A pivotal bridging study of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer.

This single-arm, multi-center clinical trial aimed to evaluate the safety, tolerability, DLT, recommended dose (RD), preliminary efficacy, and pharmacokinetics (PK) characteristics of lurbinectedin, a selective inhibitor of oncogenic transcription, in Chinese patients with advanced solid tumors, including relapsed SCLC. Patients with advanced solid tumors were recruited in the dose-escalation stage and received lurbinectedin in a 3 + 3 design (two cohorts: 2.5 mg/m2 and 3.2 mg/m2, IV, q3wk). The RD was expanded in the following dose-expansion stage, including relapsed SCLC patients after first-line platinum-based chemotherapy. The primary endpoints included safety profile, tolerability, DLT, RD, and preliminary efficacy profile, while the secondary endpoints included PK characteristics. In the dose-escalation stage, ten patients were included, while one patient had DLT in the 3.2 mg/m2 cohort, which was also the RD for the dose-expansion stage. At cutoff (May 31, 2022), 22 SCLC patients were treated in the ongoing dose-expansion stage, and the median follow-up was 8.1 months (range 3.0-11.7). The most common grade ≥ 3 treatment-related adverse events (TRAEs) included neutropenia (77.3%), leukopenia (63.6%), thrombocytopenia (40.9%), anemia (18.2%), and ALT increased (18.2%). The most common severe adverse events (SAEs) included neutropenia (27.3%), leukopenia (22.7%), thrombocytopenia (18.2%), and vomiting (9.1%). No treatment-related deaths occurred. The Independent Review Committee (IRC)-assessed ORR was 45.5% (95% CI 26.9-65.3). Lurbinectedin at the RD (3.2 mg/m2) showed manageable safety and acceptable tolerability in Chinese patients with advanced solid tumors, and demonstrates promising efficacy in Chinese patients with SCLC as second-line therapy.Trial registration: This study was registered with ClinicalTrials.gov NCT04638491, 20/11/2020.

A randomized, double-blind, parallel-group phase I study comparing the pharmacokinetics, safety, and immunogenicity of LY01008, a candidate bevacizumab biosimilar, with its reference product Avastin® in healthy Chinese male subjects.

BACKGROUND: Bevacizumab, an inhibitor of angiogenesis, has been approved in several anti-cancer therapies. This study compared the pharmacokinetic (PK) profiles, safety, and immunogenicity of a bevacizumab biosimilar, LY01008, with those of European Union - approved bevacizumab (Avastin®) in healthy Chinese males. RESEARCH DESIGN AND METHODS: In this double-blind, open-label, parallel-group study, healthy Chinese male subjects were randomized 1:1 to receive either LY01008 or Avastin® 3 mg/kg intravenously. Primary study endpoints were PK parameters such as the area under the concentration-time curve (AUC) from time zero to infinity (AUC0-∞), AUC from time zero to last quantifiable concentration (AUC0-t), and maximum serum concentration (Cmax). Secondary study endpoints included safety, tolerability, and immunogenicity. RESULTS: One hundred and twelve subjects were randomized to receive LY01008 (n = 56) or Avastin® (n = 56). The 90% CIs of the GMRs of AUC0-t, AUC0-∞, and Cmax of LY01008 to Avastin® were all within the bioequivalence margin. Other PK parameters, safety, and immunogenicity profiles were comparable across the two treatment groups. CONCLUSIONS: This study demonstrated equivalent PK, comparable safety, and similar immunogenicity of LY01008 to Avastin® in healthy subjects, thus paving the way for further clinical evaluation. TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT05110118).

[A Case Report on Successful Third Challenge to the Pemetrexed-based Regimen for Advanced Non-small Cell Lung Cancer].

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, with a 5-year survival rate of less than 15%-19%, and more than 80% of the patients with lung cancer have progressed to advanced stage (Stage IIIb-IV) when they are clearly diagnosed. The comprehensive treatment mainly based on chemotherapy as the primary form is now considered as the major therapy method for advanced NSCLC without actionable driver gene mutations. Pemetrexed plus platinum doublet as well as single-agent pemetrexed are respectively the first-line major regimens recommended by guidelines and the second-line optional regimens. Yet the third-line treatment or beyond in advanced NSCLC is not evidence-based but conducted based on patients' previous medications, which is one of the most commonly used clinical methods. As pemetrexed is a multi-target chemotherapy drug with high efficiency but low toxicity, pemetrexed re-challenge strategy in advanced NSCLC is also a reasonable choice. We report one effective individual case that adopted pemetrexed re-challenge strategy in advanced NSCLC for three times, and at the same time conduct the relevant literature review.

Influence of body mass index on the therapeutic efficacy of gemcitabine plus cisplatin and overall survival in lung squamous cell carcinoma.

BACKGROUND: Gemcitabine plus cisplatin (GP) is commonly used to treat lung squamous cell carcinoma (SCC); however, it is not clear which subgroup of lung SCC patients could benefit most from GP treatment. We explored the predictive factors in lung SCC patient cohorts. METHODS: Seventy-eight lung SCC patients treated with a first-line GP regimen were enrolled in this retrospective cohort study. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Classification tree models were used to explore the risk factors for PFS and OS in these patients. RESULTS: The median PFS and OS in SCC patients treated with a GP regimen were 6.0 and 13.6 months, respectively. Three terminal subgroups were formed for both PFS and OS. The subgroup with a body mass index (BMI) > 23.94 kg/m2 and aged ≤ 54.5 had the longest PFS (9.0 months); the subgroup with a BMI < 23.94 kg/m2 and aged ≤ 54.5 had the shortest PFS (4.05 months). Patients with an objective response (partial or complete response) to treatment had the longest OS (20.0 months), while patients with a BMI ≤ 26.92 kg/m2 and stable or progressive disease as the best response had the shortest OS (11.2 months). CONCLUSIONS: BMI and age may be predictors of PFS in lung SCC patients who receive GP treatment. BMI and best response to GP treatment predicts OS in such patients. Patients' clinical pathological characteristics may be used to predict the therapeutic efficacy of chemotherapy and survival.

Survival difference between EGFR Del19 and L858R mutant advanced non-small cell lung cancer patients receiving gefitinib: a propensity score matching analysis.

OBJECTIVE: Although superior clinical benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in the treatment of advanced non-small-cell lung cancer (NSCLC) had been reported, the survival difference between exon 19 deletion (Del19) and exon 21 Leu858Arg substitution (L858R) remains controversial. The purpose of this study is to investigate the differences in progression-free survival (PFS) and overall survival (OS) between different EGFR mutant subtypes among advanced NSCLC patients receiving gefitinib. METHODS: There were 204 advanced NSCLC patients with EGFR mutations treated with gefitinib were enrolled in this retrospective cohort study. Patients were divided into the EGFR Del19 group and the L858R mutated group according to their mutant subtype. Propensity score matching (PSM) was conducted by using a nearest-neighbor algorithm (1:1) to adjust for demographical and clinical covariates. Survival curves were constructed with the Kaplan-Meier method and compared by using the log-rank test. RESULTS: The PFS in Del19 group was similar to that in the L858R group [before PSM 8.6 vs. 7.2 months, P=0.072; after PSM 7.3 vs. 7.2 months, P=0.155]. No differences were detected in OS between the L858R and the Del19 group (before PSM 17.8 vs. 13.1 months, P=0.253; after PSM 16.9 vs. 13.1 months, P=0.339). The Del19 group was significantly younger compared with the L858R mutation group in age (P=0.015). CONCLUSIONS: No significant difference was found in the PFS or OS between the Del19 and L858R mutant NSCLC patients receiving gefitinib. The age gap might contribute to the survival differences between Del19 and L858R groups. PSM is of important value to the elimination of potential bias.

[Clinical Efficacy of Crizotinib in Treatment of Patients with Advanced NSCLC].

BACKGROUND AND OBJECTIVE: Crizotinib was developed in recent years based on targets of anaplastic lymphoma kinase (ALK) fusion genes. The aim of this study is to explore the efficacy of crizotinib in treatment of non-small cell lung cancer (NSCLC) with ALK/ROS1 rearrangement. METHODS: Retrospective analysis of 40 patients with ALK/ROS1-positive NSCLC, who received treatment in Beijing Cancer Hospital during the period from Jun. 2013 to Dec. 2014. RESULTS: Among these cases, 39 were adenocarcinoma and adenosquamous carcinoma, with characters involving signet-ring cell carcinoma, polypoid adenocarcinoma, acini and papillary adenocarcinoma. The median age was 49.5 years old, with the overall response rate of 62.5% and disease control rate of 95.0%. Of all the cases, median follow-up was 14.6 months and median PFS 7.5 months; median OS has not been reached; the one-year survival rate was 77.4%. The median PFS and OS of patients receiving first and second-line treatment tend to be longer than those who received post-second line treatment, but with no statistical significance (PFS: 9 mo vs 6 mo, P=0.06; OS: 21.5 mo vs 14.6 mo, P=0.12). Twenty patients who experienced progression in brain metastases. After experiencing progression, the patients receiving 2nd/3rd generation ALK-TKI treatment showed efficacy of disease control and survival. The adverse events include gastrointestinal reaction, transaminase elevation, and distinctive visual abnormalities, etc. CONCLUSION: The clinical features, efficacy, and adverse events of crizotinib in the treatment of the 40 patients with ALK/ROS1-positive NSCLC are similar to the data from the previous reports. The most common site of progression was brain metastases. The treatment of crizotinib-resistant patients using 2nd/3rd generation ALK-TKI could delay progression.

Hyperthermic intraperitoneal chemotherapy plus high-frequency diathermic therapy followed by intravenous chemotherapy versus intravenous chemotherapy alone for postoperative adjuvant treatment of gastrointestinal cancer: a comparative research study.

PURPOSE: To evaluate the therapeutic efficacy and toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) plus high-frequency diathermic therapy (HFDT) followed by intravenous chemotherapy vs intravenous chemotherapy alone for adjuvant treatment of postoperative gastrointestinal neoplasms. METHODS: Fifty-two gastrointestinal carcinoma patients who were radically operated were enrolled and divided into the treatment group and the control group. In the treatment group, 25 patients were treated with combination of HIPEC+HFDT and subsequent intravenous chemotherapy, while in the control group 27 patients received intravenous chemotherapy alone. Post-therapeutic complications and adverse reactions, time to progression (TTP) and overall survival (OS) were compared between these two groups. RESULTS: Difference in toxic reactions between the two groups was not statistically significant (p>0.05). Postoperative progression- free survival (PFS) rate at 12 and 40 months after radical surgery was 72.0 and 54.0% respectively in the treatment group, and 65.8 and 11.5% respectively in the control group (p=0.108). TTP was statistically significantly longer in the treatment group than in the control group (median TTP 40.1 vs 18.5 months, p=0.027). Postoperative OS at 12 and 20 months after radical surgery was 88.0 and 78.0% respectively in the treatment group and 92.6 and 72.7% in the control group, without significant difference. CONCLUSION: After radical surgery, combination of HIPEC+HFDT and subsequent intravenous chemotherapy brings about superior PFS compared with intravenous adjuvant chemotherapy alone, while having no more complications and adverse reactions.