Literature
Clinical Pearls & Morning Reports
Published August 9, 2023
How did the addition of nivolumab to neoadjuvant chemotherapy in the NADIM II trial affect outcomes for patients with resectable stage IIIA or IIIB non–small-cell lung cancer?
Provencio et al. conducted the NADIM II trial to assess neoadjuvant treatment with nivolumab plus platinum-based chemotherapy as compared with standard-of-care neoadjuvant chemotherapy in patients with resectable stage IIIA or IIIB non–small-cell lung cancer (NSCLC). Read the NEJM Original Article here.
Clinical Pearls
Q: Does preoperative chemotherapy substantially increase survival among patients with resectable stage IIIA or IIIB NSCLC?
A: NSCLC accounts for 80 to 85% of all lung cancers. Approximately 20% of patients with NSCLC receive a diagnosis of stage IIIA or IIIB disease. The most appropriate treatment for patients with stage IIIA or IIIB disease is not clear. Preoperative chemotherapy has been shown to significantly improve overall survival among patients with resectable NSCLC. However, the absolute difference in 5-year recurrence-free survival and overall survival between preoperative chemotherapy and surgery alone is only 5 percentage points, and outcomes remain poor, with a 5-year overall survival of approximately 36%.
Q: How did the addition of nivolumab to neoadjuvant chemotherapy in the NADIM II trial affect outcomes for patients with resectable stage IIIA or IIIB NSCLC?
A: Among patients with previously untreated stage IIIA or IIIB resectable NSCLC, neoadjuvant chemotherapy with nivolumab resulted in a significantly higher percentage of patients with a pathological complete response than chemotherapy alone. This benefit was observed across all subgroups. A greater benefit was observed among patients with a PD-L1 tumor proportion score of 1% or greater than among patients with a score of less than 1%. None of the patients who had had a pathological complete response had a relapse at 2 years of follow-up with 95.2% data maturity.
Morning Report Questions
Q: Did neoadjuvant nivolumab plus chemotherapy prolong survival as compared with neoadjuvant chemotherapy alone in NADIM II?
A: A benefit with respect to progression-free survival was observed in the experimental group. At 24 months, progression-free survival was 67.2% (95% CI, 55.8 to 81.0) in the experimental group and 40.9% (95% CI, 26.2 to 63.6) in the control group (hazard ratio for disease progression, disease recurrence, or death, 0.47; 95% CI, 0.25 to 0.88). A benefit with respect to overall survival was observed in the experimental group. Overall survival at 24 months was 85.0 (95% CI, 75.9 to 95.2) in the experimental group and 63.6% (95% CI, 47.8 to 84.6) in the control group (hazard ratio for death, 0.43; 95% CI, 0.19 to 0.98).
Q: What were some of the additional results of the trial?
A: The percentage of patients with a major pathological response was greater in the experimental group (53%; 95% CI, 39 to 66) than in the control group (14%; 95% CI, 4 to 32) (relative risk, 3.82; 95% CI, 1.49 to 9.79). The same was true for overall response: a response was observed in 75% (95% CI, 62 to 86) of the patients in the experimental group and in 48% (95% CI, 29 to 67) in the control group (relative risk, 1.56; 95% CI, 1.04 to 2.34). Neoadjuvant treatment with nivolumab plus chemotherapy resulted in a higher percentage of patients undergoing surgery than chemotherapy alone. A total of 53 patients (93%) in the experimental group and 20 patients (69%) in the control group underwent surgery (relative risk, 1.35; 95% CI, 1.05 to 1.74).