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).

P50.10 Intravenous (IV) versus IV/oral route of etoposide administration: impact on real-world SCLC survival outcomes

The prognostic factors for the survival of small cell lung cancer (SCLC) patients are still widely debated. The aim of this study was to identify the clinical features and prognostic factors in SCLC patients. A retrospective study was conducted on SCLC patients who were treated in our hospital between July 2010 and July 2015. Comparison of overall survival (OS) was performed using the Kaplan-Meier method. Prognostic factors for OS were identified by multivariate Cox regression models. A total of 523 patients with complete data and ECOG 0-2 were enrolled in our study. A total of 383 patients (73.2%) were diagnosed with ES-SCLC (extensive-stage SCLC) and 140 patients (26.8%) were diagnosed with LS-SCLC (limited-stage SCLC). In all patients, early disease stage, good ECOG, normal neuron-specific enolase (NSE), thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation, good response to initial therapy were independent favorable prognostic factors for OS, along with gender, age, CEA and CA125. In LS-SCLC patients, normal NSE, normal CEA, good response to initial therapy and surgery were independent favorable prognostic factors for OS. In ES-SCLC patients, good ECOG, normal NSE, thoracic radiotherapy, ≥4 cycles of chemotherapy, prophylactic cranial irradiation and good response to initial therapy were independent favorable prognostic factors for OS. Remarkably, NSE and response to initial therapy were independent prognostic factors for OS in all SCLC patients, LS-SCLC patients and ES-SCLC patients. The normal NSE and good response to initial therapy predicted a better survival for SCLC patients, regardless of disease stage.

Small cell lung cancer (SCLC) is characterized by an exceedingly low mutation rate in oncogenic driver alterations, and there are currently no articles or case reports documenting SCLC patients carrying ROS1 fusions. Tyrosine kinase inhibitors (TKIs) have demonstrated significant efficacy and safety in patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC). However, effective treatment modalities for ROS1 fusion-positive SCLC patients remain poorly defined. We report the first case of an extensive-stage SCLC (ES-SCLC) patient harboring ROS1 fusion, along with TP53, RB1, PTEN, and TERT mutations. The patient exhibited primary resistance to a 3-week course of crizotinib as first-line treatment. Following this, the patient was administered second-line therapy, including chemotherapy coupled with immune checkpoint inhibitor (ICI) and ICI maintenance treatment, resulting in a partial response (PR). Notably, the clinical response to second-line therapy persisted for over 19 months, surpassing the previously reported efficacy of immuno-chemotherapy in ES-SCLC cases (5.7 months) while maintaining a satisfactory quality of life. We hypothesize that ROS1 fusion may not function as an oncogenic driver alteration in ES-SCLC. Immuno-chemotherapy, not ROS1-TKIs, might provide superior efficacy in ES-SCLC patients with ROS1 fusion.

BackgroundAnlotinib is a multi-targeted tyrosine kinase inhibitor that inhibits tumor angiogenesis which has shown activity in several malignancies and approved for the treatment of small cell lung cancer (SCLC) in China. However, there are no markers can predict the clinical outcomes of anlotinib. We aimed to evaluate the efficacy of anlotinib in extensive stage SCLC (ES-SCLC) patients who failed at least two regimens treatment and to explore potential factors related to its survival benefit.MethodsPatients with ES-SCLC treated with anlotinib monotherapy were screened between March 2017 and May 2019, prognostic nutritional index (PNI) before treatment were collected. Progression free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan–Meier method and the log-rank test. The prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression (PHR) analyses.ResultsA total of 41 patients with ES-SCLC were received anlotinib treatment, the median age was 57 (range, 33–76). Median OS was significantly longer in the PNI high arm compared with the low arm [8.4 months (95% CI, 5.1–9.6 months) vs. 4.7 months (95% CI, 2.1–6.3 months); hazard ratio (HR) 0.42 (95% CI, 0.21–0.85); P=0.01]. The median PFS of two arms were 4.1 months (95% CI, 2.1–8.2 months) and 2.6 months (95% CI, 0.7–3.9 months), respectively (HR =0.53, 95% CI, 0.27–1.02, P=0.05). Multivariate analysis confirmed that PNI (P<0.01) and LDH (P<0.01) were significant independent biomarkers for OS.ConclusionsThe present study demonstrated that pretreatment PNI can be used as a novel and convenient biomarker to predict the prognosis in ES-SCLC patients treated with anlotinib.

The current standard of care for the treatment of small cell lung cancer (SCLC) is concurrent chemoradiation for patients with limited-stage SCLC (LS-SCLC) and chemoimmunotherapy for extensive-stage SCLC (ES-SCLC). The backbone of chemotherapy regimens in both is a platinum-etoposide doublet: cisplatin is traditionally the preferred platinum agent in the curative intent setting, whereas carboplatin is preferred in ES-SCLC because of its favorable toxicity profile. To determine whether cisplatin is associated with better survival outcomes than carboplatin in treating LS-SCLC and ES-SCLC. In this cohort study, data were compiled from the National Veterans Affairs Central Cancer Registry for patients with SCLC who received platinum-based multiagent chemotherapy between 2000 and 2020 for ES-SCLC and 2000 and 2021 for LS-SCLC. Only patients with pathologically confirmed cases of LS-SCLC who received concurrent chemoradiation and ES-SCLC who received chemotherapy were included. The primary end point was overall survival (OS). The secondary end points included OS by Eastern Cooperative Oncology Group performance status, age, and laterality. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median OS and hazard ratios (HRs), respectively. Survival curves were compared by a Wald test. A total of 4408 SCLC cases were studied. Most patients were White (3589 patients [81.4%]), male (4252 [96.5%]), and non-Hispanic (4142 [94.0%]); 2262 patients (51.3%) were 60 to 69 years old, followed by 1476 patients (33.5%) aged 70 years or older, 631 patients (14.3%) aged 50 to 59 years, and 39 patients (0.9%) aged 30 to 49 years. Among 2652 patients with ES-SCLC, 2032 were treated with carboplatin-based therapy and 660 received cisplatin; the median OS was 8.45 months (95% CI, 7.75-9.20 months) for cisplatin and 8.51 months (95% CI, 8.07-8.97 months) for carboplatin (HR, 1.01; 95% CI, 0.91-1.12; P = .90). Subset analysis showed no survival difference between the 2 agents in different age or performance status groups except for patients aged 70 years and older, for whom the median OS was 6.36 months (95% CI, 5.31-7.56 months) for cisplatin and 8.47 months (95% CI, 7.79-9.19 months) for carboplatin (HR, 0.77; 95% CI, 0.61-0.96; P = .02). Multivariable analysis of performance status and age did not show a significant difference in survival between the 2 groups (HR, 0.96; 95% CI, 0.83-1.10; P = .54). Of 1756 patients with LS-SCLC, 801 received carboplatin, and 1018 received cisplatin. The median OS was 26.92 months (95% CI, 25.03-28.81 months) for cisplatin and 25.58 months (95% CI, 23.64-27.72 months) for carboplatin (HR, 1.04; 95% CI, 0.94-1.16; P = .46). The median OS was not significantly different between 2 agents according to cancer stage (I-III), performance status, and age groups. A multivariable analysis of factors associated with OS accounting for stage (I-III), performance status, and age did not demonstrate a significant difference in survival between carboplatin and cisplatin in patients with LS-SCLC (HR, 0.995; 95% CI, 0.86-1.15; P = .95). Cisplatin is not associated with a survival advantage over carboplatin among patients with either ES-SCLC or LS-SCLC, irrespective of performance status and age. The favorable toxicity profile of carboplatin and comparable OS support its use in both LS-SCLC and ES-SCLC in clinical practice and may allow more room for combination with novel treatment strategies in clinical trials.

To evaluate the effect of Chinese medicine (CM) treatment on survival time and quality of life (QOL) in patients with small cell lung cancer (SCLC). This was an exploratory and prospective clinical observation. Patients diagnosed with SCLC receiving CM treatment were included and followed up every 3 months. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and QOL. A total of 136 patients including 65 limited-stage SCLC (LS-SCLC) patients and 71 extensive-stage SCLC (ES-SCLC) patients were analyzed. The median OS of ES-SCLC patients was 17.27 months, and the median OS of LS-SCLC was 40.07 months. The survival time was 16.27 months for SCLC patients with brain metastasis, 9.83 months for liver metastasis, 13.43 months for bone metastasis, and 18.13 months for lung metastasis. Advanced age, pleural fluid, liver and brain metastasis were risk factors, while longer CM treatment duration was a protective factor. QOL assessment indicated that after 6 months of CM treatment, scores increased in function domains and decreased in symptom domains. CM treatment might help prolong OS of SCLC patients. Moreover, CM treatment brought the trend of symptom amelioration and QOL improvement. These results provide preliminary evidence for applying CM in SCLC multi-disciplinary treatment.

Real-world clinical experience of using anti-programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (SCLC) patients has rarely been reported. In this study, we aimed to perform a retrospective multicenter clinical analysis of extensive-stage SCLC patients receiving first-line therapy with anti-PD-L1 ICIs combined with chemotherapy. Between November 2018 and March 2022, 72 extensive-stage SCLC patients receiving first-line atezolizumab or durvalumab in combination with chemotherapy, according to the cancer center databases of Linkou, Chiayi, and Kaohsiung Chang Gung Memorial Hospitals, were retrospectively included in the analysis. Twenty-one patients (29.2%) received atezolizumab and fifty-one (70.8%) received durvalumab. Objective response (OR) and disease control (DC) rates of 59.7% and 73.6%, respectively, were observed with first-line ICI plus chemotherapy. The median progression-free survival (PFS) was 6.63 months (95% confidence interval (CI), 5.25–8.02), and the median overall survival (OS) was 16.07 months (95% CI, 15.12–17.0) in all study patients. A high neutrophil-to-lymphocyte ratio (NLR; >4) and a high serum lactate dehydrogenase (LDH) concentration (>260 UL) were identified as independent unfavorable factors associated with shorter OS in the multivariate analysis. Regarding safety, neutropenia was the most common grade 3 treatment-related adverse event (AE), but no treatment-related deaths occurred in the study patients. First-line anti-PD-L1 ICIs combined with chemotherapy are effective and safe for male extensive-stage SCLC patients. Further therapeutic strategies may need to be developed for patients with unfavorable outcomes (e.g., baseline high NLR and serum LDH level).

MS18.02 Treatment of Elderly Patients with SCLC

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

BackgroundThoracic radiotherapy (TRT) had been shown to improve overall survival (OS) in extensive-stage small cell lung cancer (ES-SCLC) patients. However, approximately one fourth of SCLC harbored baseline brain metastases (BMs) and were excluded from previous TRT trials. Thus, the role of TRT in this sub-cohort of ES-SCLC requires elucidation. In this study, we evaluated the efficacy of TRT in ES-SCLC patients with clinically controlled baseline BMs.MethodsIn this retrospective, multi-institutional cohort study, 49 patients fully staged as ES-SCLC with baseline BM, had their disease controlled at all sites with no BM symptoms for three months since treatment initiation were included. The patients were allocated to TRT or no-TRT groups according to whether they received consolidative TRT before progression. Their baseline characteristics were compared using the χ2 test. OS was selected as the primary observational endpoint. Survival and the incidence of cumulative progression between the groups were compared using log-rank analysis, and the interaction between TRT and selected factors was assessed via Cox proportional hazard analysis. Subgroup analysis was performed in oligo-metastasis patients (defined as five or fewer metastatic lesions in two or fewer organs).ResultsSeventeen (34.7%) patients received TRT, with a median dose of 54 Gy. The failure pattern analysis revealed initial intrathoracic progression in 31.3% and 66.7% of patients in the TRT no-TRT groups, respectively. Also, the TRT group had a significantly longer OS than the no-TRT group [hazard ratio (HR) 0.426, P=0.011]. Clinical covariates including age, gender, performance status, smoking, metastatic state, response after chemotherapy, and TRT, were included in multivariate regression analysis. TRT remained significantly correlated with better OS (HR 0.430, P=0.029). Twenty-three (46.9%) patients had oligo-metastasis at baseline. Subgroup analyses showed that TRT was significantly correlated with better OS in oligo-metastatic patients but not in non-oligo metastatic patients.ConclusionsTRT improved the prognosis of select ES-SCLC patients with baseline BMs and should be considered in this sub-cohort, which has not been covered by previous randomized trials.

P48.10 Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons

Introduction Small cell lung cancer (SCLC) represents about 15% of all lung cancers. Extensive stage (ES) SCLC represents around 60% of diagnosed SCLC cancers. The median survival in untreated ES SCLC is 2 to 4 months and that of treated cases is 8 to 13 months. Aim and Objectives This retrospective analysis aims to find out the clinical outcome of patients with ES SCLC and the prognostic factors affecting their survival. Methods Details of patients registered in the department of radiation oncology from January 1, 2010 to September 30, 2019 were retrieved from the hospital records. This includes the demographic characteristics, treatment received, toxicity, and follow-up details. Results Two-hundred eighty-three patients were included. Median age of presentation was 62 years. Around 97.5% of patients were men. Smokers constitute 94% of all cases. About 86.9% (246 patients) of cases were not alive at the end of the study period. The median estimated overall survival (OS) was 7 months ± 0.47 (95% confidence interval [CI]: 6.026–7.974) and progression-free survival (PFS) was 5 months ± 0.535 (95% CI: 3.952–6.048). Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), hyponatremia, number of chemotherapy cycles, consolidative radiotherapy (RT) and prophylactic cranial irradiation (PCI) were found to have prognostic effect on OS. Smoking, ECOG PS, number of chemotherapy cycles, consolidative RT, and PCI were found to have prognostic effects on PFS. Conclusion There is a difference in OS and PFS patterns of ES SCLC patients among various Indian studies even though the available data is scarce. Our study shows that the OS and PFS of our study population are comparable to other South Indian studies available. PS, serum sodium level, number of chemotherapy cycles, consolidative RT, and PCI were found to be independent prognostic factors for survival of ES SCLC. The identification of these factors will help physicians to tailor treatment.

PC 02.01 Thoracic Radiation - YES

Prophylactic cranial irradiation (PCI) is a companion treatment option for small cell lung cancer (SCLC) patients. However, its efficacy and associated risk factors have not been clearly defined. In this study, the authors aimed to systematically assess the effectiveness and role of PCI in the treatment plan of SCLC. The PubMed, Scopus, Web of Science, and Cochrane databases were searched using the following key terms and their equivalents: "brain," "radiotherapy," "metastases," "prophylactic," and "small cell lung cancer." Studies comparing overall survival (OS), progression-free survival (PFS), brain metastasis-free survival (BMFS), and incidence of brain metastases between patients receiving PCI and those not receiving it were considered eligible. Risk of bias was assessed using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) tool. Meta-analysis was conducted on the mentioned outcomes with subgrouping based on different factors. The authors identified 74 studies published between 1983 and 2022 with 31,551 SCLC patients, of whom 26.7% received PCI. The studies were a mix of prospective randomized and retrospective observational studies. Patients with limited-stage disease receiving PCI had better OS, PFS, and BMFS than those not receiving PCI. Patients receiving PCI also had significantly longer OS times and developed brain metastases significantly later. However, findings regarding extensive-stage SCLC were not as promising. PCI is an effective option for limited-stage SCLC patients. It improves OS and PFS, delays brain metastases, and reduces the incidence of brain metastases. However, it might not benefit patients with extensive-stage SCLC under adequate follow-up with MRI surveillance. Finally, the heterogeneity of the included studies and publication bias were the main limitations of this study.

BackgroundThis study aimed to identify shared and distinct prognostic factors related to organ-specific metastases (liver, lung, bone, and brain) in extensive-stage small cell lung cancer (ES-SCLC) patients, then construct nomograms for survival prediction.MethodsPatient data for ES-SCLC were from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2019. Kaplan–Meier analysis was applied to estimate overall survival (OS), and Cox regression was used to identify prognostic factors. A Venn diagram was utilized to distinguish common and unique prognostic factors among the variables assessed. These identified prognostic factors were used to formulate a nomogram, and its predictive accuracy and reliability were evaluated using C-indexes, calibration curves, and receiver operating characteristic (ROC) curves.ResultsA total of 24,507 patients diagnosed with ES-SCLC exhibiting metastases to the liver, lung, bone, and brain were included. The 6-month, 1-year, and 2-year OS rates were 46.1%, 19.7%, and 5.0%, respectively. Patients with liver metastasis demonstrated the most unfavorable prognosis, with a 1-year OS rate of 14.5%, while those with brain metastasis had a significantly better prognosis with a 1-year OS rate of 21.6%. The study identified seven common factors associated with a poor prognosis in ES-SCLC patients with organ-specific metastases: older age, male sex, unmarried status, higher T stage, presence of other metastases, and combination radiotherapy and chemotherapy. Furthermore, specific prognostic factors were identified for patients with metastasis to the liver, bone, and brain, including paired tumors, lack of surgical treatment at the primary site, and household income, respectively. To facilitate prognostic predictions, four nomograms were developed and subsequently validated. The performance of these nomograms was assessed using calibration curves, C-indexes, and the area under the curve (AUC), all of which consistently indicated good predictive accuracy and reliability.ConclusionsPatients diagnosed with ES-SCLC with organ-specific metastases revealed shared and distinct prognostic factors. The nomograms developed from these factors demonstrated good performance and can serve valuable clinical tools to predict the prognosis of ES-SCLC patients with organ-specific metastases.