Role of antiangiogenic agents in first-line treatment for advanced NSCLC in the era of immunotherapy.

BACKGROUND & OBJECTIVE: "Anti-angiogenetic drugs plus chemotherapy" (anti-angio-chemo) and "immune checkpoint inhibitors plus chemotherapy" (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy. METHODS: Eligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3-4 toxicity assessment. R-4.3.1 was utilized to perform the analysis. RESULTS: A total of 54 studies with a sample size of 25,046 were finally enrolled. "Atezolizumab + Bevacizumab + Chemotherapy" significantly improved the ORR compared with "Atezolizumab + Chemotherapy" (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27-5.87). The trend also favored "Atezolizumab + Bevacizumab + Chemotherapy" in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39-1.31; HR = 0.94, 95% CI: 0.77-1.16, respectively). In addition, "Pembrolizumab + Chemotherapy" and "Camrelizumab + Chemotherapy" significantly prolonged the PFS compared to "Bevacizumab + Chemotherapy" (HR = 0.65, 95% CI: 0.46-0.92; HR = 0.63, 95% CI: 0.41-0.97; respectively). Meanwhile, "Pembrolizumab + Chemotherapy" and "Sintilimab + Chemotherapy" yielded more OS benefits than "Bevacizumab + Chemotherapy" (HR = 0.69, 95% CI: 0.56-0.83; HR = 0.64, 95%CI: 0.46-0.91; respectively). Scheme between "Atezolizumab + Bevacizumab + Chemotherapy" and "Atezolizumab + Chemotherapy" made no significant difference (OR = 1.18, 95%CI: 0.56-2.42) concerning the rate of grade 3-4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than "Bevacizumab + Chemotherapy" in cost-effectiveness analysis. CONCLUSION: Our results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.

Investigation of the optimal platinum-based regimen in the postoperative adjuvant chemotherapy setting for early-stage resected non-small lung cancer: a Bayesian network meta-analysis.

OBJECTIVE: This study aimed to compare the efficacy and safety of different platinum adjuvant chemotherapy regimens for early-stage resected non-small-cell lung cancer (NSCLC). DESIGN: Systematic review with network meta-analysis of randomised trials. DATA SOURCES: PubMed, EMBASE, The Cochrane Library, Web of Science and Scopus Google Scholar were searched through 12 March 2021. ELIGIBILITY CRITERIA: Eligible randomised controlled trials (RCTs) comparing the postoperative platinum chemotherapy regimen with the observation-controlled group or comparing two platinum chemotherapy regimens head-to-head were included. DATA EXTRACTION AND SYNTHESIS: The primary outcome was the efficacy of adjuvant chemotherapy regimens including relapse-free survival (RFS), overall survival (OS), 2-year, 3-year, 5-year RFS rate and OS rate. The secondary outcome was the rate of grade 3-4 toxicity assessments. Cochrane Handbook (V.5) was used for the risk of bias assessment. Analyses were performed using R software V.4.3.1. RESULTS: 20 RCTs with a sample size of 5483 were enrolled in meta-analysis. The chemotherapy group had a significant RFS and OS advantage compared with the observation group (HR 0.67; 95% CI 0.56 to 0.81, p<0.0001; HR 0.80; 95% CI, 0.73 to 0.88, p<0.0001, respectively). Compared with the observation arm, only the 'cisplatin_vinorelbine' regimen had a significant RFS and OS advantage (HR 0.63; 95% CI 0.43 to 0.87; HR 0.74; 95% CI 0.63 to 0.87, respectively) while the remaining chemotherapy regimens had no significant difference of efficacy compared with the observation group. In terms of the safety of adjuvant chemotherapy, the incidence of haematological toxicities and nausea/vomiting was not significantly higher in the 'cisplatin_vinorelbine' arm than in other chemotherapy group. CONCLUSION: This study summarised the adjuvant cytotoxicity chemotherapy regimens for patients with early-stage resected NSCLC. Our analysis may provide some guiding significance for the clinicians when determining the optimal chemotherapy regimen.

Reducing number of target lesions for RECIST1.1 to predict survivals in patients with advanced non-small-cell lung cancer undergoing anti-PD1/PD-L1 monotherapy.

OBJECTIVES: The Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 provides conventional and standardized response assessment for multiple solid tumors. We investigated the smallest number of target lesions that can be measured without compromising response categorization and survival prediction in patients with advanced non-small-cell lung cancer (aNSCLC) undergoing anti-PD-1/PD-L1 monotherapy. MATERIAL AND METHODS: 125 aNSCLC patients with at least two measurable lesions undergoing PD-1/PD-L1 inhibitor treatment were retrospectively studied. Tumor measurements allowing up to two lesions per organ and five lesions in total were reviewed. Inter-individual agreement and κ values for inter-method concordance on response status were evaluated based on up to five target lesions versus the largest one through four lesions. C-index was calculated to evaluate the prognostic accuracy of response categorization based on the selected number of target lesions for predicting overall survival (OS). Cox regression analysis was conducted for survival analysis. RESULTS: The highly consistent response assignment (99.2%) could be obtained when measuring the largest two lesions versus up to five lesions. Using the largest two through four lesions produced κ values of 0.986, 1.000 and 1.000 for response assessment, values significantly higher than those obtained when measuring the largest single lesion (κ = 0.850). C-index for overall survival (OS) was similar when assessing the largest one through five lesions, ranging from 0.646 to 0.654. Cox regression analyses showed that radiological response significantly predicted OS, irrespective of the number of target lesions selected. CONCLUSIONS: Reducing the number of target lesions does not affect OS prediction in aNSCLC patients treated with anti-PD-1/PD-L1 therapy. Considering the high intra-individual and inter-method concordance, using the largest two lesions in total is proposed to assess response.

Determinants of survival in advanced non-small cell lung cancer patients treated with anti-PD-1/PD-L1 therapy.

BACKGROUND: The present study aimed to investigate the determinant factors of survival in patients with pretreated advanced stage non-small cell lung cancer (NSCLC) who received anti-PD-1/PD-L1 therapy. METHODS: In this observational retrospective study, the clinical profiles and laboratory parameters of patients with NSCLC treated with anti-PD-1/PD-L1 therapy were consecutively collected. Lung Immune Prognostic Index (LIPI) was calculated based on the derived neutrophil-to-lymphocyte ratio (dNLR) and lactate dehydrogenase level (LDH). Modified Glasgow Prognostic Score (mGPS) was calculated based on serum C reactive protein and albumin, and tumor mutation burden (TMB) was calculated using a targeted next-generation sequencing panel based on 422 cancer-relevant genes. The primary and secondary end points were overall survival (OS) and progression-free survival (PFS), respectively. The Cox regression model was used to identify the potential determinant factors of survival benefit. Trained oncologists at Sun Yat-sen University Cancer Center followed all of the participants through visits to doctors' offices or via telephone calls to determine their clinical status. RESULTS: Seventy-three patients were included in our study. With a median follow up time of 637 days, there was a significant difference in PFS between patients with high TMB compared to those with low TMB (3.7 vs. 2.1 months; P=0.004), while no significant difference was found in OS (14.0 vs. 16.4 months; P=0.972). Patients with a good LIPI score had a significantly longer OS compared to patients with a poor LIPI score (19.2 vs. 12.6 months; P=0.010). The median OS in patients with a good and a poor mGPS was 16.8 and 4.3 months, respectively (P=0.029). In multivariate analysis, TMB was found to be significantly associated with PFS (HR, 0.38; 95% CI: 0.21-0.69; P=0.002), while LIPI score was found to be significantly associated with OS (HR, 0.50; 95% CI: 0.28-0.89; P=0.012). CONCLUSIONS: In the present study, LIPI score was a significant determinant of OS in patients with advanced NSCLC who received ICIs; however, TMB was only associated with PFS and not associated with OS.

A case report of small bowel adenocarcinoma with liver metastases: genetic profiling and clinical management.

Small bowel adenocarcinoma (SBA) is a rare cancer. Optimal treatment regimens have not been established for SBA. This is due in part to the low disease incidence and subsequently, the lack of large, properly designed, randomized clinical trials. In this study, we present a case of an advanced small bowel adenocarcinoma patient with a prolonged progression-free survival of more than 3 years. Genetic profiling of this patient was used to predict prognosis and guide clinical management of the disease. The patient was treated with bevacizumab in combination with XELOX based on her genetic background and our experience in treating colorectal cancer. This treatment strategy, which was tolerable and effective, may be considered as a viable therapeutic strategy for the treatment of metastatic SBA.