Recent treatment patterns and real-world survival following first-line anti-PD-L1 treatment for extensive-stage small cell lung cancer.

The landscape of small cell lung cancer (SCLC) has changed since the 2019 and 2020 approvals of anti-PD-L1 atezolizumab and durvalumab for first-line (1L) treatment in combination with chemotherapy. We studied treatment patterns and real-world overall survival (rwOS) following 1L-3L therapy. A nationwide electronic health record (EHR)-derived de-identified database was used to describe treatment patterns, characteristics, and survival of patients with extensive-stage (ES)-SCLC by 1L anti-PD-L1 treatment. Patients with ES-SCLC who initiated ≥1 line of systemic therapy from 2013 to 2021, with potential follow-up through 2022, were included. Among 9952 patients with SCLC, there were 4308 patients with ES-SCLC treated during the study period who met eligibility criteria. Etoposide + platinum (EP) chemotherapy was most common in the 1L, with addition of anti-PD-L1 therapy to most regimens by 2019. Second-line regimens varied by platinum sensitivity status and shifted from topotecan to lurbinectedin over time. Median rwOS following 1L therapy was 8.3 months (95% CI, 7.9-8.8) in those treated with 1L anti-PD-L1 and 8.0 months (95% CI, 7.8-8.2) in those who were not. Following 2L and 3L, median rwOS was 5.6 (95% CI, 4.9-6.3) and 4.9 months (95% CI, 3.4-6.0), respectively, among 1L anti-PD-L1-treated, and 4.5 (95% CI, 4.2-4.9) and 4.0 months (95% CI, 3.7-4.5), respectively, among those who were not. Despite the introduction of frontline anti-PD-L1 therapy, survival remains dismal among patients with ES-SCLC treated in the real-world setting.

Shaw J ，Pundole X ，Balasubramanian A ，Anderson ES ，Pastel M ，Bebb DG ，Jiang T ，Martinez P ，Ramalingam SS ，Borghaei H ... -  《-》

Real-world comparison of the efficacy and safety of atezolizumab versus durvalumab in extensive-stage small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive disease associated with high relapse rates and limited treatment options. Current standard of care treatment for extensive-stage disease includes combination chemotherapy plus immunotherapy. Programmed death ligand-1 (PD-L1) immune checkpoint inhibitors (ICIs) are preferred first-line treatments in combination with chemotherapy with both atezolizumab and durvalumab being equivalent options. Although both ICIs are listed as front-line options in clinical guidelines, there have been no head-to-head trials comparing durvalumab to atezolizumab. Therefore, it is unknown if either agent is superior with regards to efficacy or safety. This retrospective, single-institution study examined patients with extensive-stage small cell lung cancer presenting to Moffitt Cancer Center between October 1st, 2018 to May 31st, 2023 who received either atezolizumab or durvalumab in combination with a platinum-doublet in the first-line setting. To be included in this analysis patients must have received at least two cycles of induction chemotherapy and ICI and one cycle of maintenance ICI. The primary outcome of this study was overall survival. The secondary outcomes include progression-free survival, immune-related adverse events, hospitalizations due to ICIs, and progression-free survival on second-line therapy (PFS2). Of the 101 patients included, 55 received durvalumab (54.5 %) and 46 received atezolizumab (45.5 %). The median overall survival in the durvalumab and atezolizumab arms were 14.7 versus 11.6 months, respectively (HR 0.59; 95 % CI, 0.38-0.92; P = 0.020). There was not a statistically significant difference in median progression-free survival between the two arms (6.3 versus 5.9 months, P = 0.344). Atezolizumab was associated with a numerically higher incidence of immune-related adverse events (47.8 % versus 32.7 %, P = 0.157) and hospitalization rates for those with an immune-related adverse event (36.4 % versus 16.7 %, P = 0.204). PFS2 was 2.3 months in the atezolizumab arm and 3.4 months in the durvalumab arm (HR 1.24; 95 % CI, 0.69-2.23; P = 0.466). In this real-world retrospective study, durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer consistent with previous findings from a similar study in a Chinese patient population. Although not statistically significant, there was a lower incidence of immune-related adverse events in the durvalumab arm as well as ICI-related hospitalizations. PFS2 was not statistically significant different between arms.

Vince M ，Naqvi SMH ，Pellini B ，Verbosky M ，Melzer D ... -  《-》

Comparison of efficacy and safety of PD-1/PD-L1 combination therapy in first-line treatment of advanced NSCLC: an updated systematic review and network meta-analysis.

The use of immune checkpoint inhibitors has led to an increase in randomized controlled trials exploring various first-line combination treatment regimens. With the introduction of new PD-1/PD-L1 inhibitors, there are now more clinical options available. For the first time, the AK105 monoclonal antibody Penpulimab, developed in China, was included. The AK105-302 Phase III trial studied the efficacy and safety of Penpulimab combined with chemotherapy in patients with advanced or metastatic squamous NSCLC. To determine the optimal treatment options, we conducted an updated network meta-analysis to compare the effectiveness and safety of these regimens. The system retrieves data from Chinese and English electronic databases, Clinical Trials, and the gov Clinical Trial Registration website up to September 6, 2023. The study indirectly compared the efficacy and safety of PD-1/PD-L1 combination regimens, including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), all-grade adverse events, and above-grade III adverse events. Subgroup analyses were conducted based on programmed death ligand 1 (PD-L1) level, histological type, ECOG score, sex, and smoking history. Nineteen RCTS were included, with a total of ten thousand eight hundred patients. Penpulimab plus chemotherapy (Pen + CT) provided the best OS (HR = 0.55, 95% CI 0.38-0.81) for PD-L1 patients with non-selective advanced NSCLC. Except Nivolumab plus Ipilimumab (Niv + Ipi), other PD-1/PD-L1 combination therapies significantly extended PFS compared with CT, and Nivolumab plus Bevacizumab combined with chemotherapy (Niv + Bev + CT) (HR = 0.43, 95% CI 0.26-0.74) provided the best PFS benefit and was comparable to Pen + CT (HR = 1.0) for PFS prolongation. For ORR, except Niv + Ipi, all the other regimens significantly improved ORR compared with CT. In terms of safety, except Tor + CT, the incidence of any-grade AEs or grade ≥ 3 adverse events may be higher than those of chemotherapy. The subgroup analysis revealed that for patients with PD-L1 levels below 1%, treatment with Tor + CT resulted in the best progression-free survival (HR = 0.47, 95% CI 0.25-0.86). For patients with PD-L1 levels of 1% or higher, Sintilimab plus chemotherapy (Sin + CT) (HR = 0.56, 95% CI 0.31-0.99) and Camrelizumab plus chemotherapy (Cam + CT) (HR = 0.43, 95% CI 0.28-0.64) were associated with the best overall survival and progression-free survival, respectively. For patients with SqNSCLC, combined immunotherapy may provide greater survival benefits. For patients with Non-sqNSCLC, Niv + Bev + CT and Tor + CT were associated with optimal PFS and OS, respectively. Cam + CT provided the best PFS in male patients with a history of smoking and an ECOG score of 0. In both female and non-smoking patient subgroups, Pem + CT was associated with the best PFS and OS benefits. For patients with advanced non-selective PD-L1 NSCLC, two effective regimens are Pen + CT and Niv + Bev + CT, which rank first in OS and PFS among all patients. Cam + CT and Tor + CT have advantages for OS in patients with SqNSCLC and Non-sqNSCLC, respectively. Niv + Ipi + CT provided the best OS benefit for patients with an ECOG score of 0, while Pem + CT may be the most effective treatment for patients with an ECOG score of 1. Pem + CT has a better effect on female patients and non-smokers. Sin + CT was found to be the most effective treatment for male patients and the smoking subgroup, while Cam + CT was found to be the most effective for PFS. In addition, Tor + CT was associated with the best PFS for patients with negative PD-L1 expression. Pem + CT was found to significantly improve both PFS and OS compared to CT alone. For patients with positive PD-L1 expression, Sin + CT and Cam + CT were found to be optimal for OS and PFS, respectively. It is important to note that, with the exception of Tor + CT, the toxicity of the other combinations was higher than that of CT alone.

Yang Y ，Chen W ，Dong L ，Duan L ，Gao P ... -  《-》

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》

Efficacy and safety of immunotherapy combined with chemotherapy in patients with ES-SCLC: A systematic review and network meta-analysis of RCTs and RWSs.

To 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). By 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). Compared 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. In 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.

Kang R ，Ma J ，Ai B ，Liu J ，Zheng Z ，Yu J ... -  《-》