCLC).

These data will first be presented by Julia Rotow, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, at the 2025 American Society for Clinical Oncology (ASCO) in Chicago, Illinois.

As Dr Rotow et al wrote, “There is clinical uncertainty as to which patients with advanced/metastatic NSCLC require first-line treatment with chemoimmunotherapy versus treatment with immune checkpoint inhibitor monotherapy.” PD-L1 expression can predict response to immunotherapy but “it is an imperfect biomarker.” The use of cfDNA clearance predicts for benefit to immunotherapy for patients with metastatic NSCLC.

In this trial, 40 patients with advanced or metastatic PD-L1–positive NSCLC (PD-L1 low [TPS 1 to 49%], n = 15) received 2 cycles of pembrolizumab before being assessed for plasma and radiographic response. Those patients who showed radiographic response or radiographic stable disease with plasma response continued to receive monotherapy. Those patients with stable disease without plasma response received carboplatin doublet (paclitaxel for squamous;  pemetrexed for nonsquamous) plus pembrolizumab. Patients with radiographic progression ended study treatment.

Of the 40 patients, 36 completed a C2D2 plasma response assessment. Of those 36, 58.3% showed a plasma response to immune checkpoint inhibitor monotherapy (PD-L1 low, 57.1%; PD-L1 high [TPS ≥ 50%], 59.1%). There were 52.8% of patients who continued on pembrolizumab monotherapy following the initial 2 cycles (partial response, n = 7; stable disease with plasma response, n = 12), while 19.4% achieved radiographic stable disease with plasma non-response and were intensified to chemoimmunotherapy (pemetrexed, n = 6; paclitaxel, n = 1). The remaining 27.8% went off study due to progressive disease (n = 4), death (n = 1), adverse event (n = 3), or patient/physician decision (n = 2). Twenty percent of PD-L1 low patients and 16% of PD-L1 high patients received treatment intensification to chemoimmunotherapy.

The objective response rate to the adaptive treatment strategy overall was 50% with a median PFS of 11 months and a median overall survival (OS) of 14.9 months. The median PFS was higher among patients with a plasma response (16.4 months) vs those without (4.8 months; hazard ratio, 0.34). Fewer patients received the platinum doublet chemotherapy than was predicted by PD-L1 status alone.

Dr Rotow et al noted, “Further study within a randomized prospective trial design is needed to validate this treatment strategy.”

Source:

Rotow J, Heavey G, Nishino M, et al. Plasma-guided adaptive first-line chemoimmunotherapy for non-small cell lung cancer (NSCLC). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 8515.