Efficacy and safety of immune checkpoint inhibitors for individuals with advanced EGFR-mutated non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitors: a systematic review, meta-analysis, and network meta-analysis.

BACKGROUND: The clinical benefits of immune checkpoint inhibitor (ICI)-based treatments in treating individuals with advanced EGFR-mutated non-small-cell lung cancer (NSCLC) who have progressed on EGFR tyrosine-kinase inhibitors (TKIs) remain controversial. We aimed to review the literature to comprehensively investigate the individual and comparative clinical outcomes of various ICI-based treatment strategies in this population. METHODS: In this systematic review and meta-analysis, we used single-arm, pairwise, and network meta-analytical approaches. We searched PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrials.gov, and relevant international conference proceedings from database inception to Jan 31, 2024, without language restrictions, to identify eligible clinical trials that assessed ICI-based treatments for individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs. Studies considered eligible were published and unpublished phase 1, 2, or 3 clinical trials enrolling participants with histologically or cytologically confirmed advanced EGFR-mutated NSCLC who had progressed after at least one EGFR-TKI treatment, and that evaluated ICI-based treatment strategies on at least one of the clinical outcomes of interest. The primary outcome analysed was progression-free survival. The protocol is registered with PROSPERO, CRD42021292626. FINDINGS: 17 single-arm trials and 15 randomised controlled trials, involving 2886 participants and seven ICI-based treatment strategies (ICI monotherapy, ICI plus chemotherapy [ICI-chemo], ICI plus antiangiogenesis [ICI-antiangio], ICI plus antiangiogenesis plus chemotherapy [ICI-antiangio-chemo], dual ICIs [ICI-ICI], dual ICIs plus chemotherapy [ICI-ICI-chemo], and ICI plus EGFR-TKI [ICI-TKI]), were included. Three of these strategies-ICI monotherapy, ICI-antiangio-chemo, and ICI-chemo-had sufficient data across the included studies to perform a pairwise meta-analysis. The pairwise meta-analysis showed that, compared with chemotherapy, ICI monotherapy led to shorter progression-free survival (hazard ratio [HR] 1·73 [95% CI 1·30-2·29], I2=0%), whereas ICI-antiangio-chemo (HR 0·54 [0·44-0·67], I2=0%) and ICI-chemo (HR 0·77 [0·67-0·88], I2=0%) prolonged progression-free survival. The network meta-analysis showed that ICI-antiangio-chemo yielded the best progression-free survival results, with substantial benefits over ICI-chemo (HR 0·71 [95% credible interval 0·59-0·85]), ICI monotherapy (HR 0·30 [0·22-0·41]), and non-ICI treatment strategies including antiangio-chemo (HR 0·76 [0·58-1·00]) and chemotherapy alone (HR 0·54 [0·45-0·64]). ICI-antiangio-chemo was associated with higher risks of both any-grade and grade 3 or worse adverse events over ICI-chemo and chemotherapy in the network meta-analysis. INTERPRETATION: For individuals with advanced EGFR-mutated NSCLC who progressed on EGFR-TKIs, ICI-antiangio-chemo was identified as the optimal treatment option. The toxicity of this treatment was acceptable but needs careful attention. ICI-chemo showed appreciably greater efficacy than the standard-of-care chemotherapy. These findings clarified the roles of ICI-based treatment strategies in this difficult-to-treat refractory population, potentially complementing recent guidelines. FUNDING: None.

Preoperative immunochemotherapy for locally advanced non-small cell lung cancer: an analysis of the clinical outcomes, optimal number of cycles, and peripheral immune markers.

Background: This retrospective study aimed to evaluate the real-world efficacy of neoadjuvant immunochemotherapy in locally advanced stage III non-small cell lung cancer (NSCLC), with a particular focus on analyzing the optimal treatment cycle and peripheral immune markers. Methods: Eligible patients with biopsy-confirmed stage III NSCLC who underwent neoadjuvant immunochemotherapy between January 1st, 2018 and March 30th, 2021 were identified, and their oncological outcomes were collected. Results: A total of 115 patients were identified, among whom 61, 51, and three cases were classified as clinical stage IIIA, IIIB, and IIIC at presentation, respectively. The objective response rate was 61.7% (71/115) after immunochemotherapy. The most frequent surgical procedure was lobectomy, performed in 91 (79.1%) cases, and all patients had microscopic-free margins. Major pathological response (MPR) was observed in 64 (55.7%) patients, among whom 44 (38.3%) achieved a complete pathological response; pathological-confirmed lymph node downstage (cN2-3 to ypN0-1) was described in 73.6% (67/91) of patients with cN2-3 diseases. The median disease-free survival (DFS) of all enrolled patients was 23.6 [95% confidence interval (CI): 15.9-31.3] months, while for patients with residual tumors of more than 10%, the median DFS was 18.1 (95% CI: 12.5-23.8) months. The post-hoc multivariable analysis showed that three [odds ratio (OR), 4.78; 95% CI: 1.17-19.55] and four (OR: 6.50; 95% CI: 1.12-37.54) cycles of neoadjuvant immunochemotherapy were prone to higher MPR rates compared to two cycles in patients that were classified as complete/partial response (CR/PR). However, adding over five cycles was not associated with a higher MPR rate (OR, 0.91; 95% CI: 0.15-5.47). The pretreatment lymphocyte count level (1.89±0.68 vs. 1.59±0.63, P=0.019) and monocyte count level (0.71±0.32 vs. 0.59, P=0.020) were significantly higher in MPR patients compared to non-MPR patients. Conclusions: The present study confirmed a favorable real-world tumor downstage efficacy of neoadjuvant immunochemotherapy in locally advanced NSCLC. Even though CR/PR was achieved, it is still beneficial when extended into 3-4 cycles of neoadjuvant immunochemotherapy.

Spontaneous Ventilation Video-Assisted Thoracoscopic Surgery for Non-small-cell Lung Cancer Patients With Poor Lung Function: Short- and Long-Term Outcomes.

Objective: The goal of this study was to explore the feasibility and safety of spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) for non-small-cell lung cancer (NSCLC) patients with poor lung function. Methods: NSCLC patients with poor lung function who underwent SV-VATS or mechanical ventilation VATS (MV-VATS) from 2011 to 2018 were analyzed. 1:2 Propensity score matching (PSM) was applied, and the short- and long-term outcomes between the SV-VATS group and the MV-VATS group were compared. Results: Anesthesia time (226.18 ± 64.89 min vs. 248.27 ± 76.07 min; P = 0.03), operative time (140.85 ± 76.07 min vs. 163.12 ± 69.37 min; P = 0.01), days of postoperative hospitalization (7.29 ± 3.35 days vs. 8.40 ± 7.89 days; P = 0.04), and days of chest tube use (4.15 ± 2.89 days vs. 5.15 ± 3.54 days; P = 0.01), the number of N1 station lymph node dissection (2.94 ± 3.24 vs. 4.34 ± 4.15; P = 0.005) and systemic immune-inflammation index (3855.43 ± 3618.61 vs. 2908.11 ± 2933.89; P = 0.04) were lower in SV-VATS group. Overall survival and disease-free survival were not significantly different between the two groups (OS: HR 0.66, 95% CI: 0.41-1.07, P = 0.09; DFS: HR 0.78, 95% CI: 0.42-1.45, P = 0.43). Conclusions: Comparable short-term and long-term outcomes indicated that SV-VATS is a feasible and safe method and might be an alternative to MV-VATS when managing NSCLC patients with poor lung function.

Perioperative and long-term outcomes of spontaneous ventilation video-assisted thoracoscopic surgery for non-small cell lung cancer.

BACKGROUND: Spontaneous ventilation video-assisted thoracoscopic surgery (SV-VATS) exhibits dual intraoperative and postoperative advantages for patients with non-small cell lung cancer (NSCLC). However, there is a lack of data regarding its long-term survival superiority over the double-lumen intubated mechanical ventilation video-assisted thoracoscopic surgery (MV-VATS) or thoracotomy. METHODS: A retrospective study was conducted from 2011 to 2018 in the First Affiliated Hospital of Guangzhou Medical University among patients with NSCLC who underwent the SV-VATS or the MV-VATS. Patients receiving the SV-VATS were the study group, and patients receiving the MV-VATS were the control group. Propensity score matching (PSM) was performed to establish 1:1 SV-VATS versus MV-VATS group matching to balance potential baseline confounding factors. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Secondary endpoints were perioperative outcomes. The baseline information of these patients was recorded. The perioperative data and survival data were collected using a combination of electronic data record system and telephone interview. A 1:1:1 SPM was also used to compare the OS in the SV-VATS, the MV-VATS and thoracotomy group by using another database, including patients undergoing thoracotomy and the MV-VATS. RESULTS: For the two-group comparison, after 1:1 PSM, a matched cohort with 400 (200:200) patients was generated. The median follow-up time in this cohort was 4.78 years (IQR, 3.78-6.62 years). The OS (HR =0.567, 95% CI, 0.330 to 0.974, P=0.0498) and the DFS (HR =0.546, 95% CI, 0.346 to 0.863, P=0.013) of the SV-VATS group were significantly better than the MV-VATS group. There were no statistically differences between the SV-VATS and the MV-VATS group on the operative time (158.56±40.09 vs. 172.06±61.75, P=0.200) anesthesia time (247.4±62.49 vs. 256.7±58.52, P=0.528), and intraoperative bleeding volume (78.88±80.25 vs. 109.932±180.86, P=0.092). For the three-group comparison, after 1:1:1 PSM, 582 (194:194:194) patients were included for the comparison of SV-VATS, MV-VATS and thoracotomy. The OS of the SV-VATS group was significantly better than the thoracotomy group (HR =0.379, 95% CI, 0.233 to 0.617, P<0.001). CONCLUSIONS: Invasive NSCLC patients undergoing SV-VATS lobectomy demonstrated better long-term outcomes compared with MV-VATS.