Neoadjuvant immunotherapy delivers better response in NSCLC

Patients with nonsmall cell lung cancer (NSCLC) who have been treated with neoadjuvant immunotherapy show greater response than those treated with neoadjuvant chemotherapy (CT), as shown in a study. Treatment-related adverse events (TRAEs) are similar between the two groups.

“Major pathologic response (MPR) rate and pathologic complete response (pCR) rate of neoadjuvant immunotherapy and neoadjuvant double-immunotherapy were significantly superior to neoadjuvant CT and neoadjuvant single-immunotherapy, respectively, for patients with NSCLC, showing that MPR rate and pCR rate were probably considered as alternative endpoints for survival benefit,” the authors said.

To assess the effectiveness and safety of neoadjuvant immunotherapy for NSCLC patients, the authors retrieved randomized controlled trials (RCTs) of the said treatment from electronic databases, eligible studies, previous systematic reviews and meta-analyses, guidelines, and conference abstracts. They then performed a meta-analysis using the State/SE 12.0 software.

Eleven RCTs met the eligibility criteria. Neoadjuvant immunotherapy resulted in a better objective response rate (ORR) than neoadjuvant CT (62.46 percent vs 41.88 percent; p=0.003). However, the ORR of neoadjuvant double-immunotherapy was not significantly different from that of neoadjuvant single-immunotherapy (15.74 percent vs 10.45 percent; p=0.387). [Am J Clin Oncol 2023;46:517-528]

Likewise, the rates of MPR and pCR were significantly greater with neoadjuvant immunotherapy and double-immunotherapy than with neoadjuvant CT alone and single-immunotherapy, respectively.

Neoadjuvant immunotherapy was also superior to neoadjuvant CT alone in terms of downstaging rate (40.16 percent vs 26.70 percent; p=0.060), surgical resection rate (83.69 percent vs 73.07 percent; p=0.231), and R0 resection rate (86.19 percent vs 77.98 percent; p=0.502). However, these differences did not reach statistical significance.

Postoperative complications rate did not increase with neoadjuvant immunotherapy relative to neoadjuvant CT alone (40.20 percent vs 41.30 percent; p=0.920). Similarly, neoadjuvant immunotherapy and double-immunotherapy did not result in higher incidences of TRAEs and grade 3 or higher TRAEs.

“In summary, neoadjuvant immunochemotherapy had better clinical efficacy than neoadjuvant CT for patients with NSCLC,” the authors said.

Before surgery

Patients with malignant tumours appeared to have better performance status, a more complete immune system, and a relatively large tumour volume prior to surgery.

“Moreover, the integrity of their blood vessels and lymphatic vessels ensures that the drugs can reach the lesions better, and the antigen load of antigen-presenting cells is relatively large, which makes the neoadjuvant immunotherapy cause a strong antitumor T-cell response,” the authors said.

Theoretically, the efficacy of neoadjuvant immunotherapy applied before surgery is superior to that of adjuvant immunotherapy applied after surgery. [Translat Lung Cancer Res 2020;9:2696-2715; Science 2016;351:1463-1469; Science 2020;367:eaax0182]

In the study by Lei and colleagues, “expert consensus on neoadjuvant immunotherapy for NSCLC” stressed that patients with resectable stage IB to IIIA NSCLC can undergo neoadjuvant immunotherapy alone or with platinum-based CT. [Translat Lung Cancer Res 2020;9:2696-2715]

“The long-term survival outcome of neoadjuvant immunotherapy for patients with NSCLC needs to be further confirmed to better guide clinical practice,” the authors said.