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VIENNA -- The addition of neoadjuvant nivolumab (Opdivo) to chemotherapy significantly improved outcomes in patients with resectable stage IIIA-B non-small cell lung cancer, according to results from the trial.

The combination improved median progression-free survival (PFS) by a relative 52% compared with chemotherapy alone (P=0.025) at a median follow-up of 26.1 months, reported Mariano Provencio, MD, of Hospital Puerta de Hierro in Madrid, Spain, during a plenary session of World Conference on Lung Cancer (WCLC) here.

Nivolumab plus chemotherapy yielded 12-month PFS of 89.3% versus 60.7% for chemotherapy alone; at 24 months, PFS was 66.6% versus 43.3% in the two arms, respectively.

Overall survival was 98.2% with the combination compared with 82.1% in the chemotherapy group at 12 months, while 24-month rates were 84.7% and 63.4%, respectively (HR 0.40, 95% CI 0.17-0.93, P=0.034).

"NADIM II confirms the superiority of neoadjuvant nivolumab plus chemotherapy in patients with resectable stage IIIA-B NSCLC," Provencio said, adding that it is "the first clinical trial with a neoadjuvant immunotherapy-based combination for resectable stage IIIA-B [NSCLC] to show improved overall survival."

The trial enrolled 90 patients from 20 academic centers across Spain, 86 of whom were randomized to a treatment arm: 57 to receive nivolumab/chemotherapy and 29 to chemotherapy alone. Its primary outcome of pathological complete response (pCR) had been , showing significant improvement with nivolumab plus chemotherapy (36.8% vs 6.9%, OR 7.88, 95% CI 1.70-36.51).

Other results from NADIM II showed that patients who achieved pCR were all alive and free of disease at data cut-off.

Regarding surgery, 53 of the 57 patients in the nivolumab/chemotherapy arm (93%) underwent surgery compared with just 20 of 29 patients (69%) in the chemotherapy arm (OR 5.96, 95% CI 1.65-21.56). In addition, the proportion of patients who had R0 surgery was higher in in the nivolumab/chemotherapy arm at 92.5% compared with 65% in the chemotherapy arm (OR 6.60, 95% CI 1.67-26.02).

"A concern with any new adjuvant therapy is patients who progress after new adjuvant treatment, but also the proportion of patients who don't have surgery," commented Corinne Faivre-Finn, MD, PhD, of the University of Manchester, England, who served as study discussant at the WCLC session. "And the results are very favorable in NADIM II."

However, Faivre-Finn noted that the study took place in top academic centers in Spain and asked: "What is the applicability then in the real world? And is there a risk that patients will have either no surgery or incomplete resections after chemotherapy/immunotherapy in the real world?"

NADIM II served to validate the results of the NADIM and CHECKMATE 816 trials.

The phase II NADIM trial was a single arm trial that evaluated neoadjuvant nivolumab plus chemotherapy. It showed , as well as better pCR, in patients with resectable stage IIIA NSCLC.

The phase III CheckMate 816 trial confirmed the findings of NADIM, showing improved event-free survival in patients and a high rate of pCR in patients with resectable stage IIIB NSCLC.

NADIM II was an open-label, phase II, multicenter clinical trial in which patients with resectable clinical stage IIIA NSCLC, ECOG performance status of 0-1, and no known EGFR/ALK alterations were randomized to receive nivolumab 360 mg plus paclitaxel 200 mg/m² plus carboplatin AUC5 for three cycles every 21 days as neoadjuvant treatment followed by surgery, or paclitaxel 200 mg/m² plus carboplatin AUC5 for three cycles every 21 days followed by surgery.

Patients with R0 resection confirmed by pathological evaluation initiated adjuvant administration of nivolumab within the third to eighth week from surgery and for 6 months.

According to Provencio, baseline characteristics showed no statistically significant differences between the two arms.

In commenting on NADIM II, Faivre-Finn called the results impressive and agreed that they confirmed the findings of CheckMate 816. However, she also noted that overall survival was not a primary endpoint of the trial and that long-term overall survival data is needed to validate the impact of immunotherapy.

In addition, she noted that immunotherapy in the surgical and non-surgical curative setting has been a success. "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," she said.

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