medwireNews: The phase 2 NADIM study points to the potential of neoadjuvant treatment with nivolumab plus platinum-based chemotherapy in treatment-naïve patients with resectable, stage IIIA non-small-cell lung cancer (NSCLC).
“Our results showed that in this high-risk patient group, which included a high proportion of patients with multiple stage IIIA (N2) disease, favourable pathological responses and downstaging, and progression-free survival and overall survival at 24 months were observed after neoadjuvant nivolumab plus standard chemotherapy,” comment the investigators.
And they emphasize that the administration of neoadjuvant chemoimmunotherapy did not delay surgery.
In total, 46 patients with previously untreated, operable NSCLC (74% N2) were given nivolumab 360 mg alongside paclitaxel 200 mg/m2 plus carboplatin AUC 6 (6 mg/mL per min) on the first day of three 21-day cycles. Forty-one patients went on to receive surgery, 37 of whom received at least one cycle of adjuvant treatment with nivolumab and were included in the per-protocol population.
The researchers report that 35 of the participants who had surgery remained progression free after a median follow-up of 24 months, and the median durations of progression-free survival (PFS) and overall survival (OS) had not been reached at data cutoff.
Among the 46 patients who received neoadjuvant treatment, the 12- and 24-month PFS rates were 95.7% and 77.1%, respectively, with corresponding rates of 100% and 87.9% for the per-protocol population. And the OS rates at these timepoints were 97.8% and 89.9%, respectively, for all patients who received neoadjuvant treatment, and were 100% and 97.3%, respectively, for those included in the per-protocol population.
The RECIST overall response rate to neoadjuvant treatment was 76%, including a complete response in 4%. Nearly a quarter (24%) of patients had stable disease and none had progressive disease during neoadjuvant treatment.
Furthermore, 83% of the patients who underwent surgery had a major pathologic response, with the majority (63%) achieving complete pathologic responses and 90% achieving pathologic downstaging of clinical disease stage.
Neoadjuvant chemoimmunotherapy was associated with grade 3 or higher treatment-related adverse events (TRAEs) in 30% of patients, most commonly increased lipase (7%) and febrile neutropenia (7%). No AEs were associated with treatment discontinuation, dose reduction, surgery delay, or death.
However, AEs precluded three patients from receiving adjuvant nivolumab, and 14% discontinued adjuvant nivolumab owing to TRAEs.
A total of 29% of patients had postoperative complications, with respiratory infections (10%), cardiac arrhythmia (7%), and air leakage (5%) being the most frequent.
“One of the main concerns regarding neoadjuvant therapy is risk of preoperative complications; however, we showed that treatment was well tolerated, was not associated with delays in surgery, and led to complete resection in all patients who had surgery,” say Mariano Provencio (Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain) and colleagues in The Lancet Oncology.
And they conclude: “[N]eoadjuvant chemoimmunotherapy represents a promising therapeutic option for patients with resectable stage IIIA NSCLC, which requires confirmation in future randomised clinical trials, such as the ongoing phase 2 NADIM II trial (NCT03838159) and phase 3 Checkmate 77T trial (NCT04025879).”
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