The efficacy of neoadjuvant nivolumab plus chemotherapy in resectable stage IIIA non–small-cell lung cancer (NSCLC) has been supported by results presented at ASCO 2022 showing unprecedentedly high survival rates.
Three year data from the NADIM trial showed that overall survival was almost three times that reported in the historical series, according to study investigators from Spain.
Their study findings also backed the usefulness of ctDNA as an early surrogate end point in the context of neoadjuvant treatment.
In the phase 2 multicentre trial, 46 patients deemed eligible for surgical resection were treated with neoadjuvant paclitaxel, carboplatin plus nivolumab for three 21-day cycles, followed by adjuvant nivolumab monotherapy for one year.
The authors said they had previously reported the primary endpoint pathologic complete response (pCR) rate results, showing that the addition of neoadjuvant nivolumab to chemothjerapy significantly increased the pCR rate compared to 36.2%, compared to 6.8% with neoadjuvant chemotherapy alone (Relative Risk 5.25 [99% CI 1.32-20.87]; P = 0.0071).
New findings reported at ASCO showed that overall survival at 36 months was 81.9% (95% confidence interval [CI] = 66.8%–90.6%) in the intention-to-treat population (46 patients) and 91.0% (95% CI = 74.2%–97.0%) in the per-protocol population of 37 patients.
“These are unprecedentedly high survival rates in patients with stage IIIA NSCLC and have not been reported in prior studies evaluating neoadjuvant approaches,” the authors said.
They also noted that in the 12 patients who showed disease progression, the median time to progression was 19.4 months, which exceeded that of the overall follow-up from the previous series
An additional finding was that patients with low ctDNA levels (< 1% mutant allele fraction) at baseline had significantly improved progression-free survival (adjusted hazard ratio [HR] = 0.20, P = .006) and OS (adjusted HR = 0.07, P = .002) compared with patients with higher ctDNA levels. They added that ctDNA levels outperformed radiologic assessments in the prediction of survival.
The study investigators said they had previously reported a modest increase in treatment related adverse effects in patients who received nivolumab in addition to chemotherapy, and none of them were associated with delayed surgery or death.
Neoadjuvant treatment with nivolumab enable more patients to have resection, they said, reporting surgery for 91% of pts treated with nivolumab and chemo and 69% with chemo alone.
“This study confirms the superiority of the chemo-immuno combination in patients with resectable stage IIIA NSCLC in terms of pCR, as well as the feasibility of surgery, with a moderate increase in grade 3-4 toxicity. Thus, this treatment should become the standard of care in these patients.”