Addition of thoracic radiotherapy to a PD-L1 inhibitor plus chemotherapy regimen delays brain metastasis onset in extensive-stage small cell lung cancer patients without baseline brain metastasis.

With the application of immune checkpoint inhibitors (ICIs) and the discovery of the synergistic effect of radiotherapy and immunotherapy, the intracranial benefit of thoracic radiotherapy (TRT) is receiving signiffcant clinical attention. The purpose of this study was to analyze the cranial benefits of ICIs and TRT in patients with extensive-stage small cell lung cancer (ES-SCLC) without baseline brain metastases (BMs). From August 2019 to August 2022, data from patients diagnosed with ES-SCLC without baseline BMs were retroactively recorded. The Kaplan‒Meier method was used to calculate overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and the differences between the treatment groups were compared with the log-rank test. Risk factors associated with OS were analyzed via the Cox regression model. A total of 216 patients were included, with a median follow-up of 24.73 months. Among these patients, 137 (63.4%) received first-line ICIs combined with chemotherapy (ChT), including 32 patients treated with anti-programmed death 1 antibody (αPD-1) and 105 patients treated with anti-programmed death-ligand 1 antibody (αPD-L1), and 79 patients (36.6%) received first-line ChT alone. Compared with the ChT-alone group, the ICI + ChT group demonstrated significantly improved PFS (8.07 vs. 6.87 months; p < 0.001) and OS (19.83 vs. 13.80 months; p = 0.001). The addition of ICIs to the ChT regimen did not significantly delay the onset of BMs compared to that with ChT alone (16.93 vs. 12.67 months; p = 0.379). Notably, the addition of TRT to the αPD-L1 + ChT regimen significantly prolonged BMFS compared to that without TRT (20.27 vs. 8.80 months; p = 0.045). In patients with ES-SCLC without baseline BMs, first-line chemoimmunotherapy significantly improves PFS and OS. However, it does not delay intracranial metastasis. The addition of TRT to αPD-L1 + ChT therapy significant delays the development of BMs. Not applicable.

Huang B ，Liu S ，Wang K ，Zhao J ，Li M ，Wang X ，Wang W ，Wang X ，Yu J ，Meng X ，Cai G ... -  《RESPIRATORY RESEARCH》

Efficacy and Safety of Anlotinib and PD-1/L1 Inhibitors as Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer Patients who Have Achieved Stable-Disease After First-Line Treatment with Chemotherapy and Immunotherapy: A Retrospective Study.

Peng Y ，Wu D ，Tang J ，Li X ... -  《-》

Immune checkpoint inhibitors plus platinum-based chemotherapy compared to platinum-based chemotherapy with or without bevacizumab for first-line treatment of older people with advanced non-small cell lung cancer.

Lung cancer is a cancer of the elderly, with a median age at diagnosis of 71. More than one-third of people diagnosed with lung cancer are over 75 years old. Immune checkpoint inhibitors (ICIs) are special antibodies that target a pathway in the immune system called the programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway. These antibodies help the immune system fight cancer cells by blocking signals that cancer cells use to avoid being attacked by the immune system. ICIs have changed the treatment of people with lung cancer. In particular, for people with previously-untreated advanced non-small cell lung cancer (NSCLC), current first-line treatment now comprises ICIs plus platinum-based chemotherapy, rather than platinum-based chemotherapy alone, regardless of their PD-L1 expression status. However, as people age, their immune system changes, becoming less effective in its T cell responses. This raises questions about how well ICIs work in older adults. To assess the effects of immune checkpoint inhibitors (ICIs) in combination with platinum-based chemotherapy compared to platinum-based chemotherapy (with or without bevacizumab) in treatment-naïve adults aged 65 years and older with advanced NSCLC. We searched the Cochrane Lung Cancer Group Trial Register, CENTRAL, MEDLINE, Embase, two other trial registers, and the websites of drug regulators. The latest search date was 23 August 2023. We also checked references and searched abstracts from the meetings of seven cancer organisations from 2019 to August 2023. We included randomised controlled trials (RCTs) that reported on the efficacy and safety of adding ICIs to platinum-based chemotherapy compared to platinum-based chemotherapy alone for people 65 years and older who had not previously been treated. All data emanated from international multicentre studies involving adults with histologically-confirmed advanced NSCLC who had not received any previous systemic anticancer therapy for their advanced disease. We used standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival and treatment-related adverse events (grade 3 or higher). Our secondary outcomes were progression-free survival, objective response rate, time to response, duration of response, and health-related quality of life (HRQoL). We included 17 primary studies, with a total of 4276 participants, in the review synthesis. We identified nine ongoing studies, and listed one study as 'awaiting classification'. Twelve of the 17 studies included people older than 75 years, accounting for 9% to 13% of their participants. We rated some studies as having 'some concerns' for risk of bias arising from the randomisation process, deviations from the intended interventions, or measurement of the outcome. The overall GRADE rating for the certainty of the evidence ranged from moderate to low because of the risk of bias, imprecision, or inconsistency. People aged 65 years and older The addition of ICIs to platinum-based chemotherapy probably increased overall survival compared to platinum-based chemotherapy alone (hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.70 to 0.88; 8 studies, 2093 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events may not differ between the two treatment groups (risk ratio (RR) 1.09, 95% CI 0.89 to 1.32; 1 study, 127 participants; low-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improves progression-free survival (HR 0.61, 95% CI 0.54 to 0.68; 7 studies, 1885 participants; moderate-certainty evidence). People aged 65 to 75 years, inclusive The addition of ICIs to platinum-based chemotherapy probably improved overall survival compared to platinum-based chemotherapy alone (HR 0.75, 95% CI 0.65 to 0.87; 6 studies, 1406 participants; moderate-certainty evidence). Only one study reported data for treatment-related adverse events (grade 3 or higher). The frequency of treatment-related adverse events probably increased in people treated with ICIs plus platinum-based chemotherapy compared to those treated with platinum-based chemotherapy alone (RR 1.47, 95% CI 1.02 to 2.13; 1 study, 97 participants; moderate-certainty evidence). The addition of ICIs to platinum-based chemotherapy probably improved progression-free survival (HR 0.64, 95% CI 0.57 to 0.73; 8 studies, 1466 participants; moderate-certainty evidence). People aged 75 years and older There may be no difference in overall survival in people treated with ICIs combined with platinum-based chemotherapy compared to platinum-based chemotherapy alone (HR 0.90, 95% CI 0.70 to 1.16; 4 studies, 297 participants; low-certainty evidence). No data on treatment-related adverse events were available in this age group. The effect of combination ICI and platinum-based chemotherapy on progression-free survival is uncertain (HR 0.83, 95% CI 0.51 to 1.36; 3 studies, 226 participants; very low-certainty evidence). Only three studies assessed the objective response rate. For time to response, duration of response, and health-related quality of life, we do not have any evidence yet. Compared to platinum-based chemotherapy alone, adding ICIs to platinum-based chemotherapy probably leads to higher overall survival and progression-free survival, without an increase in treatment-related adverse events (grade 3 or higher), in people 65 years and older with advanced NSCLC. These data are based on results from studies dominated by participants between 65 and 75 years old. However, the analysis also suggests that the improvements reported in overall survival and progression-free survival may not be seen in people older than 75 years.

Orillard E ，Adhikari A ，Malouf RS ，Calais F ，Marchal C ，Westeel V ... -  《Cochrane Database of Systematic Reviews》

Continuing immune checkpoint inhibitors after progression: Real-world patterns of care and outcomes in second-line treatment for extensive-stage small-cell lung cancer.

Small cell lung cancer (SCLC) is a highly malignant tumor with an extremely poor prognosis. In the currentera of immunotherapy, the role of immune checkpoint inhibitors (ICIs) in the second-line treatment of patients with extensive-stage SCLC (ES-SCLC) who have progressed to initial chemoimmunotherapy remains unclear. A multicenter retrospective study were conducted, involving patients with ES-SCLC who received second-line (2L) therapy after progression to first-line chemoimmunotherapy. Patients were divided into 2L-ICIs group and 2L-non-ICIs group according to whether ICIs were added to the 2L treatment. The efficacy and adverse events of the two groups were analyzed and compared. A total of 103 patients were included in this study, with 53 in the 2L-ICIs group and 50 in the 2L-non-ICIs group. The 2L-ICIs group demonstrated a longer median progression-free survival (PFS) compared to the 2L-non-ICIs group (4.4 months vs 3.9 months, HR = 0.45, p = 0.001). Similarly, median overall survival was also prolonged in the 2L-ICIs group (10.0 months vs 6.9 months, HR = 0.56, p = 0.015). Cox regression analysis revealed that the addition of ICIs to 2L treatment was an independent prognostic factor for both PFS and OS in ES-SCLC patients. Subgroup analysis indicated that patients with a first-line PFS of ≥6 months could potentially benefit more from 2L ICIs. Furthermore, the occurrence of adverse events in the two groups exhibited a similar pattern. For ES-SCLC patients who have progressed to first-line chemoimmunotherapy, adding ICIs to second-line treatment may be considered as an option with limited benefit but manageable adverse effects.

Zhang B ，Bao H ，Li Z ，Chen J ，Yu H ，Li M ，Cai M ，Chen L ... -  《-》

The Efficacy and Safety of Albumin-Bound Paclitaxel Combined With Anlotinib and PD-1/L1 Inhibitors For Treating Patients With Extensive-Stage Small Cell Lung Cancer and Brain Metastasis: A Retrospective Cohort Study.

Li X ，Wu D ，Peng Y ，Tang J ，Wu Y ... -  《Cancer Medicine》