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This was a single-arm, multicenter phase 2 clinical trial (ChiCTR1900021726) involving advanced squamous non-small cell lung cancer (sq-NSCLC) patients undergoing 2 cycles of nab-paclitaxel/carboplatin and sintilimab (anti-PD-1), followed by sintilimab maintenance therapy. The median progression-free survival (PFS) was 11.4 months (95% CI: 6.7-18.1), which met the pre-specified primary endpoint. Secondary endpoints included objective response rate reaching 70.5% and a disease control rate of 93.2%, with a median duration of response of 13.6 months [95% CI: 7.0-not evaluable (NE)]. The median overall survival was 27.2 months (95% CI: 20.2-NE) with treatment-related adverse events grades ≥3 occurring in 10.9% of patients. Predefined exploratory endpoints comprised relationships between biomarkers and treatment efficacy, and the association between circulating tumor DNA (ctDNA) dynamics and PFS. Biomarker analysis revealed that the breast cancer gene 2, BMP/Retinoic Acid Inducible Neural Specific 3, F-box/WD repeat-containing protein 7, tyrosine-protein kinase KIT and retinoblastoma 1 abnormalities led to shorter PFS, while ctDNA negative at baseline or clearance at 2 cycles of treatment was associated with longer PFS (18.1 vs. 4.3 months). Taken together, sintilimab in combination with 2 cycles of nab-paclitaxel/carboplatin treatment produced encouraging PFS and better tolerability as first-line treatment for advanced sq-NSCLC., (© 2024. The Author(s).)

Background: The aims of the study were to evaluate potential differences among first-line treatment for EGFR mutant (m+) non-small cell lung cancer (NSCLC) patients with brain metastasis in China and to identify the factors influencing survival outcomes., Methods: In this retrospective study, 172 EGFRm + patients with advanced NSCLC who received a 1st generation EGFR tyrosine kinase inhibitor (TKI) were divided into 4 groups: A, EGFR-TKI (n = 84); B, EGFR-TKI + pemetrexed + cisplatin/carboplatin chemotherapy (CT) (n = 55); C, EGFR-TKI + bevacizumab (n = 15); and D, EGFR-TKI + pemetrexed + cisplatin/carboplatin CT + bevacizumab (n = 18). Intracranial and extracranial progression-free survival (PFS), the overall survival (OS), objective remission rates (ORRs) and adverse events were analyzed., Results: Intracranial PFS of groups C + D was longer than for groups A + B (18.9 m vs. 11.0 m, P = 0.027). Extracranial PFS were longer in group B in comparison with group A (13.0 m vs. 11.5 m, P = 0.039) and in groups C + D compared to groups A + B (18.9 m vs. 11.9 m, P = 0.008). Median OS in groups A and B were 27.9 m and 24.4 m, respectively, while groups C and D have not yet achieved median OS. Significant difference was found in intracranial ORR between groups A + B vs. C + D (31.0% vs. 65.2%, P = 0.002). Most patients suffered grade 1-2 treatment-related adverse events, which were relieved soon after symptomatic treatment., Conclusions: First-generation EGFR-TKI + bevacizumab treatment outperformed other regimens in EGFRm + NSCLC patients with brain metastasis. The therapy improved the control and delayed progression of intracranial lesions and prolonged survival times., (© 2023. The Author(s).)

Background: Epidermal growth factor receptor (EGFR) mutations are often associated with non-EGFR genetic alterations, which may be a reason for the poor efficacy of EGFR tyrosine kinase inhibitors (TKIs). Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations., Methods: Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant non-EGFR genetic alterations were retrospectively collected. And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy. Demographic, clinical and pathological data were collected, and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression. Survival data were obtained through face-to-face or telephone follow-up. The differences between the two groups in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were investigated., Results: 107 patients were included, including 63 cases in the combination group and 44 cases in the monotherapy group. The ORR were 78% and 50% (P=0.003), and DCR were 97% and 77% (P=0.002), respectively. At a median follow-up of 13.7 mon, a PFS event occurred in 38.1% and 81.8% of patients in the two groups, with median PFS of 18.8 mon and 5.3 mon, respectively (P<0.000,1). Median OS was unreached in the combination group, and 27.8 mon in the monotherapy group (P=0.31). According to the Cox multivariate regression analysis, combination therapy was an independent prognostic factor of PFS CONCLUSIONS: In patients with EGFR-mutant advanced lung adenocarcinoma with concomitant non-EGFR genetic alterations, combination of TKIs and chemotherapy was significantly superior to EGFR-TKIs monotherapy, which should be the preferred treatment option.

Objective: This study aimed to determine whether there is a difference in the efficacy of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) presenting with or without brain metastases., Materials and Methods: Patients with advanced NSCLC treated with nivolumab monotherapy were retrospectively analyzed. They were divided into two cohorts according to the presence or absence of brain metastases. The differences between the two cohorts in objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) and overall survival (OS) were investigated, and the intracranial efficacy, including intracerebral objective response rate (IORR), intracranial disease control rate (IDCR) and intracranial progression-free survival (iPFS), were examined in the brain metastasis (BM) cohort., Results: Seventy-three patients (32 with brain metastases and 41 without) were included. The ORRs of the BM cohort and the non-brain metastasis (non-BM) cohort were 25.0% and 19.5% (p = 0.574), DCRs were 53.1% and 56.1% (p = 0.800), respectively. Their median PFS were 2.8 and 4.9 months (p = 0.204), median DORs were 9.8 and 28.8 months (p = 0.003), and median OS were 14.8 and 20.2 months (p = 0.114), respectively. According to the Cox multivariate regression analysis, BM was not an independent prognostic factor. The IORR and IDCR of the BM cohort were 28.1% and 46.9%, respectively, with a median iPFS of 2.2 months., Conclusions: The efficacy of nivolumab is comparable in patients with NSCLC presenting with and without brain metastases, but the results must be verified in large-scale prospective studies.

Objective: Epidermal growth factor receptor (EGFR) mutation status plays an important role in individual treatment of non-small cell lung cancer.However clinical tissue samples for mutation detection are not always available in advanced NSCLC. Thus an alternative method of EGFR mutation detection is required in NSCLC treatment.Recent studies have associated thyroid transcription factor 1 (TTF-1) with EGFR mutations in lung cancer.In this study, we detected expression of TTF-1 and EGFR mutations in 102 patients with advanced NSCLC and investigated the possibility of TTF-1 as a potential indicator of EGFR status., Methods: Serum and tissue samples were collected from 102 patients with advanced NSCLC including 28 cases of EGFR mutation in 19 exon, 23 cases of EGFR mutation in 21 exon and 51 cases of WT EGFR. Protein levels of TTF-1 in serum were quantified by enzyme-linked immunosorbent assay (ELISA).Levels of TTF-1 in tissues were detected by immunohistochemistry (IHC). SPSS 17 statistical software was used to analyze the data., Results: In the serum the expression of TTF-1 in EGFR 19 and 21 exon MT groups both was higher than that in the WT group(19MT vs 21MT vs WT: 0.092 vs 0.083 vs 0.045; F = 27.653, P < 0.01), and the result of the tissues was the same (19MT vs 21MT vs WT: 0.682 vs 0.644 vs 0.441; F = 47.665, P < 0.01), but no differences between two MT groups were observed (P > 0.05). The ELISA results and the IHC results were consistent (r = 0.87, P < 0.01). The expression of TTF-1 in serum showed a relationship with smoking history (χ² = 4.639, P < 0.05), but not with sex, age, TNM stage and metastasis (P > 0.05)., Conclusions: These results indicated that TTF-1 expression was upregulated in EGFR mutated NSCLC compared to EGFR WT NSCLC. The level of TTF-1 maybe used as a potential marker of EGFR mutation status.