Author: By Lynda Williams, Senior medwireNews Reporter
medwireNews: Both progression-free survival (PFS) and overall survival (OS) are better in patients with resectable stage IIIA–B non-small-cell lung cancer (NSCLC) when nivolumab is added to neoadjuvant chemotherapy and given after surgery, indicate phase II trial findings reported at the IASLC World Conference on Lung Cancer 2022 in Vienna, Austria.
“NADIM II confirms superiority of neoadjuvant nivolumab plus chemotherapy combination” in this population, said presenting author Mariano Provencio, from the Hospital Universitario Puerta de Hierro-Majadahonda in Madrid, Spain.
The trial previously met the primary endpoint of a significantly better pathological complete response rate with three cycles of neoadjuvant nivolumab 360 mg plus paclitaxel and carboplatin, followed by 6 months of adjuvant nivolumab 480 mg when compared with only neoadjuvant chemotherapy.
For the current analysis, conducted after a median follow-up of 26.1 months, the secondary endpoint of PFS was significantly better with the nivolumab regimen than chemotherapy alone, with median duration unreached versus 18.3 months and a hazard ratio (HR) of 0.48.
The PFS rates were significantly higher in the nivolumab-treated patients than controls at 12 months (89.3 vs 60.7%) and 24 months (66.6 vs 42.3%) of follow-up, the presenter said.
Although the median duration of OS was unreached in both the nivolumab and control arms, the HR for death was a significant 0.40. And both the 12-month (98.2 vs 82.1%) and 24-month (84.7 vs 63.4%) rates of OS significantly favoured the use of nivolumab.
Mariano Provencio commented that nivolumab “did not impede the feasibility of surgery” and was associated with “a modest increase” in grade 3 or 4 adverse events compared with chemotherapy alone.
“NADIM II is the first clinical trial with a neoadjuvant immunotherapy-based combination (nivolumab + chemotherapy) for resectable stage IIIA-B to show improved OS”, he concluded.
The discussant for the congress session congratulated the NADIM II investigators on their “very impressive” results, validating those of the phase III CheckMate 816 trial in a similar resectable NSCLC population of patients given neoadjuvant nivolumab plus chemotherapy.
However, Corinne Faivre-Finn, from The Christie NHS Foundation Trust and University of Manchester in the UK, cautioned about the potential risk of using neoadjuvant immunotherapy in patients who are unsuitable for surgery.
She also emphasized the “major implementation challenges” required to facilitate rapid next-generation sequencing, assessment of baseline and clearance circulating tumour DNA and PD-L1 testing for neoadjuvant immunotherapy use.
The discussant concluded that the “time is probably ripe for a clinical trial comparing a surgical to a non-surgical approach with good integration of biomarkers for patient selection.”
A second abstract on NADIM II was presented at the conference by Atocha Romero, also from Hospital Universitario Puerta de Hierro-Majadahonda, who reported that baseline circulating tumour (ct)DNA levels “clearly identified patients at high risk of death and progression.”
ctDNA analysis of 53 patients who underwent resection after nivolumab and chemotherapy and 20 patients who had surgery after chemotherapy alone showed a significant and positive association between pretreatment ctDNA levels and tumour size of at least 70 mm.
Moreover, pretreatment ctDNA levels were significantly associated with PFS and OS regardless of the mutant allele fraction (MAF) threshold used, the investigator said, finding that a MAF cutoff of 5% “added a significant degree of prognostic information to the clinical stage” for both survival outcomes.
PL03.12: Provencio M, Serna R, Nadal E, et al. Nivolumab + chemotherapy vs chemotherapy as neoadjuvant treatment for resectable IIIA-B NSCLC. Progression-free survival and overall survival results from the phase 2 NADIM II trial. IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August.
MA06.03: Romero A, Serna-Blasco R, Nadal E, et al. Pre-treatment ctDNA levels significantly predicts of OS and PFS in NADIM II trial. IASLC World Conference on Lung Cancer 2022; Vienna, Austria: 6–9 August.
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