Efficacy of third-line pemetrexed monotherapy versus pemetrexed combination with bevacizumab in patients with advanced EGFR mutation-positive lung adenocarcinoma.

OBJECTIVE: The purposes of this study were to observe the effects of different treatment strategies, including third-line pemetrexed alone versus its combination with bevacizumab, in patients with advanced epidermal growth factor receptor (EGFR) mutation-positive lung adenocarcinoma, and to analyze the effects of the different medication orders of first- and second-line drugs on third-line efficacy. PATIENTS AND METHODS: One hundred and sixteen cases of patients with EGFR-positive lung adenocarcinoma who had received third-line pemetrexed alone or in combination with bevacizumab between March 2010 and March 2014 at Guangzhou Institute of Respiratory Diseases, the First Affiliated Hospital of Guangzhou Medical University were analyzed retrospectively. Additionally, all the patients were treated with first-line gemcitabine and cisplatin (GP) chemotherapy and second-line EGFR tyrosine kinase inhibitor (TKI) or with first-line EGFR-TKI and second-line GP chemotherapy. RESULTS: The median survival of 61 cases with third-line pemetrexed monotherapy was 36.22 months, the median survival time of 55 cases with third-line pemetrexed plus bevacizumab was 38.76 months, and there was a significant difference in survival time between the two groups (P=0.04). Subgroup analysis revealed that among the 55 cases with third-line bevacizumab plus pemetrexed treatment, the median survival of 29 patients with first-line GP and second-line EGFR-TKI was 42.80 months, while the median survival of 26 patients with first-line EGFR-TKI and second-line GP was only 34.46 months; additionally, there was a significant difference in the survival time between the two subgroups (P=0.001). Among 61 cases with third-line pemetrexed treatment, the median survival of 34 patients with first-line GP and second-line EGFR-TKI was 38.72 months, while the median survival of 27 patients with first-line EGFR-TKI and second-line GP was only 32.94 months; the survival time of the two subgroups was significantly different (P=0.001). CONCLUSIONS: Regardless of the order of the first- and second-line chemotherapy and TKI therapy, the pemetrexed plus bevacizumab regimen was superior to the pemetrexed monotherapy as the third-line therapy in patients with advanced EGFR-positive lung adenocarcinoma. However, this strategy is worth further investigation in prospective studies.

Anlotinib Plus S-1 for Patients with EGFR Mutation-Negative Advanced Squamous Cell Lung Cancer with PS Scores of 2-3 After Progression of Second-Line or Later-Line Treatment.

OBJECTIVE: The study aimed to analyze the efficacy and safety of combination regimen of anlotinib and S-1 for Chinese patients with EGFR mutation-negative advanced squamous cell lung cancer (SqCLC) with poor performance status (PS,2-3) after progression of second-line or later-line chemotherapy. METHODS: Clinical data of 70 SqCLC patients with PS scores of 2-3 treated in the First Affiliated Hospital of Guangzhou Medical University between January 1, 2018 to September 31, 2019 who failed second- or more-line treatment were analysed retrospectively. The patients were divided into two treatment groups: anlotinib (12mg) plus S-1 (25mg) combination group and anlotinib (12mg) monotherapy group. The efficacy and adverse reactions of the two groups were compared. RESULTS: In terms of the short-term efficacy, there were no significant differences in objective response rate (ORR) (20.0% vs 10.0%, p = 0.464) and disease control rate (DCR) (75.0% vs 60.0%, p = 0.181) between the two groups. As for the long-term efficacy, there was no significant difference in progression-free survival (PFS) between the two groups (3.87±0.29 months vs 3.00±0.24 months, p=0. 11). The overall survival (OS) of patients in the combination group was longer than S1 group (8.07±0.56 months vs 6.17±0.42 months, p=0.022). CONCLUSION: Advanced SqCLC patients with higher PS scores still benefit from anlotinib and S-1 combination regimen, even after they failed second-line or later-line systemic treatment.

Clinical features, treatment, and survival outcome of primary pulmonary NUT midline carcinoma.

OBJECTIVE: NUT midline carcinoma (NMC), a rare type of squamous cell carcinoma, is genetically characterised by NUT midline carcinoma family member 1 (NUTM1) gene rearrangement. NMC can arise from the lungs; however, there is no standard for the management of primary pulmonary NMC. This study aimed to confirm the clinical features and report the treatments, especially with immune checkpoint inhibitors (ICIs), and outcomes of patients with primary pulmonary NMC. METHODS: A retrospective review of patients with primary pulmonary NMC was performed in the First Affiliated Hospital of Guangzhou Medical University between January 2015 and December 2018. Clinical manifestations as well as radiographic and pathological findings were recorded. Whole-exome sequencing (WES), a predictor for ICI response, was used to determine the tumour mutational burden (TMB). Treatments, especially by immune checkpoint blockade, and patient survival were analysed. RESULTS: Seven patients with primary pulmonary mass (four men and three women) with a mean age of 42 years (range, 23-74) who were diagnosed with NMC according to NUT immunohistochemistry staining were included for analysis. One patient had a rare fusion of CHRM5-NUTM1 by tumour sequencing. A wide range of TMB (1.75-73.81 mutations/Mbp) was observed. The initial treatments included chemotherapy (5/7, 71.4%), surgery (1/7, 14.3%), and radiotherapy (1/7, 14.3%). Five patients (5/7, 71.4%) received ICIs (programmed cell death protein 1 [PD1]/programmed cell death ligand 1 [PDL1] monoclonal antibody) as second- or higher-line treatments. The median overall survival (OS) was 4.1 months (range, 1.5-26.7 months). CONCLUSIONS: Patients with primary pulmonary NMC have a poor prognosis and chemotherapy is often preferred. Checkpoint immunotherapy is a good option as the second- or higher-line treatment. TMB seems to be not associated with OS.

Development and validation of a model to predict tyrosine kinase inhibitor-sensitive EGFR mutations of non-small cell lung cancer based on multi-institutional data.

BACKGROUND: Non-small cell lung cancer (NSCLC) with different EGFR mutation types shows distinct sensitivity to tyrosine kinase inhibitors (TKIs). This study developed a patho-clinical profile-based prediction model of TKI-sensitive EGFR mutations. METHODS: The records of 1121 Chinese patients diagnosed with NSCLC from November 2008 to October 2014 (the development set) were reviewed. Multivariate logistic regression was conducted to identify any association between potential predictors and the classic sensitive EGFR mutations (exon 19 deletion and exon 21 L858R point mutation). A prediction index was created by assigning weighted scores to each factor proportional to a regression coefficient. Validation was made in an independent cohort consisting of 864 patients who were consecutively enrolled between November 2014 and January 2017 (the validation set). RESULTS: Seven independent predictors were identified: gender (female vs. male), adenocarcinoma (yes vs. no), smoking history (no vs. yes), N stage (N+ vs. N0), M stage (M1 vs. M0), brain metastasis (yes vs. no), and elevated Cyfra 21-1 (no vs. yes). Each was assigned a number of points. In the validation set, the area under curve of the prediction index appeared as 0.698 (95% confidence interval 0.663-0.733). The sensitivity, specificity, positive and negative predictive values, and concordance were 95.0%, 32.3%, 61.4%, 85.1%, and 65.6%, respectively. CONCLUSION: We developed a patho-clinical profile-based model for predicting TKI-sensitive EGFR mutations. Our model may represent a noninvasive, economical choice for clinicians to inform TKI therapy.

[Expansion of erythroid progenitors and CD34+ cells by umbilical cord blood mononuclear cells].

Cord blood represents a large source of hematopoietic stem/progenitor cells. It can be induced to proliferate directly into erythroid progenitors in a appropriate ex vivo culture condition, then to generate mature red blood cells after injection into the body. The combination of Flt3 ligand, TPO, SCF and EPO is ideal for cord blood MNC to proliferate into erythroid progenitors. This study was aimed to evaluate the effect of FL, SCF and TPO on CD34(+) expansion. and to investigate influence of the cytokine combination on the proliferation of the CD34(+) cells. Mononuclear cells (MNC) were cultured in serum-free liquid culture system. Experiments were divided into 3 groups. In the group A as control no cytokines were added in the culture system; in the group B the cells cultured with SCF + FL + TPO + EPO + IGF-1; in the group C the cells were cultured with SCF + FL + TPO. EPO and IGF-1 were added at day 6. Part of the renewed MNCs and colony-forming units were counted, the proportion of CD34(+), CD34(+) CD71(+), CD71(+) GPA(+) cells was detected by FACS. The result showed that after 10 days, the the total cord blood cells increased 6.89-folds in group B and 3.06-folds in group C (P < 0.05). The CD34(+) cells increased 4.83-folds in group B and 2.47-folds in group C (P < 0.05). The colony-forming cells (CFCs) increased 4.3-folds in group B and 2.5-folds in group C (P < 0.05). Erythroid progenitors (BFU-E) and CFU-E increased 5.4-folds in group B and 3.1-folds in group C (P < 0.05). The CD34(+)CD71(+) cells increased 8.72-folds in group B and 3.37-folds in group C (P < 0.05). The CD71(+) GPA(+) cells increased 53.4-folds in group B and 30.29-folds in group C. They were different at any time point (P < 0.05). It is concluded that in the group with FL + SCF + TPO, CD34(+) cells and CFC can greatly be expanded from cord blood MNC in the serum-free culture system. In the group with FL + SCF + TPO + EPO + IGF-1, erythroid progenitors can greatly be expanded in the serum-free culture system, supplying EPO at day 0 was better than supplying at day 6. Since the largest number of colony-forming cells such as BFU-E and CFU-E were gained in the TPO + SCF + FL + EPO + IGF-1 group at day 10, the harvest time after cultivation in vitro should be selected at day 10.