Neoadjuvant immunotherapy and neoadjuvant chemotherapy in resectable non-small cell lung cancer: A systematic review and single-arm meta-analysis

Abstract

BackgroundIt remains uncertain whether neoadjuvant immune checkpoint inhibitor (nICI) is superior to neoadjuvant chemotherapy (nCT) in resectable non-small cell lung cancer. In addition, there are outstanding questions for nICI such as the ideal treatment mode and predictors.MethodsPubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible single-arm or multi-arm trials until 31 December 2021. The primary outcomes of interest were major pathological response (MPR) and pathological complete response (pCR). The random-effect model was used for statistical analysis.ResultsTwenty-four trials of nICI (n = 1,043) and 29 trials of nCT (n = 2,337) were identified. nICI combination therapy was associated with higher MPR (63.2%, 95% CI: 54.2%–72.1%) and pCR (35.3%, 95% CI: 27.4%–43.3%) rates compared to nCT (16.2%, 95% CI: 7.5%–25.0%, P < 0.001 and 5.5%, 95% CI: 3.5%–7.5%, P < 0.001) and nICI monotherapy (23.3%, 95% CI: 12.7%–33.8%, P < 0.001, and 6.5%, 95% CI: 1.7%–11.2%, P < 0.001). As for safety, nICI monotherapy had the best tolerability; nICI combination showed a similar surgical resection rate and higher R0 resection rate compared to nCT. PD-1 inhibitor and high PD-L1 expression (≥1% or ≥50%) were correlated with higher MPR and pCR rates compared to PD-L1 inhibitor and PD-L1 expression <1%.ConclusionsnICI combination therapy is associated with higher MPR and pCR rates compared to nCT and nICI monotherapy. PD-1 inhibitor seems to be superior to PD-L1 inhibitor. PD-L1 status appears to be predictive of MPR and pCR for patients receiving nICI.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=278661, CRD42021278661.

Clinical Stage III NSCLC Patients Treated with Neoadjuvant Therapy and Surgery: The Prognostic Role of Nodal Characteristics

“…These data reflect the importance of lymph node and mediastinal downstaging in this class of patients [10,12] and the repercussions linked to the absence of lymph nodes analysis for the administration of adjuvant therapy in the nearest future.…”

“…More specifically, pathological complete response and N2 downstaging were found to be significant prognostic factors in these patients and the metabolic response was considered more reliable compared to morphological evaluation only [10,11]. In recent years, different neoadjuvant protocols, including immunotherapy or target agents, have been introduced with encouraging results in terms of major, complete and nodal pathological response with consequent significant survival benefits [12,13].…”

Prognostic role of lymph node micrometastasis in pN0 esophageal cancer: A meta-analysis

“…[3] Although most patients with early and intermediate-stage esophageal cancer receive the systemic surgical and neoadjuvant/adjuvant therapies, a considerable proportion of esophageal cancer patients will still experience the recurrence and metastasis after the surgery, even among patients without lymph node metastasis. [4,5] Therefore, the causes and mechanisms of postoperative recurrence and metastasis in esophageal carcinoma patients need to be further investigated.…”

What is the ideal endpoint in early-stage immunotherapy neoadjuvant trials in lung cancer?

“…Here we review the advantages and disadvantages of currently available endpoints for clinical trials of neoadjuvant regimens in NSCLC. [7][8][9][10][11] Potential primary endpoints Overall survival: Improvement in OS remains among the primary goals of most novel anticancer therapies. OS is defined as the time from randomization or treatment start to death from any cause.…”