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Comparison of Pathologic Response Between Nivolumab- and Pembrolizumab-Based Neoadjuvant Chemoimmunotherapy in NSCLC: A multi-center analysis
Objective: To compare pathologic responses between nivolumab‑ and pembrolizumab‑based neoadjuvant chemo‑immunotherapy (nCIT) for resectable, driver‑negative non‑small‑cell lung cancer (NSCLC), with prespecified stratification by histology and exploration of chemotherapy backbones.
Methods: We performed a multi‑center, retrospective cohort analysis of 232 patients with stage IB–IIIC EGFR/ALK wild‑type NSCLC who underwent nCIT followed by complete curative resection. Pathologic endpoints included residual viable tumor percentage (RVT%), major pathologic response (MPR), and pathologic complete response (pCR). Analyses were stratified by squamous cell carcinoma (SqCC) versus non‑SqCC and evaluated across common chemotherapy backbones (taxane‑ versus gemcitabine‑based regimens). Indirect comparative effectiveness was assessed using multivariable adjustment to account for case‑mix differences.
Results: Patients receiving nivolumab mostly had taxane-(56%, 84/151) or pemetrexed-based (42%, 64/151) regimens; patients receiving pembrolizumab predominantly had pemetrexed-(58%, 47/81) or gemcitabine-based (40%, 32/81) regimens. Median RVT% was lower with nivolumab than pembrolizumab (15 [IQR 0–60] vs 40 [5–60]) but not statistically significant (p=0.069). Pathologic responses favored nivolumab: MPR 49% (74/151) vs 35% (28/81), p=0.048; pCR 33% (50/151) vs 20% (16/81), p=0.046. In SqCC group, nivolumab‑based nCIT was associated with markedly lower RVT% (median 1 versus 20) and higher rates of pCR and MPR than pembrolizumab‑based nCIT. In non‑squamous disease, overall pathologic responses were comparable between agents across backbones (Table 1). Based on the adjusted pCR probability from the immune-checkpoint inhibitor X chemotherapy interaction model, taxane-based backbones showed the highest adjusted likelihood of pCR across histologies, whereas gemcitabine-based regimens were lowest, irrespective of the immune-checkpoint inhibitor (Figure 1).
Conclusions: In this multi‑center analysis of resectable NSCLC treated with nCIT, nivolumab‑based regimens demonstrated superior pathologic responses in squamous histology, while no clear difference emerged in non‑squamous tumors. Chemotherapy backbone selection also influenced response, favoring taxane‑based over gemcitabine‑based combinations. These data highlight a potential histology‑specific effect and support prospective trials to inform agent and backbone selection for neoadjuvant therapy.
YEONG JEONG JEON (1), Tae Hee Hong (2), Sehhoon Park (3), Chang Young Lee (4), Hong Kwan Kim (5), (1) Samsung Hospital, Seoul, South Korea, (2) Department of Thoracic and Cardiovascular Surgery, Yonsei University College of Medicine, Seoul, NA, (3) Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan Univer, Seoul, NA, (4) N/A, Seoul, South Korea, (5) N/A, N/A
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