Anlotinib combined with EP regimen as first-line treatment for extensive-stage small cell lung cancer: A retrospective study

e20136 Background: In recent years, the combination of immunotherapy and chemotherapy has emerged as a standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, these regimens generally offer a median progression-free survival (mPFS) of around 6 months and a median overall survival (mOS) of approximately 15 months, which does not provide a significant advantage over chemotherapy alone. Our previous study on the first-line treatment of ES-SCLC using anlotinib plus EP/EC regimen demonstrated a 9-months PFS and a 19-months OS. Unlike other PD-1 monoclonal antibodies based on the IgG4 subtype, Penpulimab is a novel PD-1 monoclonal antibody based on the IgG1 subtype, which prevents aggregation and avoids immune escape associated with IgG4 monoclonal antibodies. Therefore, we conducted a single-center study evaluating anlotinib combined with Penpulimab and the EP/EC regimen as a first-line treatment for ES-SCLC. Methods: ES - SCLC patients aged 18 to 80 years, not received any treatment, no significant cardiac, hepatic, or renal dysfunction. This regimen comprised Anlotinib Hydrochloride (10mg,QD, from day 1 to 14 of each 21-day cycle), Penpulimab (200md, on day 1 of each 21-day cycle), Etoposide (100 mg/m² on days 1-3 of each 21-day cycle), and either CBP (AUC=4-5 on day 1 every 3 weeks) or DDP (70-75 mg/m² on day 1 every 3 weeks). The combination therapy was administered for 4 to 6 cycles. Following this, maintenance therapy with Anlotinib Hydrochloride (10mg ,qd, from day 1 to 14 of each 21-day ) and Penpulimab (200 mg on day 1 of each 21-day) was continued until disease progression or the occurrence of an intolerable adverse reaction. If Anlotinib was not tolerated, its dose could be reduced to 8 mg. The primary endpoints of observation included objective response rate (ORR), PFS, OS, and adverse reactions (ADR). Results: Between March 6, 2021, and March 31, 2024, a total of 25 patients with ES-SCLC were enrolled in this study and completed the treatment regimen. The mean age of the patients was 65.0 ± 8.5 years (range: 45-80 years), with 18 males (72%) and 7 females (28%). The median PFS was 11.0 months (95% CI: 9.38-12.62), and the median OS was 23.0 months (95% CI: 15.66-30.34). The ORR was 90%, and the DCR was 100%. Grade 3 or higher adverse reactions included neutropenia in 15 patients (60%), thrombocytopenia in 10 patients (40%), nausea and vomiting in 7 patients (28%), anemia in 3 patients (12%), fatigue in 8 patients (32%), hypertension and elevated transaminase levels in 5 patients each (20%), and hoarseness in 1 patients (4%). Conclusions: The combination of Anlotinib with Penpulimab and EP/EC regimens, has demonstrated superior PFS, OS, ORR, and DCR in initial ES-SCLC treatments, with manageable adverse events. A randomized, controlled phase III clinical study will be conducted to further validate these promising results. Clinical trial information: ChiCTR2200065238 .

BackgroundImmunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC.MethodsWe conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1).ResultsBetween January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3–8.1) was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5–7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83–1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62–1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group.ConclusionsOur research revealed that there were no significant differences in efficacy or prognosis between PD-1 inhibitor + EP chemotherapy and PD-L1 inhibitor + EP chemotherapy. The two groups seemed to have comparable safety profiles, but the number of discontinuation or death events was too small to draw a firm conclusion.

BackgroundImmunotherapy targeting PD-1/PD-L1 has revolutionized the treatment of extensive-stage small cell lung cancer (ES-SCLC). However, clinical trials suggest differential efficacy of anti-PD-1 agents and anti-PD-L1 agents in first-line treatment of ES-SCLC. This retrospective multicenter study aimed to compare the efficacy and safety of anti-PD-1 agents versus anti-PD-L1 agents in first-line treatment of ES-SCLC in real-world practice.MethodsPatients with pathologically or cytologically confirmed ES-SCLC treated with platinum plus etoposide combined with anti-PD-1 or PD-L1 agents as first-line treatment in different centers of PLA General Hospital between January 2017 and October 2021 were included for this study. Survival outcomes and safety were compared between patients receiving anti-PD-1 and PD-L1 agents.ResultsOf the total 154 included patients, 68 received anti-PD-1 agents plus chemotherapy (PD-1 group), and 86 received anti-PD-L1 agents plus chemotherapy (PD-L1 group). Progression-free survival (PFS) and overall survival (OS) in the entire cohort were 7.6 months (95% confidence interval [CI]: 6.5–8.2 months) and 17.4 months (95% CI: 15.3–19.3 months), respectively. Median PFS and OS were comparable between the PD-1 group and PD-L1 group (PFS: 7.6 months vs. 8.3 months, HR = 1.13, 95% CI: 0.79–1.62, p = 0.415; OS: 26.9 months vs. 25.6 months, HR = 0.96, 95% CI: 0.63–1.47, p = 0.859. The objective response rate and disease control rate were comparable between the two groups: 79.4% vs. 79.1% and 92.6% vs. 94.2%, respectively. The 6-month, 12-month, and 18-month PFS and OS rates were slightly higher in the PD-L1 group than in the PD-1 group, while the 24-month PFS rate was slightly higher in the PD-1 group than in the PD-L1 group. Stratified analysis showed that locoregional thoracic radiotherapy and normal lactate dehydrogenase level were independent predictors of better OS in ES-SCLC patients treated with first-line chemotherapy plus ICI. Adverse events were not significantly different between the two groups.ConclusionsAnti-PD-1 agents and anti-PD-L1 agents combined with chemotherapy as first-line treatment for ES-SCLC are comparably effective and well tolerated.

The integration of chemotherapy and immunotherapy as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) has been adopted in clinical practice, yet the response to immune checkpoint inhibitors (ICIs) is variable, benefiting only a fraction of patients. The current absence of reliable biomarkers for predicting treatment response and prognosis represents a significant gap in knowledge, hindering the optimization of patient stratification and treatment planning. This retrospective cohort study aims to assess the potential predictive and prognostic significance of clinicopathological baseline features in ES-SCLC patients. Our study retrospectively analyzed the data of consecutive patients with ES-SCLC treated with first-line etoposide plus platinum chemotherapy ± immunotherapy at The Affiliated Lihuili Hospital of Ningbo University from April 2017 to April 2023. Data on clinical information, serum laboratory indicators, pathological immunohistochemical markers, and progression-free survival (PFS) times were collected. Univariate and multivariate Cox regression analyses were employed to determine whether these indicators could serve as independent prognostic factors for PFS. Further, potential predictive markers for treatment efficacy were identified using a Cox regression model that incorporated an interaction term between treatment modality and the indicator. A total of 121 patients with ES-SCLC were enrolled in the study, of whom 62 received chemotherapy alone, and 59 received chemotherapy in combination with immunotherapy. Compared to chemotherapy alone, the addition of immunotherapy to first-line chemotherapy significantly extended the PFS time [P<0.001; hazard ratio (HR) =0.42; 95% confidence interval (CI): 0.28, 0.64] of the ES-SCLC patients. The multivariate analysis revealed that an immunochemotherapy regimen (P<0.001, HR =0.40; 95% CI: 0.24, 0.68), a low-density lipoprotein (LDL) level of >1.8 mmol/L (P=0.02; HR =0.41; 95% CI: 0.20, 0.85) were independent prognostic factors of favorable PFS in the first-line treatment of all ES-SCLC, while a lactate dehydrogenase (LDH) level of >273 U/L (P=0.04; HR =1.78; 95% CI: 1.03, 3.07), a neuron-specific enolase (NSE) concentration of >102.6 ng/mL (P=0.009; HR =6.49; 95% CI: 1.60, 26.32), an apolipoprotein A1 (ApoA1) concentration of >0.9 g/L (P<0.001; HR =4.15; 95% CI: 1.98, 8.71), and an apolipoprotein B (ApoB) concentration of >0.8 g/L (P=0.002; HR =2.24; 95% CI: 1.34, 3.75) were independent prognostic factors of poorer PFS. Further, the interaction effect analysis demonstrated that an LDL level of >1.8 mmol/L and the absence of bone metastasis were potential predictors of an improved response to ICI therapy compared to chemotherapy alone. This study showed the survival benefit of receiving a chemoimmunotherapy regimen as the first-line treatment in a real-world scenario. It also suggests the prognostic significance of pre-treatment LDL, LDH, NSE, ApoA1, and ApoB with optimal cut-off values in the first-line treatment of all ES-SCLC, and the potential utility of baseline LDL level or the presence of bone metastasis in guiding first-line treatment strategies.

Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC. This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis. A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9months of follow-up, median PFS and OS was 6.8months (95%CI 5.7-7.8), and 11.9months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable. This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC.

Topotecan and Paclitaxel in Previously Treated Patients with Relapsed Small Cell Lung Cancer: Phase II Trial of the North Central Cancer Treatment Group

Immune checkpoint inhibitors have recently become the standard of care in the first-line treatment of extensive-stage small cell lung cancer. Although immune-related adverse events have been reported to influence prognosis in non-small cell lung cancer patients, few studies have investigated the prognostic value of immune-related adverse events in small cell lung cancer patients. In this study, we evaluated the prognosis of patients who developed immune-related adverse events after first-line treatment with immune checkpoint inhibitor-based chemotherapy for extensive-stage small cell lung cancer. We enrolled 90 patients with extensive-stage small cell lung cancer who received immune checkpoint inhibitor-based chemotherapy as first-line treatment from September 2019 to December 2022 in six hospitals in Japan. The patients were categorized into groups with and without immune-related adverse events. There were 23 patients with and 67 without immune-related adverse events. Seventeen patients had grade 1-2 immune-related adverse events, and nine (including overlapping cases) had grade ≥3. The most frequent immune-related adverse event was a skin rash. The median survival time was 22 months in patients with immune-related adverse events and 9.3 months in patients without immune-related adverse events. The hazard ratio was 0.40 (95% confidence interval: 0.19-0.83, p = 0.013). The results of this study show that immune-related adverse events are associated with improved survival outcomes in patients with extensive-stage small cell lung cancer.

Survival outcomes with carboplatin versus cisplatin and the impact of COVID-19 on platinum choice: A nationwide Netherlands registry study in small cell lung cancer patients (CACIS).

Background Immunochemotherapy has been approved as first-line treatment for extensive-stage small cell lung cancer. However, second-line treatment options and whether continuous immunotherapy will improve clinical outcome are still controversial. This multi-center retrospective study aimed to investigate the efficacy of continuous immunotherapy for the patients who suffered progression from first-line immunochemotherapy. Methods We retrospectively reviewed the medical records of patients with extensive-stage small cell lung cancer treated with first-line immunochemotherapy in three major medical centers in Shandong Province. The patients enrolled achieved disease control during first-line immunochemotherapy but subsequently suffered disease progression. Results From January 2020 to December 2024, a total of 354 patients treated with first-line immunochemotherapy were enrolled. The first-line progression free survival was 6.60 (95%CI: 6.28-6.92) months. A total of 206 patients were enrolled to compare the efficacy of second-line therapies, including chemotherapy alone (C, 40 cases), chemotherapy + anti-angiogenic therapy (C+A, 17 cases), immunochemotherapy (I+C, 122 cases), immunotherapy + anti-angiogenic therapy (I+A, 11 cases) and immunochemotherapy + anti-angiogenic therapy (I+C+A, 16 cases). Therein, I+C+A group obtained the longest second-line progression free survival of 4.60 (95%CI: 2.71-6.50) months. The second-line progression free survival of I+C group was also longer than that of the C group (3.50, 95%CI: 3.07-3.93 vs 2.33, 95%CI: 1.66-3.01). Regarding overall survival, I+A group achieved the longest overall survival of 22.00 (95%CI: 11.39-32.61) months compared with 19.53 (95%CI: 16.81-22.26) months for I+C group. However, there were no statistical differences in second-line progression free survival and overall survival among the groups. In terms of safety, the rates of adverse events in the I+C and C groups were not statistically significant. Conclusions Continuous immunotherapy beyond progression in extensive-stage small cell lung cancer shows the trend of prolonging second-line progression free survival, but does not improve the overall survival. Additionally, in the second-line treatment, chemotherapy remains an important cornerstone therapy and anti-angiogenic agent containing strategy may potentially improve survival.

Immunotherapy combined with chemotherapy is the first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, the effect of delayed initiation of immunotherapy on its efficacy remains unclear. This study aimed to investigate the impact of the delayed addition of programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) inhibitors on treatment outcomes in patients with ES-SCLC. This retrospective cohort study used propensity score matching (PSM) to balance baseline characteristics. This study included 416 patients with ES-SCLC who received first-line immunotherapy between January 2020 and December 2022. Patients were categorized into two groups: delayed-immunotherapy (IO) (PD-1/PD-L1 inhibitors initiated during the 2nd or 3rd chemotherapy cycle) and early-IO (immunotherapy initiated during the first cycle). A 1:1 PSM was performed to balance baseline characteristics. The primary endpoints were overall survival (OS) and progression-free survival (PFS), which were analyzed using the Kaplan-Meier method and compared using log-rank tests. Owing to the exclusion of PD-L1/PD-1 inhibitors from medical insurance, financial constraints, and poor physical condition of some patients, 72 patients were included in the delayed-IO group (second cycle: 41; third cycle: 31), while 344 were in the early-IO group. Before PSM, median OS and PFS in the delayed-IO group were 24.00 and 8.75 months, compared to 18.59 and 7.57 months in the early-IO group, with no significant differences (OS: HR 0.72, p = 0.054; PFS: HR 0.86, p = 0.281). After PSM (72 patients per group), the delayed-IO group showed significantly longer median OS (24.00 vs 18.79 months, HR 0.60, 95% CI 0.38-0.97, p = 0.037) and PFS (8.75 vs 6.49 months, HR 0.69, 95% CI 0.48-0.99, p = 0.044) compared to the early-IO group. These results suggest that, in specific patient populations, delayed immunotherapy may improve survival outcomes by optimizing patient condition or treatment response. In patients with ES-SCLC, delayed administration of PD-1/PD-L1 inhibitors during the second to fourth chemotherapy cycles improves survival outcomes compared to concurrent administration during the first cycle, with a similar safety profile. These results suggest that, in specific patient populations, delayed immunotherapy may improve survival outcomes by optimizing patient condition or treatment response.

Deep analysis of the trials and major challenges in the first-line treatment for patients with extensive-stage small cell lung cancer.

Background: Immunotherapy in combination with platinum-etoposide (EP) chemotherapy has been approved as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). However, real-world (RW) data regarding the use of immune checkpoint inhibitors (ICIs) in ES-SCLC are lacking. We aimed to assess the differences between programmed death protein 1 (PD-1) inhibitors and programmed death ligand 1 (PD-L1) inhibitors, both in conjunction with EP chemotherapy, as first-line treatment for ES SCLC. Methods: We conducted a real-world, multicenter, retrospective cohort, controlled study to compare the prognosis, efficacy, and safety of PD-1 and PD-L1 inhibitors in ES-SCLC patients when used along with chemotherapy. Each patient received up to six cycles of etoposide, carboplatin, or cisplatin combined with ICI drugs, including PD-1 and PD-L1 inhibitors. The primary endpoints were investigator-assessed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the investigator-assessed objective response rate (ORR) and disease control rate (DCR) according to the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results: Between January 2017 and December 2021, 194 patients with ES-SCLC from three clinical centers in a PLA general hospital were included in our study, including 93 patients in the PD-1 group and 101 patients in the PD-L1 group. At the time of data cutoff, progression-free survival in the PD-1 group (median PFS, 6.8 months; 95% CI, 5.3–8.1 was similar to that in the PD-L1 group (median PFS, 6.4 months; 95% CI, 5.5–7.5); the stratified hazard ratio for PFS was 1.12 (95% CI, 0.83–1.53; P = 0.452). The median OS was similar in the PD-1 and PD-L1 groups (15.8 m vs. 17.7 m, P = 0.566); the hazard ratio was 0.90 (95% CI, 0.62–1.30, P = 0.566). The two groups had comparable investigator-assessed confirmed objective response rates (ORR) (76.3% vs. 76.2%). Adverse effect (AE)-related discontinuation occurred in 4 (4.3%) patients in the PD-1 group and 2 (2.0%) patients in the PD-L1 group. Deaths due to AEs of any cause occurred in 2 (2.2%) patients in the PD-1 inhibitor group and 1 (1.0%) patient in the PD-L1 inhibitor group.

e20110 Background: This study aims to evaluate whether the combination of chemotherapy and immunotherapy offers superior efficacy and prognosis compared to chemotherapy alone in the real-world first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). The ultimate goal is to provide evidence that can guide clinical practice more effectively. Methods: This study is a single-center retrospective analysis of data collected from 574 patients with ES-SCLC treated at the Fourth Hospital of Hebei Medical University. The data included clinicopathological characteristics, baseline peripheral blood biomarkers, treatment modalities, prognostic outcomes, and efficacy indicators. Propensity score matching was conducted between the chemotherapy group and the chemotherapy combined with immunotherapy group to ensure comparable baseline clinicopathological characteristics.Kaplan-Meier analysis was employed to estimate progression-free survival (PFS) and overall survival (OS) in patients with ES-SCLC. Univariate Cox regression analysis was conducted to evaluate the hazard ratios associated with different baseline characteristics across the two treatment regimens.The results further confirmed that the chemotherapy combined with immunotherapy group demonstrated superior efficacy and prognosis compared to the chemotherapy group.Differences were considered statistically significant at P &lt; 0.05. Results: By the last follow-up on October 15, 2024, the median follow-up duration was 12 months, with a total of 434 deaths (75.6%) recorded. The objective response rates (ORR) were 75.6% for the first-line chemotherapy plus immunotherapy group and 60.4% for the chemotherapy-only group. The 1-year, 2-year, and 3-year overall survival (OS) rates were 35%, 23%, and 23%, respectively, in the combined therapy group, compared to 23%, 14%, and 12% in the chemotherapy-only group. The median progression-free survival (mPFS) was 8 months (95% CI: 7.0–8.9) in the combined therapy group, compared to 6 months (95% CI: 5.5–6.4) in the chemotherapy-only group. The median overall survival (mOS) was 15 months (95% CI: 12.2–17.7) in the combined therapy group and 13 months (95% CI: 11.6–14.3) in the chemotherapy-only group. Univariate analysis revealed that, in the overall population and across baseline characteristics—including gender, age, smoking status, ECOG performance status, and the presence of brain, bone, or liver metastases—the first-line chemotherapy plus immunotherapy group had reduced risks of progression and mortality compared to the chemotherapy-only group. Conclusions: This retrospective study further confirmed that in real-world first-line treatment of ES-SCLC, chemotherapy combined with immunotherapy provides superior efficacy and prognosis compared to chemotherapy alone.

P2.04-86 Efficacy of Ipilimumab in Combination with Chemotherapy for First-Line Treatment of Advanced Lung Cancer

The landmarks of Thoracic Oncology in the last two decades have been accompanied by exponential growth in costs, making it imperative to assess the real benefit of incorporating new technologies. Combining immunotherapy (IO) with platinum-etoposide chemotherapy has become the standard of care in first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). However, the absolute difference in overall survival (OS) has reached three months. This study aimed to investigate the impact of this intervention in a real-world cohort. We retrospectively analyzed data from ES-SCLC patients (pts) from a Brazilian Oncology Group, diagnosed and treated between January 2018 and June 2022. The primary objectives were median OS (mOS) and median time to subsequent treatment (mTST) according to IO exposure in the first-line setting. Secondarily, we intend to compare these results with the literature data and with an internal and contemporary cohort of patients treated with chemotherapy alone. In total, 85 SCLC patients were included in this analysis. The median follow-up was nine months. First line regimens were atezolizumab + platinum-etoposide in 53%, platinum-etoposide in 36% and platinum-irinotecan in 11%. Among ES-SCLC pts who received IO in their first-line treatment, the mOS was 15.0 months (95% CI: 11.20; 18.80) and the mTST was 8.0 months (95% CI: 6.25; 9.75). As a reference, our internal and contemporary control presented numerically lower mOS and mTST: 9.0 months (95% CI: 2.08; 19.92) and 7.0 months (95% CI: 5.88; 8.12), respectively. Few real-world cohorts are evaluating the impact of IO in ES-SCLC, limited to high-income countries. Our data suggest that IO has a meaningful impact on the outcome of ES-SCLC in daily clinical practice, confirming previous trial results.