Abstract Purpose: Perioperative chemoimmunotherapy is the standard of care for resectable, locally advanced non-small cell lung cancer (NSCLC). While pathological complete response (pCR) correlates with excellent survival outcomes, some patients without pCR still exhibit long-term survival. Here we evaluate the added value of minimal residual disease (MRD). Experimental Design: MRD was assessed in 60 patients from the NADIM II trial (NCT03838159) using Guardant Reveal assay. In NADIM II, NSCLC patients without EGFR or ALK alterations were randomized to receive neoadjuvant nivolumab plus chemotherapy (experimental arm) or chemotherapy alone, followed by surgery. Patients in the experimental arm with R0 resection received adjuvant nivolumab. Results: MRD detection rate was 9.6%. MRD after surgery or during adjuvant treatment was associated with inferior EFS and OS (HR: 10.2; 95%CI: 3.7-28.3 and HR: 10.0; 95%CI: 2.0-49.9, respectively). All patients with MRD-negative plasma samples in at least two time points were alive (HR: not estimable NE, p 0.001), with only one relapse (HR: 41.6; 95%CI: 5.0–348.8), corresponding to a patient relapsing with a single brain metastasis. MRD enhanced the prognostic value of pCR for both EFS (p0.001) and OS (p=0.015). Among non-pCR patients, MRD remained a significant prognostic marker (HR: 6.2; 95%CI: 2.2-17.1 and HR: 6.5; 95%CI: 1.3-32.5, for EFS and OS respectively). All non-pCR patients with MRD-negative results in at least two time points were alive (HR: NE, p=0.025), with one relapse (HR: 19.9; 95%CI: 2.4–165.6), corresponding to the aforementioned case. Conclusions: MRD may refine prognostic evaluation beyond pCR in resectable NSCLC undergoing perioperative chemoimmunotherapy.
Provencio et al. (Thu,) studied this question.