Neoadjuvant Chemoimmunotherapy in Patients with Resectable Non-small Cell Lung Cancer

Gutiérrez-Sainz, Laura; Cruz-Castellanos, Patricia; Higuera, Oliver; Castro-Carpeño, Javier de

doi:10.1007/s11864-021-00885-6

Cited by 10 publications

(10 citation statements)

References 44 publications

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“…In the present meta-analysis, MPR and PCR rates for patients with PD-L1 ≥1% (48.9% and 27.8%) and ≥50% (76.5% and 57.5%) were significantly higher than for patients with PD-L1 <1% (26.3% and 11.4%), suggesting a positive correlation between tumor pathologic response rate and PD-L1 level. Other biomarkers such as tumor mutational burden (TMB) ( 8 ), ctDNA ( 13 ), tumor-infiltrating lymphocytes (TILs) ( 25 ), and immune-related genes ( 62 ) were also reported to be correlated with MPR. Due to limited data, their predictive role needs to be further explored.…”

Section: Discussionmentioning

confidence: 99%

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

2022

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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.

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Section: Discussionmentioning

confidence: 99%

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

2022

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“…However, it is uncertain whether immunotherapy or chemotherapy is the main factor affecting the increased surgical difficulty. There is still no evidence suggesting that neoadjuvant chemoimmunotherapy increases the risk of surgical death ( 7 , 12 , 14 , 15 ).…”

Section: Discussionmentioning

confidence: 99%

“…Some other studies that explore the efficiency of the neoadjuvant chemoimmunotherapy on stage IIIA/B NSCLC are ongoing ( 10 ). However, there is currently no definitive conclusion on the feasibility of neoadjuvant chemoimmunotherapy for stage III NSCLC ( 5 , 6 , 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

Short-term outcomes of neoadjuvant sintilimab with chemotherapy in stage III non-small cell lung cancer: a case series

Fan¹,

Wang²,

Zhao³

et al. 2022

Transl Cancer Res TCR

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Background: Neoadjuvant chemoimmunotherapy seems to be a promising treatment option for stage III non-small cell lung cancer (NSCLC). Sintilimab, as a programmed death receptor-1 inhibitor, has exhibited a fine performance in treating NSCLC. However, the efficiency of sintilimab combined with chemotherapy for stage IIIA/IIIB NSCLC remains inconclusive. The purpose of this study was to share our experience on sintilimab in neoadjuvant chemoimmunotherapy for stage III NSCLC.Methods: This study retrospectively reviewed patients who received surgical resection following 1-3 cycles of neoadjuvant sintilimab (200 mg) with chemotherapy for stage III NSCLC between June 2020 and March 2022 in our center. Patients characteristics, surgical factors, surgery-related complications 30 days postoperatively, and treatment-related adverse events (TRAEs) before surgery were recorded through reviewing medical record data and telephone follow-up.Results: A total of eight patients were enrolled, including six cases of squamous cell carcinoma and two cases of adenocarcinoma. All of the patients received 1-3 cycles of neoadjuvant therapy. There were no treatment-related surgical delays. All patients underwent lobectomy, among which two underwent sleeve lobectomy and one received bronchoplasty. Five patients underwent open thoracotomy. Fibrosis of the primary tumor and lymph nodes was observed in all the cases. There were no surgery-related complications > grade 2 at 30 days postoperatively. According to the radiographic findings, one patient had stable disease and all of the others achieved a partial response. The median of maximum standardized uptake value change from baseline was a 52.75% reduction (range, 37.2-68.8%). Five patients achieved a major pathological response. R0 resection was achieved in all eight cases. One grade 4 event was observed. Neutropenia was the most common TRAE > grade 2 (3/8). There were no cases of treatment discontinuation or dose reduction due to TRAEs. Conclusions:The current study found that neoadjuvant sintilimab plus chemotherapy bring a high rate of major pathological response and acceptable TRAEs. Even though it increased the difficulties of surgery, there is still no evidence suggesting that it will brings additional surgical death. We believe that neoadjuvant sintilimab plus chemotherapy might be feasible for stage III NSCLC.

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“…A study concluded that pCR rate ranged from 0-10.5% in phase III neoadjuvant chemotherapy clinical trials, which was less effective than neoadjuvant chemoimmunotherapy [25]. Jia et al reported the e cacy and safety of neoadjuvant immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer

Liu

Zhang

et al. 2022

Preprint

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Background Currently, some studies reported neoadjuvant therapy for stage IB-III lung cancer could achieve pathological downstaging and surgical resection. Stage III non-small cell lung cancer (NSCLC) is a heterogeneous disease with different subtypes, multidisciplinary teams-led management, and a poor prognosis. However, the clinical benefits of stage III NSCLC in the neoadjuvant setting are still unclear. We performed a meta-analysis of published data on neoadjuvant chemoimmunotherapy in stage III NSCLC to systematically evaluate its efficacy and safety. Methods We searched the databases to identify eligible studies of neoadjuvant chemoimmunotherapy for stage III NSCLC. The primary outcomes mainly included pathological and radiological response outcomes, the feasibility of surgery, and the safety of the regimen. The pathological and radiological response included the rate of major pathologic response (MPR), complete pathologic response (pCR), radiological response outcomes, and R0 resection; The feasibility included the rate of surgical resection, conversion to thoracotomy, surgical complications, pathological downstaging of clinical disease stage. The safety included the incidence of treatment-related adverse events (TRAEs) and severe adverse events (SAEs). R 4.1.3 software was conducted for data analysis, and p < 0.05 was considered statistically significant. Sensitivity and heterogeneity analyses were performed. Results Nine trials containing a total of 382 populations were eligible for the meta-analysis, with the pooled surgical resection rate of 90%. Owing to the large heterogeneity of the single-rate meta-analysis, the random effect model was adopted. The estimated pooled prevalence of MPR was 56% (95%CI, 0.39–0.72) and of pCR was 39% (95%CI, 0.28–0.51). The pooled rate of TRAEs was 65% (95%CI, 0.17–0.99) and SAEs was 24% (95%CI, 0.05–0.49). Compared to neoadjuvant chemotherapy or immunotherapy, neoadjuvant chemoimmunotherapy achieved more pathological and radiological relief, and has a high surgical resection rate and low risk of conversion to thoracotomy and surgical complications, with poor tolerance of toxicity but rarely developing life-threatening adverse events. Conclusion In conclusion, neoadjuvant chemoimmunotherapy is suggested to be beneficial for stage III NSCLC, which provides a promising therapeutic strategy.

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Neoadjuvant Chemoimmunotherapy in Patients with Resectable Non-small Cell Lung Cancer

Cited by 10 publications

References 44 publications

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

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

Short-term outcomes of neoadjuvant sintilimab with chemotherapy in stage III non-small cell lung cancer: a case series

A systematic review and meta-analysis of neoadjuvant chemoimmunotherapy in stage III non-small cell lung cancer

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