Study Investigates How ctDNA May Help Personalize Immunotherapy Treatment for Inoperable NSCLC

Circulating tumor DNA (ctDNA) may help guide oncologists in determining which patients with inoperable stage III non-small cell lung cancer (NSCLC) need to receive immunotherapy for a longer amount of time, according to study findings published in the Journal of Thoracic Oncology.

The current standard of care for this patient population consists of chemoradiotherapy (CRT) followed by 1 year of checkpoint inhibitor (CPI) therapy.

To determine the optimal duration of consolidation CPI, the team of researchers led by Soyeong Jun, PhD, of the Stanford Cancer Institute, reviewed the relationship between minimal residual disease (MRD) determined by ctDNA and clinical outcomes in patients with NSCLC. They used plasma samples from patients (n=105) enrolled in the phase II BTCRC LUN 16-081 trial (NCT03285321). The samples were collected after completion of CRT, prior to day 1 of the second cycle (C2D1) of CPI, and at the end of up to 6 months of treatment.

The researchers used ctDNA levels from each time point and evaluated those with clinical outcomes in patients with unresectable locally advanced disease.

Study findings showed that the detection of ctDNA predicted significantly inferior progression-free survival (PFS) after each of the 3 periods. Following the completion of CRT, the 24-month PFS was 29% in patients where ctDNA MRD was detected compared with 65% of patients without it present. Furthermore, prior to C2D1 of CPI PFS was 0% versus 72% at 24 months, respectively. The 24-month PFS rate was 15% versus 67% at the end of CPI, respectively.

Improved survival outcomes were seen in patients with NSCLC who had decreasing or undetectable ctDNA levels after 1 cycle of CPI compared with patients with increasing ctDNA levels (24-month PFS 72% vs 0%).

All patients with increasing ctDNA levels at C2D1 saw progression of disease within 12 months of starting CPI.

“Detection of ctDNA before, during, or after 6 months of consolidation CPI is strongly associated with inferior outcomes,” the researchers said. The researchers added that this ctDNA MRD analysis may allow for a more personalized approach to the duration of consolidation immunotherapy treatment.

Source: Journal of Thoracic Oncology