Perioperative Nivolumab and Chemotherapy in Stage III NSCLC

1. The pathological complete response rate for the experimental group was improved compared to the control group.

2. Progression-free survival and overall survival at 24 months were also improved in the experimental group with HR 0.47 and 0.43 respectively.

Evidence Rating Level: 1 (Excellent)

Study Rundown: The optimal treatment for non-small-cell lung cancer (NSCLC) diagnosed at stage IIIA or IIIB remains uncertain. Recent trials (NADIM, CheckMate 816) demonstrated the benefits of combining chemotherapy and immunotherapy, prompting this study (NADIM II) to compare nivolumab-platinum chemotherapy neoadjuvant treatment followed by adjuvant nivolumab, against standard neoadjuvant chemotherapy in resectable stage IIIA/IIIB NSCLC patients. The primary endpoint was pathological complete response (pCR) while secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. 93% of patients in the experimental group vs 69% in the control group underwent surgery with an RR 1.35. R0 resection was achieved in 94% in the experimental group vs 85% in the control group. The pCR was 37% in the experimental group and 7% in the control group with a RR of 5.34. A similar trend was observed with the major pathological response (RR 3.82) and the overall response (RR 1.56). At 24 months, PFS was 67.2% in the experimental group vs 40.9% in the control group with HR 0.47. OS at 24 months was 85.0% in the experimental group vs 63.6% in the control group with HR 0.43. Grade 3 or 4 adverse events for neoadjuvant treatment were noted in 19% in the experimental group vs 10% in the control group, with febrile neutropenia and diarrhea being the most common grade 3 or 4 adverse events in the experimental group (5% and 4% of patients, respectively). The strengths of this study included the follow-up time and the limitations included the number of participants. Overall, combining chemotherapy and nivolumab before and after surgery had a trend of achieving better outcomes (complete response, higher resection rates, and improved survival) compared to chemotherapy alone.

Click to read the study in NEJM

Relevant Reading: Overall Survival and Biomarker Analysis of Neoadjuvant Nivolumab Plus Chemotherapy in Operable Stage IIIA Non–Small-Cell Lung Cancer (NADIM phase II trial)

In-Depth [randomized controlled trial]: This open-label, multicenter, phase 2 trial randomly assigned adults with histologically documented previously untreated and resectable stage IIIA or stage IIIB NSCLC, in a 2:1 ratio to receive nivolumab plus chemotherapy (experimental group, 57 patients) or chemotherapy alone (control group, 29 patients), followed by surgery. The median duration of follow-up was 26.1 months. 93% of patients in the experimental group vs 69% in the control group underwent surgery with an RR 1.35 (95%CI, 1.05-1.74). R0 resection was achieved in 94% in the experimental group vs 85% in the control group. The pCR was 37% (95%CI, 24-51) in the experimental group and 7% (95%CI, 1-23) in the control group with a RR of 5.34 (95%CI, 1.34-21.23, p=0.02). This benefit was observed across all subgroups and was greater among patients with a PD-L1 tumor proportion score of 1% or greater. A similar trend was observed with the major pathological response (RR 3.82) and overall response (RR 1.56). At 24 months, PFS was 67.2% (95%CI, 55.8-81.0) in the experimental group vs 40.9% (95%CI, 26.2-63.6) in the control group with HR 0.47 (95%CI, 0.25-0.88). OS at 24 months was 85.0% (95%CI, 75.9-95.2) in the experimental group vs 63.6% (95%CI, 47.8-84.6) in the control group with HR 0.43 (95%CI, 0.19-0.98). Grade 3 or 4 adverse events for neoadjuvant treatment were noted in 19% in the experimental group vs 10% in the control group, with febrile neutropenia and diarrhea being the most common grade 3 or 4 adverse events in the experimental group (5% and 4% of patients, respectively). Overall, combining chemotherapy and nivolumab in the peri-operative period had a trend of achieving better outcomes (complete response, higher resection rates, and improved survival) compared to chemotherapy alone.

Image: PD

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