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Pretreatment levels of circulating tumor DNA (ctDNA) were significantly associated with survival in patients with non-small cell lung cancer (NSCLC) enrolled on a phase 2 trial.
On the other hand, PD-L1 expression and tumor mutational burden (TMB) were not associated with progression-free survival (PFS) or overall survival (OS) in these patients.
These results were presented at the IASLC 2021 World Conference on Lung Cancer (WCLC).
Researchers analyzed data from patients in the phase 2 NADIM trial (ClinicalTrials.gov Identifier: NCT04564157). The analysis included 46 patients with resectable, stage IIIA NSCLC.
Patients received neoadjuvant treatment with nivolumab, paclitaxel, and carboplatin (3 cycles), underwent surgery, and then received adjuvant treatment with nivolumab for 12 months.
The median follow-up was 38 months. Of the entire cohort, 35 patients had a biopsy sample available for next-generation sequencing, 29 had data for TMB assessment, and 28 had PD-L1 data.
PD-L1 and TMB Results
PD-L1 expression was not significantly associated with PFS at a cutoff of 1% (hazard ratio [HR], 0.78; 95% CI, 0.18-3.29) or 50% (HR, 1.10; 95% CI, 0.25-4.79), and it was not associated with OS at a cutoff of 1% (HR, 0.51; 95% CI, 0.07-3.68) or 50% (HR, 1.48; 95% CI, 0.17-13.02).
When the researchers assessed PD-L1 expression as a continuous variable, there was still no significant association with PFS or OS.
Similarly, when TMB was assessed as a continuous variable, there was no significant association with PFS (HR, 0.98; 95% CI, 0.91-1.06) or OS (HR, 0.99; 95% CI, 0.91-1.08). And there was no significant association with PFS or OS when the researchers used TMB cutoffs of 7, 10, or 16 mutations per megabase.
Among the 43 patients for whom pretreatment ctDNA data were available, 69.8% had evidence of baseline ctDNA. In these samples, the average number of mutations was 2 (range, 1-6).
A maximum allele frequency (MAF) less than 1% was significantly associated with PFS (HR, 0.26; 95% CI, 0.08-0.90; P =.033) and OS (HR, 0.05; 95% CI, 0.01-0.53; P =.012).
Similarly, a sum MAF less than 1% was significantly associated with PFS (HR, 0.22; 95% CI, 0.06-0.75; P =.016) and OS (HR, 0.04; 95% CI, 0.00-0.45; P =.008).
In fact, a sum MAF less than 1% was shown to better predict PFS (c-statistic, 0.68) and OS (c-statistic, 0.85) when compared with clinical response (c-statistic for PFS and OS, 0.61 and 0.68, respectively).
Disclosures: This research was supported by Bristol Myers Squibb. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Romero A, Provencio M, Nadal E, et al. Pre-treatment levels of ctDNA for long-term survival prediction in stage IIIA NSCLC treated with neoadjuvant chemo-immunotherapy. Presented at: IASLC 2021 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer; September 8-14, 2021; Abstract OA20.02.