ABSTRACT Objective Malignant mesothelioma (MM) is a rare malignant tumor. To explore the clinicopathological characteristics and efficacy of Chinese population with MM in the real‐world. Methods Two hundred and forty‐eight patients diagnosed with MM between September 2007 and August 2024 from three large medical centers (Beijing Hospital, Peking University Cancer Hospital, and Chinese Academy of Medical Sciences Cancer Hospital) were retrospectively analyzed. Kaplan–Meier and Cox regression were performed. Breast cancer gene 1‐associated protein 1 ( BAP1 ) status was evaluated. Results Chinese population with MM had a lower diagnostic age, higher proportion of youth and female, more advanced stage and lower expression of characteristic markers. The median progression‐free survival (mPFS) and median overall survival (mOS) were 8.90 and 25.60 months for the first‐line treatment, and 3.28 and 19.50 months for the second‐line. The first‐line immunotherapy provided a relatively higher objective response rate (33.3% vs. 20.5%, p = 0.402) and a trend to prolong mPFS (12.10 vs. 9.20 months, p = 0.345) and mOS (NA vs. 23.90, p = 0.185) compared with chemotherapy. Bevacizumab combined with chemotherapy relatively prolonged mPFS (10.47 vs. 7.93 months, p = 0.074) and mOS (31.30 vs. 23.20 months, p = 0.673) than chemotherapy alone. Carboplatin relatively improved mPFS than cisplatin (10.87 vs. 8.87 months, p = 0.185). Age and histologic type were predictors for PFS, and gender, histologic subtype, and CK5/6 were prognosis factors for OS. Briefly, 17.78% patients existed BAP1 deletions and correlated with OS benefit. Conclusion Chinese population with MM present unique clinicopathologic characteristics and could benefit from the first‐line immunotherapy and bevacizumab combined with chemotherapy. Gender, histologic subtype, and CK5/6 are prognosis factors for OS. BAP1 deletions correlate with OS benefit.

AbstractObjectivesTo evaluate the efficacy and safety of programmed cell death 1 (PD‐1)/programmed cell death ligand 1 (PD‐L1) inhibitors in the treatment of extensive‐stage small‐cell lung cancer (ES‐SCLC), we conducted a systematic review and meta‐analysis that included randomized controlled trials (RCTs) and real‐world studies (RWS).MethodsBy scanning PubMed, Web of science, Embase, and other relevant clinical information public databases, nine RCTs and eight RWSs involving 5205 patients were included in the study. We directly compared the differences between chemotherapy and PD‐1/PD‐L1 inhibitors plus chemotherapy, and determined the optimal treatment strategy through network meta‐analysis (NMA).ResultsCompared to chemotherapy, the addition of PD‐1/PD‐L1 inhibitors significantly improves the overall survival (OS), progression‐free survival (PFS), and objective response rate (ORR) in SCLC patients. Regarding safety, both RCTs and RWSs indicated no significant difference in grade 3–4 adverse events between chemotherapy and chemoimmunotherapy. NMA showed serplulimab plus chemotherapy (Serp_Chemo) appears to provide the best OS, PFS, and ORR benefit, while nivolumab plus chemotherapy shows higher toxicity than other regimens. In subgroup analysis, for elderly patients (age ≥65) and non‐elderly (age <65) patients, the most promising quality regimens for achieving better OS extension are atezolizumab plus chemotherapy (Atez_Chemo) and Serp_Chemo, respectively. For patients with PD‐L1 ≥ 1% and lactate dehydrogenase (LDH) > upper limit of normal (ULN), there is no apparent OS benefit from immune therapy.ConclusionsIn ES‐SCLC treatment, adding PD‐1/PD‐L1 inhibitors to standard chemotherapy improves OS, PFS, and ORR, with Serp_Chemo shows the most promise. Atez_Chemo and Serp_Chemo provided better survival for elderly and non‐elderly patients, respectively.

Abstract Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first‐line treatment only results in 10‐month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD‐1/PD‐L1 and CTLA‐4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG‐3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.

Objective:To investigate the efficacy and adverse reactions of immunotherapy in elderly patients(≥65 years old)with lung squamous cell carcinoma(LUSC)in Chinese population of real world.Methods:A total of 113 elderly LUSC patients(age ≥65 years old)underwent pathological diagnosis were involved from January 2018 to January 2022.To compare the efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line and second-line treatment.44 patients received surgical or minimally invasive treatment, and 69 patients received first-line medical treatment, including 27 patients in chemotherapy group, 24 patients in combined chemotherapy group, and 11 patients in single drug immunization group.7 cases in targeted therapy group.Twenty-eight patients received second-line medical treatment, including 8 patients in chemotherapy group, 11 patients in combined immunochemotherapy(combined group), 4 patients in single drug immunotherapy group, and 5 patients in targeted therapy group.The therapeutic effects and adverse reactions were compared between the first-line and second-line treatments.The expression of programmed death-ligand 1(PD-L1)and tumor mutational burden(TMB)were evaluated.Response evaluation criteria in solid tumors(RECIST)version 1.1 was used to evaluate the efficacy, and common terminology criteria for adverse events(CTCAE)version 4.03 was used to evaluate immune-related adverse.Kaplan-meier and log-rank test was performed.Cox regression was used in prognostic analysis.Results:The total effective rate in the first-line combination group was 73.7%(14/19), higher than that in the chemotherapy group(24.0%, 6/25), and the difference was statistically significant( χ2=10.748, P<0.01). Median progression-free survival(mPFS)was longer in the first-line combination group, the immunization group, and the chemotherapy group, and the median overall survival(mOS)was longer in the combination group, but the differences were not statistically significant(all P<0.05); mOS in the second-line combined group were longer than those in the chemotherapy group, both P<0.01). Elderly patients with lung squamous cell carcinoma had high PD-L1 positive rate(≥1%)and high TMB expression rate(≥9 mut/Mb), 81.6%(31/38)and 57.4%(31/54), respectively.mPFS in the PD-L1 positive group(≥1%)was better than that in the PD-L1 negative group(5.10 months vs.0.93 months, P<0.05). Among PD-L1 positive patients, mPFS in the second-line combination group was better than that in the chemotherapy group(7.33 months vs.2.77 months, P<0.05). mPFS and mOS time were not related to TMB expression.The overall incidence of immune-related adverse reactions was 62.0%(31/50), and 26.0%(13/50)with grade 3 or above.The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. Conclusions:Immunology combined with chemotherapy increased objective response rate, mPFS and mOS of elderly patients with LUSC group in first-line therapy compared with chemotherapy.In second-line treatment, the mOS was significantly prolonged in both combination therapy and mono-immunotherapy, and the combination therapy exhibited no benefit in OS compared with monotherapy.The adverse effects of immunology in elderly patients with LUSC were controllable.

BACKGROUND:Immune checkpoint inhibitors (ICIs) improved survival of partial patients with lung squamous cell carcinoma (LUSC). However, it was still insufficient of data in older patients. This study aimed to investigate the efficacy and toxicity of immunotherapy in patients with LUSC in Chinese population of real world. METHODS:A total of 185 LUSC patients underwent pathological diagnosis were involved from January 2018 to January 2022. Patients were divided into elderly group (age ≥70 years) and younger group (age <70 years). The efficacy of mono-immunotherapy or combined with chemotherapy to chemotherapy in first-line treatment was compared. The expression of programmed cell death ligand 1 (PD-L1) and tumor mutational burden (TMB) were evaluated. Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was used to evaluate the efficacy, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 was used to evaluate immune-related adverse. Kaplan-Meier and Log-rank test was performed. Cox regression was used in prognostic analysis. RESULTS:Combined therapy acquired significantly higher overall response rate (ORR) compared with chemotherapy alone in elderly group (P<0.05), and also in younger group, despite the difference was not significant (P>0.05). The median progression-free survival (mPFS) and median overall survival (mOS) in elderly group were similar with younger group (P>0.05). Both combined group and immunology alone demonstrated prolonged mPFS in first-line compared with chemotherapy in elderly group. And combined group demonstrated significantly prolonged mPFS compared with chemotherapy in younger group (P<0.01). There was no difference of mOS between different regimes in two groups. Elderly LUSC patients had higher PD-L1 positive rate (≥1%) and similar TMB compared with younger group. There was no relationship between mPFS and mOS with the expression of PD-L1 and TMB. Immunology combined with chemotherapy demonstrated better mPFS compared to chemotherapy in first-line therapy with TMB-High (P<0.05), and inferior mPFS with TMB-Low despite the difference was not significant (P>0.05). Cox regression model demonstrated that clinical stage was an independent predictor and prognostic factor. The incidence of immune-related adverse was 58.0% (51/88) and grade 3 or above 25.0% (22/88). The most common grade 3 adverse events were rash, immune-associated pneumonia, and fatigue. CONCLUSIONS:Immunology combined with chemotherapy increased ORR, mPFS and mOS of Chinese patients with LUSC in first-line therapy compared with chemotherapy. There was no difference of efficacy and adverse effects rate between elderly group and younger group. The adverse effects of immunology in elderly patients with LUSC were controllable.