Efficacy and Safety of First-Line Platinum-Based Doublet Chemotherapy in Advanced Primary Pulmonary Salivary Gland Tumors (PSGTs).

Primary pulmonary salivary gland tumors (PSGT) constitute a rare subtype of non-small cell lung cancer (NSCLC). Currently, no established treatment guidelines exist for advanced PSGT. The efficacy of platinum-based chemotherapy for PSGT within the context of NSCLC remains uncertain. Therefore, we retrospectively collected 37 PSGT patients who underwent first-line platinum-based chemotherapy from 2010 to 2023. Survival analysis, employing the Kaplan-Meier method, and group comparisons via the log rank test were conducted. Our results show that first-line platinum-based chemotherapy demonstrates favorable efficacy and manageable safety in advanced PSGT, with the combination of Paclitaxel + Platinum emerging as a preferred option.

Rechallenge immunotherapy after immune resistance in patients with advanced thymic carcinoma.

BACKGROUNDS: Immunotherapy is effective for patients with advanced thymic carcinoma (TC). However, the effectiveness of rechallenge immunotherapy in patients who are resistant to immunotherapy has not been investigated. METHODS: Thirty-five patients with advanced TC using immunotherapy between 2016 and 2023 at Zhejiang Cancer Hospital, The Second Affiliated Hospital of Nanchang University, and Fujian Cancer Hospital were evaluated in this study. Tumor response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. RESULTS: A total of 35 patients were included in this study. The median PFS (mPFS) for all patients was 5.43 months and the median OS (mOS) was 16 months. After rechallenge immunotherapy, only three patients achieved partial response, resulting in an overall response rate of 16.7%, and nine patients attained stable disease, resulting in a disease control rate of 66.7%. Patients who underwent rechallenge immunotherapy had shorter mPFS compared to chemotherapy (3.53 months vs. 6.00 months, P = 0.041). In addition, the incidence of Grade 3-4 treatment-related adverse events in these patients was 22.2%. CONCLUSION: Rechallenge immunotherapy has poor efficacy in immunotolerant TC patients.

Pyrotinib as a salvage treatment for patients with HER-2 positive advanced lung adenocarcinoma after the progression of afatinib treatment.

BACKGROUND: The efficacy of afatinib or pyrotinib has been demonstrated in HER2-positive advanced non-small cell lung cancer (NSCLC) patients; however, the efficacy of pyrotinib after afatinib progression has yet to be determined. METHOD: Patients with HER2 mutated advanced lung adenocarcinoma administered afatinib or pyrotinib monotherapy were enrolled. Those who received pyrotinib after afatinib were further analyzed to determine the efficacy and safety of pyrotinib after progression on afatinib. Survival curves were plotted with the Kaplan-Meier method. A swimming plot was used to describe the specific treatments. Additionally, patient-derived tumor organoids (PDTOs) were established from HER2-amplified NSCLC patient samples to investigate the antitumor activity of pyrotinib in HER2-amplified tumor cells in vitro. RESULTS: A total of 99 patients were enrolled, 13 of whom were administered pyrotinib after progression on afatinib. No statistical difference in PFS of pyrotinib was observed between patients whether be treated after afatinib progression or not (6.7 months vs. 4.4 months, P = 0.817), thus indicating that progression on afatinib did not affect the efficacy of pyrotinib. Further analysis was conducted on the former patients, which comprising eight patients administered interval chemotherapy after progression on afatinib. Two patients achieved PR after pyrotinib treatment. No independent factors were found to influence the PFS of pyrotinib. PDTOs confirmed the anti-tumor activity of pyrotinib in NSCLC tumor cells with HER2 amplification. CONCLUSIONS: Progression after prior afatinib treatment does not influence the efficacy of pyrotinib treatment. Pyrotinib may be a salvage option for patients with HER2 mutation who have experienced progression on afatinib.

Efficacy and safety analysis of immunotherapy in non-small cell lung cancer patients with MET alterations.

BACKGROUND: Mesenchymal epithelial transition factor (MET) is a rare oncologic driver gene, and information on immunotherapy for non-small cell lung cancer (NSCLC) patients with this driver gene is limited. Here we evaluate the efficacy and safety of immune checkpoint inhibitors (ICI) under different therapeutic regimen for NSCLC patients with MET alterations. METHODS: From June 2019 to December 2023, we assessed the efficacy and toxicity of ICIs in 42 NSCLC patients with MET alterations. Survival curves were plotted using the Kaplan-Meier method and the Cox proportional hazards model applied for univariate and multivariate analyses. We assessed the size of target lesion according to RECIST v1.1, and objective response rate (ORR) was defined as the sum of complete response (CR) and partial response (PR), disease control rate (DCR) as the sum of CR, PR, and disease stable. RESULTS: A total of 42 NSCLC patients with MET alterations were included in this retrospective study, 10 was MET 14 skipping mutation and 32 was MET amplification. The ORR for ICI treatment was 30.95% and the DCR was 71.43%. Median progression-free survival (mPFS) and median overall survival (OS) were 4.40 and 13.97 months, respectively. There exists statistical differences between the mPFS of ICI monotherapy and combine ICI therapy (2.8 vs 7.8 months, p = 0.022). The incidence of drug-related adverse reactions was 47.62%, mainly bone marrow suppression (14.28%), immune-related pneumonia (7.14%), and liver function impairment (7.14%), and six patients (14.28%) experiencing grade 3 or above adverse events. CONCLUSION: NSCLC patients with MET alterations can benefit from immunotherapy, especially the patients treated by combined ICI therapy. However, special attention should be paid to the occurrence of grade 3/4 adverse reactions while using the combined ICI therapy.

Clinical characteristics and prognostic implications of immune-related hepatitis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors: a retrospective study.

Background: With the widespread use of immune checkpoint inhibitors (ICIs), patients inevitably experience immune-related adverse events (irAEs). Therefore, the study was conducted on the clinical characteristics and outcomes of patients with non-small cell lung cancer (NSCLC) with immune-related hepatitis (ir-hepatitis). Methods: We identified patients with advanced NSCLC who developed ir-hepatitis after immunotherapy between June 2016 and December 2022. Their irAEs were categorized according to the Common Terminology Criteria for Adverse Events version 4.03 (CTCAE 4.03). Kaplan-Meier curves and log-rank tests were used to analyze survival. Results: A total of 35 patients were enrolled in the study. The numbers of mild (grade 1-2) and severe (grade 3-4) ir-hepatitis cases were 13 (grade 1, 3; grade 2, 10) and 22 (grade 3, 17; grade 4, 5), respectively. The median onset time of ir-hepatitis was 1.6 months. The median progression-free survival (mPFS) was 8.3 months. PFS differed between patients with early ir-hepatitis developing within two treatment cycles and those with ir-hepatitis developing more than two treatment cycles (5.5 vs. 12.7 months, P=0.004). Patients with severe rather than mild ir-hepatitis tended to poorer PFS survival (5.8 vs. 11.2 months, P=0.130). The appearance of ir-hepatitis within two treatment cycles (P=0.002) and higher severity grades of ir-hepatitis (P=0.005) were independent risk factors for PFS. Conclusions: Early and severe ir-hepatitis are associated with worse survival benefits, which still required more basic and perspective studies.

Comparison of the efficacy and safety of anlotinib monotherapy or anlotinib plus immune checkpoint inhibitor for advanced small cell lung cancer with brain metastases.

BACKGROUND: Anlotinib, as a salvage treatment for patients after failure of third-line or later-line treatments for small cell lung cancer (SCLC), has shown efficacy in patients with brain metastases (BMs). However, the efficacy and safety of anlotinib alone or in combination with immunotherapy for SCLC with BMs remain unclear. METHOD: Patients treated with anlotinib alone or in combination with an immune checkpoint inhibitor (ICI) at the Zhejiang Cancer Hospital between April 2019 and February 2023 were identified. Kaplan-Meier curves were used to describe the progression-free survival (PFS) and intracranial PFS (iPFS). A waterfall diagram was used to indicate changes in intracranial lesions. RESULTS: A total of 48 patients were included; 29 received anlotinib alone, and 19 were administered anlotinib plus ICI. Combination therapy, compared with anlotinib, was associated with significantly longer PFS and iPFS (PFS: 8.1 months vs. 2.5 months, P < 0.001; iPFS: 8.1 months vs. 2.5 months, P = 0.004). Similar results were observed in patients with multiple BMs (PFS: 8.1 months vs. 1.9 months, P = 0.001; iPFS: 8.1 months vs. 1.9 months, P = 0.002). After third-line or later-line treatments, patients treated with ICI plus anlotinib also achieved significant PFS and iPFS benefits (PFS: 8.4 months vs. 2.1 months, P < 0.001; iPFS: 9.2 months vs. 2.1 months, P = 0.002). No new or severe adverse events were observed with combination therapy. CONCLUSION: The combination of anlotinib and ICI has promising intracranial and extracranial efficacy with tolerable toxicity, and may be a therapeutic option for SCLC patients with BMs.