NADIM II suggests PFS, OS benefits of nivolumab + chemo in resectable NSCLC

Adding nivolumab to paclitaxel-carboplatin chemotherapy in the neoadjuvant setting boosted progression-free survival (PFS) and overall survival (OS) in patients with resectable stage IIIA–B non-small cell lung cancer (NSCLC), according to results of the phase II NADIM II trial from Spain.

“NADIM II confirms the superiority of the neoadjuvant nivolumab + chemotherapy combination in patients with resectable stage IIIA–B NSCLC,” said Dr Mariano Provencio from the Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, at WCLC 2022.

The 86 study participants had locally advanced, potentially resectable stage IIIA–IIIB NSCLC, ECOG performance status 0–1, and no EGFR/ALK alterations. They were randomized to receive three cycles of neoadjuvant nivolumab (360 mg) + paclitaxel (200 mg/m²) + carboplatin (AUC 5) Q3W (n=57; median age 63 years, 37 percent female) or paclitaxel (200 mg/m²) + carboplatin (AUC 5) Q3W (n=29; median age 62 years, 45 percent female) followed by surgery. Patients with confirmed R0 resection in the nivolumab + chemo arm received adjuvant nivolumab (480 mg Q4W) for 6 months.

The most common cancer histology was adenocarcinoma (43.9 percent [nivolumab + chemo] vs 37.9 percent [chemo alone]) and squamous cell carcinoma (36.8 percent vs 48.3 percent). Patients primarily had N2 stage disease (71.9 percent vs 55.2 percent), and tumour size was a median 43 vs 52 mm.

At a median follow-up of 26.1 months, PFS was significantly improved in patients assigned to nivolumab + chemo compared with chemo alone (median not reached vs 18.3 months; hazard ratio [HR], 0.48, 95 percent confidence interval [CI], 0.25–0.91; p=0.025), with estimated 2-year PFS rates of 66.6 percent vs 42.3 percent. [WCLC 2022, abstract 1988]

OS was also significantly improved with the nivolumab + chemo combination vs chemo alone (median not reached in both groups; HR, 0.40, 95 percent CI, 0.17–0.93; p=0.034), with 2-year OS rates of 84.7 percent vs 63.4 percent.

Significantly more patients in the nivolumab + chemo than chemo-alone arm had definitive surgery (93.0 percent vs 69.0 percent; odds ratio [OR], 5.96; p=0.00807), R0 (92.5 percent vs 65.0 percent; OR, 6.60; p=0.007), and downstaging of disease (69.8 percent vs 40.0 percent; OR, 3.47; p=0.04).

Previously published results showed that the rate of pathological complete response (pCR) was also significantly improved with nivolumab + chemo vs chemo alone (36.2 percent vs 6.8 percent; OR, 7.88, 95 percent CI, 1.70–36.51; p=0.0068). There were no deaths or incidents of disease progression among patients who achieved pCR. [J Clin Oncol 2022;40:8501]

The combination had a tolerable safety profile with a moderate increase in grade 3–4 toxicity, said Provencio.

“Approximately 20 percent of patients with NSCLC are diagnosed with stage IIIA (N2) disease,” noted Provencio. The prognosis for this disease is poor, with a 5-year OS rate of about 36 percent. While pre-operative chemotherapy has shown OS benefits, the absolute 5-year survival improvement is only about 5 percent, he said.

“NADIM II is the first clinical trial with a neoadjuvant immunotherapy-based combination (nivolumab + chemo) for resectable stage IIIA–B NSCLC to show improved OS,” said Provencio. “[The treatment combination] did not impede the feasibility of surgery,” he added.

The applicability of the findings in the real world is yet to be ascertained, said discussant Professor Corinne Faivre-Finn from The Christie NHS Foundation Trust and University of Manchester, Manchester, UK. Areas to explore include whether there is a risk that patients would have no surgery or R1 or R2 resections following chemo-immunotherapy, as well as the patient population that would most benefit from the combination strategy and the role of biomarkers in identifying this group.