Circulating Tumor DNA Presence Associated With Consolidation Immunotherapy Outcomes in NSCLC

For patients with inoperable stage III non-small cell lung cancer (NSCLC), measuring circulating tumor DNA (ctDNA) may help personalize the duration of consolidation immunotherapy, according to a recent analysis published in the Journal of Thoracic Oncology.

Soyeong Jun, PhD, of Stanford University, and a team of researchers from several national institutions reviewed the current standard of care for patients with NSCLC, which includes “chemoradiotherapy (CRT) followed by up to 1 year of checkpoint inhibitor (CPI) therapy with durvalumab.”

The goal of the analysis was to determine the “optimal duration of consolidation therapy” through emerging biomarkers like ctDNA, to assess patient response to consolidation CPI more accurately than through traditional radiologic methods.

In previous studies, the researchers found that the detection of minimum residual disease (MRD) after CRT “predicts the development of progressive disease in NSCLC with high sensitivity and specificity.” Due to these findings, the researchers hypothesized that by analyzing ctDNA, patient response to consolidation CPI could be determined sooner after treatment initiation, opening the door for future research to explore how ctDNA could be used to personalize consolidation CPI treatment on an individual basis.

To investigate whether ctDNA could be used to determine which patients require less than the standard year of consolidation CPI, the researchers collected patient plasma samples from the Big Ten Cancer Research Consortium (BTCRC) LUN 16-081 trial. The BTCRC LUN 16-081 trial “evaluated consolidation nivolumab or nivolumab plus ipilimumab after CRT in patients with unresectable stage III NSCLC.”

The samples originated from patients in the BTCRC LUN 16-081 trial who completed CRT before the first day of cycle two (C2D1), one month after the initiation of CPI therapy, and at the end of up to 6 months of treatment. Researchers aimed to evaluate the detection of ctDNA during and after those first six months.

The researchers stated that ctDNA MRD analysis was conducted through cancer personalized profiling by deep sequencing. ctDNA levels were measured at each timepoint and correlated with clinical outcomes.

According to the results, the presence of ctDNA “predicted significantly inferior” progression-free survival (PFS) at several timepoints throughout treatment. The first timepoint was completion of CRT (24 month PFS rate, 29% vs 65%, P=.0048), the second was before C2D1 of CPI (24-month PFS rate, 0% vs 72%, P<.0001), and the third was completion of CPI (24-month PFS rate, 15% vs 67%, P=.0011).

The study also found that patients with increasing ctDNA levels had worse outcomes than patients with decreasing or undetectable ctDNA levels after the first cycle of CPI (24-month PFS rate, 0% vs 72%, P<.0001). In all patients with increasing ctDNA levels at C2D1, disease progression occurred in less than one year after starting CPI therapy.

Investigators concluded that when ctDNA was detected before, during, or after CPI consolidation treatment, patients experienced inferior outcomes. They stated that “our findings suggest that analysis of ctDNA MRD may enable personalizing the duration of consolidation immunotherapy treatment.”

Source: Journal of Thoracic Oncology