Adjuvant Nivolumab/Chemo Reduces Recurrence Risk in Resected NSCLC

Efficacy data from the trial revealed that among patients treated with chemo-immunotherapy, exhibited enhanced disease-free survival (DFS) outcomes vs chemotherapy alone, with 20.4% and 38.8% of each arm having relapsed as of data cut-off.

A clinically meaningful reduction in relapse rates was found with nivolumab (Opdivo)/chemotherapy vs chemotherapy alone in patients with completely resected stage IB-IIIA non–small cell lung cancer (NSCLC), according to findings from the first interim analysis of the phase 3 NADIM ADJUVANT trial (NCT04564157) presented at the 2025 IASLC World Conference on Lung Cancer (WCLC).

Efficacy data from the trial revealed that among patients treated with chemo-immunotherapy (n = 103), exhibited enhanced disease-free survival (DFS) outcomes vs chemotherapy alone (n = 103), with 20.4% and 38.8% of each arm having relapsed as of data cut-off. Although the median DFS rate was not reached (NR) in either arm after a median follow-up of 34.0 months (IQR, 32.6-36.6), the 24- and 36-month rates, respectively, were 77.7% vs 67.9% and 73.3% vs 59.9%. The 3-year HR was 0.65 (95% CI, 0.40-1.07; P = .085) with a 57% data maturity.

Additionally, a sensitivity analysis for cancer-specific DFS revealed that the 24- and 36-month rates in the experimental chemo-immunotherapy and control chemotherapy-only arms were 82.6% vs 68.6% and 77.9% vs 62.5%, respectively (HR, 0.54; 95% CI, 0.32-0.93; P = .025). Furthermore, subgroup analyses revealed that patients experienced greater benefit with chemo-immunotherapy having complete adjuvant therapy (HR, 0.55; 95% CI, 0.33-0.94) vs those who did not (HR, 2.03; 95% CI, 0.48-8.51). Additionally, those who completed overall treatment experienced a greater benefit with chemo-immunotherapy (HR, 0.53; 95% CI, 0.28-0.99) vs those who did not (HR, 0.65; 95% CI, 0.29-1.49).

“These are immature results because we have to consolidate the results. We have a [57%] maturity of the data, but we have a meaningful reduction in relapse,” Mariano Povencio, MD, chief of the Medical Oncology Department at the Hospital Universitario Puerta de Hierro Majadahonda, stated in the presentation.“The sensitivity analysis of the cancer-specific DFS was clearly significant. The tolerability and safety were consistent with previous data of this treatment from other clinical situations.”

The phase 3 trial enrolled 210 patients with histologically confirmed IB, II, or IIIA NSCLC per American Joint Committee on Cancer (AJCC) v8 criteria who had undergone an R0 resection and had not previously been treated with prior therapy and randomly assigned them 1:1 to receive nivolumab plus chemotherapy or chemotherapy alone. Treatment consisted of an adjuvant phase and a maintenance phase, the former of which consisted of 360 mg of nivolumab and chemotherapy every 3 weeks for 4 cycles or chemotherapy alone. Maintenance consisted of nivolumab at 480 mg every 4 weeks for 6 months or observation every 12 weeks for 6 months, with 5 years of follow-up thereafter.

In the experimental and control arms, the median age was 65.2 years (range, 40.0-82.0) vs 65.7 years (range, 46.0-83.0), and most patients were male (74.8% vs 76.7%) and Caucasian (99% vs 96.1%). Most patients had an ECOG performance score of 0 (51.5% vs 56.3%), a former or current smoking history (94.2% vs 94.2%), and had an adenocarcinoma histology (63.1% vs 65%). A total of 96.1% vs 92.2% of patients had comorbidities, the most common of which included hypertension (50.5% vs 37.9%), dyslipidemia (41.7% vs 37.9%), and chronic obstructive pulmonary disease (COPD; 30.1% vs 24.3%).

A total of 39.2% vs 44.0% of patients had a PD-L1 over 50%, 74.8% vs 73.8% had EGFR-mutant disease, and 53.4% vs 60.2% had ALK-positive disease. Most patients had stage IIB disease (45.6% vs 51.5%), N0 disease (49.5% vs 52.4%), and a lobectomy (79.6% vs 79.6%).

The primary end point of the trial was DFS. Secondary end points included overall survival and the safety and tolerability of chemo-immunotherapy. An exploratory analysis examined minimal residual disease, and a sensitivity analysis for DFS included lung cancer-specific survival and DFS from the last cycle of chemotherapy.

Of note, a 90-day after surgery LANDMARK analysis revealed 24- and 36-month DFS rates of 79.2% vs 74.7% and 67.0% vs 60.1% in the experimental and control arms, respectively (3-year HR, 0.60; 95% CI, 0.37-0.99; P = .048). Additionally, a sensitivity analysis for DFS following the last chemotherapy cycle showed 24- and 36-month rates of 80.4% vs 75.7% and 66.7% vs 59.1%, respectively (3-year HR, 0.55; 95% CI, 0.33-0.94; P = .029).

Reference

Provencio M, Bernabé R, Nadal E, et al. A phase III clinical trial of adjuvant chemotherapy vs chemo-immunotherapy for stage IB-IIIA completely resected non-small cell lung cancer (NSCLC) patients: first interim analysis. Presented at: IASLC 2025 World Conference on Lung Cancer. September 6-9, 2025. Barcelona, Spain. Abstract PL03.07