Neoadjuvant immune checkpoint inhibitors in resectable non-small-cell lung cancer: a systematic review

Abstract

Background The neoadjuvant use of immune checkpoint inhibitors (ICIs) in resectable non-small-cell lung cancer (NSCLC) is currently an area of active ongoing research. The place of neoadjuvant ICIs in the treatment guidelines needs to be determined. We carried out a systematic review of published data on neoadjuvant ICIs in resectable NSCLC to study its efficacy and safety. Patients and methods A literature search was carried out using the MEDLINE (PubMed) and Embase databases to retrieve articles and conference abstracts of clinical trials measuring the efficacy [major pathological response (MPR) and pathological complete response (pCR)] and safety (failure to undergo resection, surgical delay, treatment-related adverse events (trAEs) grade ≥3) of neoadjuvant immunotherapy in resectable NSCLC until July 2021. Results Nineteen studies with a total of 1066 patients were included in this systematic review. Neoadjuvant immunotherapy was associated with improved pathological response rates, especially in combination with chemotherapy. Using mono ICI, dual therapy–ICI, chemoradiation–ICI, radiotherapy–ICI, and chemo–ICI, the MPR rates were 0%-45%, 50%, 73%, 53%, and 27%-86%, respectively. Regarding pCR, the rates were 7%-16%, 33%-38%, 27%, 27%, and 9%-63%, respectively. Safety endpoints using monotherapy–ICI, dual therapy–ICI, chemoradiation–ICI, radiotherapy–ICI, and chemo–ICI showed a failure to undergo resection in 0%-17%, 19%-33%, 8%, 13%, and 0%-46%, respectively. The trAEs grade ≥3 rates were 0%-20%, 10%-33%, 7%, 23%, and 0%-67%, respectively. Conclusion In patients with resectable NSCLC stage, neoadjuvant immunotherapy can improve pathological response rates with acceptable toxicity. Further research is needed to identify patients who may benefit most from this approach, and adequately powered trials to establish clinically meaningful benefits are awaited.

Thyroid dysfunction induced by immune checkpoint inhibitors and tumor progression in neoadjuvant therapy for Non-Small Cell Lung Cancer: a case report and literature review

“…[16, 7,9,[17][18][19][20][21][22]. Disease progression, inadequate lung function, unresectable disease, adverse events, location of tumor, or patient refusal might be the reasons that patient cannot undergo resection [11]. In our case, the disease progression contributed to the failure to undergo resection, which suggested that there was a great need for biomarker to predict the e cacy of the immunotherapy.…”

“…Several trials exploring the e cacy and safety of monotherapy ICI or in combination with chemotherapy in neoadjuvant treatment of NSCLC have shown promising results. However, the immune-related adverse events (irAEs) and the poor response to immunotherapy aroused great concern [11,15]. Our study has presented a case of irAEs and tumor progression after the treatment of the PD-1 inhibitor pembrolizumab in combination with chemotherapy.…”

“…However, there are several considerations that ICIs might have some signi cant toxicities resulting in surgery delay and/or the intraoperative complications. Tumor progression might occur in some cases due to the toxicities or poor e cacy [10,11].…”

Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy

“…Clinical studies (8)(9)(10) have unleashed the promise of neoadjuvant immunotherapy. More than 90% of NSCLC patients were able to undergo surgery within the planned timeframe after neoadjuvant immunotherapy (11). In addition, RNA vaccine could be another effective immunotherapy, which drives immunity by the induction of strong CD4 + and CD8 + T-cell immunity against the vaccine antigens to kill cancer cells (12).…”

The Evolving Role of Immunotherapy in Stage III Non-Small Cell Lung Cancer

“…Subsequent trials of neoadjuvant monotherapy PD-(L)1 inhibitors in resectable NSCLC patients were not as encouraging and found to have lower MPR rates of approximately 20%, similar to that seen with chemotherapy ( Table 2 ) [ 20 , 21 , 22 , 23 , 24 , 25 ].…”