In patients with resectable, stage IIIA non–small cell lung cancer (NSCLC), the addition of neoadjuvant nivolumab to platinum-based chemotherapy significantly improved overall survival compared with neoadjuvant chemotherapy alone, according to data presented by Mariano Provencio, MD, PhD, at the International Association for the Study of Lung Cancer (IASLC) 2022 World Conference on Lung Cancer (WCLC) in Vienna.1 NADIM II is reportedly the first clinical trial with a neoadjuvant immunotherapy–based combination for resectable stage IIIA–B NSCLC to show improved overall survival.
Results of the randomized phase II, multicenter trial showed an overall survival rate of 85.3% at 24 months with neoadjuvant nivolumab plus chemotherapy vs 64.8% with neoadjuvant chemotherapy alone. In addition, the pathologic complete response rate was 36.2% for patients receiving neoadjuvant chemoimmunotherapy compared with 6.8% in the control arm.
“NADIM II demonstrates that the efficacy of nivolumab in combination with platinum-based chemotherapy in patients with resectable, stage IIIA NSCLC is supported by survival data,” said Dr. Provencio, Scientific Director of the Health Research Institute of the Puerta de Hierro University Hospital and Professor of Medicine at the Autonomous University of Madrid. “The benefit is especially pronounced in patients whose tumors express PD-L1 and in those patients achieving pathologic complete response.”
Mariano Provencio, MD, PhD
As Dr. Provencio explained, multimodality treatment is necessary for patients with stage IIIA (N2) NSCLC, but outcomes remain poor, with 5-year survival of approximately 36%.
“The absolute improvement in overall survival with neoadjuvant chemotherapy is approximately 5%, and the pathologic response rate is very low, at only 4%,” said Dr. Provencio.
According to Dr. Provencio, neoadjuvant immunotherapy for resectable NSCLC demonstrated activity in several single-arm, phase II studies. Data from the single-arm NADIM trial showed an overall survival almost three times that reported in the historical series and an improved percentage of patients with pathologic complete response.
NADIM II is an open-label, randomized, two-arm clinical trial sponsored by the Spanish Lung Cancer Group. Patients with resectable clinical stage IIIA NSCLC, an Eastern Cooperative Oncology Group performance status of 0 to 1, and no known EGFR/ALK alterations were randomly assigned to receive nivolumab at 360 mg plus paclitaxel at 200 mg/m2 plus carboplatin for three cycles every 21 days (± 3 days) as neoadjuvant treatment followed by surgery or chemotherapy alone followed by surgery.
Patients with complete resection, confirmed by pathologic evaluation, initiated adjuvant administration of nivolumab (480 mg every 4 weeks) within weeks 3 to 8 from surgery and continued this agent for 6 months.
Initial results of the study showed a significant improvement in the primary endpoint of pathologic complete response with neoadjuvant chemoimmunotherapy vs chemotherapy alone (36.8% vs 6.9%; P = .0068). During WCLC 2022, Dr. Provencio presented the results of the secondary endpoints of progression-free and overall survival rates at 24 months.
Complete Pathologic Response and PD-L1 Expression
With a median follow-up of 26.1 months, the rate of progression-free survival was 66.6% with nivolumab plus chemotherapy vs 42.3% with chemotherapy alone (hazard ratio [HR] = 0.48; P = .025). Median follow-up time was 26.1 months.
The addition of neoadjuvant nivolumab to chemotherapy also significantly improved the overall survival rate vs chemotherapy alone at both 12 months (98.2% vs 82.1%; P = .007) and 24 months (84.7% vs 63.4%; P = .014).
Of note, progression-free and overall survival correlated strongly with pathologic complete response. As Dr. Provencio reported, 100% of patients who achieved a complete pathologic response (R0) were alive at 24 months, and none of these patients had disease progression.
In the experimental arm, PD-L1 expression (≥ 1%) also identified patients with significant improvement in progression-free survival. “This trial confirms the superiority of neoadjuvant nivolumab plus chemotherapy in combination in patients with resectable stage IIIA–B NSCLC,” said Dr. Provencio. “The combination also maintained a tolerable safety profile... and did not impede the feasibility of surgery.”
DISCLOSURE: Dr. Provencio disclosed financial relationships with AstraZeneca, Roche, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Merck Sharp & Dohme, Takeda, and Thermo-Fisher.
1. Provencio M, Serna R, Nadal E, et al: Progression free survival and overall survival in NADIM II study. 2022 World Conference on Lung Cancer. Abstract PL03.12. Presented August 8, 2022.
The first discussant of the NADIM II study, Corinne Faivre-Finn, MD, PhD, Professor of Thoracic Radiation Oncology, University of Manchester, and Honorary Consultant Clinical Oncologist at The Christie NHS Foundation Trust, Manchester, England, called the results “very impressive” but noted that...