Extensive-disease Small-cell Lung Cancer Patients Research Articles

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer.

The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited. We retrospectively assessed the real-world efficacy and safety of atezolizumab in addition to carboplatin and etoposide (EP + A), versus carboplatin and etoposide (EP) alone in previously untreated ED-SCLC patients. From a total of 99 patients, 46 were assigned to the EP + A group, and 53 to the EP group. No significant difference was observed in progression-free survival between the groups. However, the overall survival (OS) was significantly longer in the EP + A group (20.8 vs 12.1months; HR: 0.52; p = 0.0127). Patients older than 70years, male, with performance status 0-1, without liver metastasis, and low levels of C-reactive protein and neutrophil-lymphocyte ratio, experienced longer OS in the EP + A group compared to the EP group. The addition of atezolizumab to the platinum doublet regimen significantly extended OS in ED-SCLC patients, particularly among certain subgroups, suggesting its potential value in personalized treatment strategies. Further investigation is warranted to validate these findings.

Relationship between immune-related adverse events and treatment effectiveness in extensive disease small cell lung cancer.

This study aimed to assess the relationship between immune response adverse events (irAEs) and treatment efficacy in patients with extensive disease small cell lung cancer (ED-SCLC). We retrospectively evaluated the clinical effects in 40 ED-SCLC patients who had received immune-checkpoint inhibitors (ICIs), platinum agents, and etoposide between September 2019 and September 2021. We identified and compared patients belonging to two groups: irAE and non-irAE. Fifteen patients experienced irAEs, and 25 did not. The median progression-free survival in patients with irAE was longer than that in patients without irAE (12.6 months [95% CI: 6.3-19.3 months] vs. 7.2 months [95% CI: 5.8-7.9 months], p = 0.0108). However, the median overall survival (OS) was similar between irAE and non-irAE groups (27.6 months [95% CI: 15.4-NA] vs. 24.9 months [95% CI: 13.7-NA], p = 0.268). Seven (46.7%) in the irAE group and 20 (80%) in the non-irAE group received sequential therapy. The median OS was prolonged in patients who received first- and second-line therapy than in those who received first-line therapy alone (27.6 months [95% CI: 19.2-NA] vs. 6.6 months [95% CI: 0.3-NA], p = 0.053). Grade ≧ 3 irAEs occurred in five (12.5%) patients. Among them, grade 5 irAEs were observed in two patients, including exacerbation of polymyositis and pulmonary arterial embolism. In this study, the development of irAEs did not affect OS in patients with ED-SCLC who received platinum-based agents, etoposide, or ICI therapy. We determined that managing irAEs and administering first- and second-line therapies could contribute to prolonged OS.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years

BackgroundPoor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients.MethodsThis retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed.ResultsThe median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062–2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262–1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530–5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003).ConclusionsIn this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Protocol of the TREASURE study: Thoracic RadiothErapy with Atezolizumab in Small cell lUng canceR Extensive disease – a randomized, open-label, multicenter phase II trial

BackgroundRecently, the combination of the programmed death-ligand 1 (PD-L1) inhibitor atezolizumab with first-line chemotherapy has demonstrated to improve outcome for patients with advanced small cell lung cancer (SCLC), leading to approval of this regimen. At the same time, accumulating (pre-)clinical data suggest synergisms of radiotherapy and immunotherapy via the radiation-mediated induction of anti-tumor immunogenicity. Combining the recent findings, the TREASURE trial aims at further enhancing response to upfront chemo-immunotherapy by the addition of thoracic radiotherapy (TRT).Methods/designThe TREASURE trial is a randomized, multicenter, phase II clinical trial (ClinicalTrials.gov identifier, NCT04462276). One hundred four patients suffering from extensive disease (ED) SCLC, with any response to the standard of care induction chemo-immunotherapy will be randomized to receive atezolizumab maintenance therapy with or without TRT. The primary endpoint of this study is overall survival (OS). Secondary endpoints include further measures of efficacy, safety, and the collection of biomarker samples. A safety interim analysis will take place after n = 23 patients receiving TRT have been observed for three months after the end of TRT.DiscussionThis trial will investigate whether treatment efficacy can be improved by adding TRT to atezolizumab maintenance therapy in ED SCLC patients with any response after chemo-immunotherapy. Safety and feasibility of such a regimen will be evaluated, and biomaterials for a translational research project will be collected. Together, the results of this trial will deepen our comprehension of how checkpoint inhibition and radiotherapy interact and contribute to the evolving landscape of SCLC therapy.Trial registrationClinicaltrials.gov identifier: NCT04462276 (Date of initial registration: 8th July 2020), https://clinicaltrials.gov/ct2/show/NCT04462276Eudra-CT Number: 2019-003916-29 (Date of initial registration: 30th March 2020), https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-003916-29/DE

Long-term outcomes in extensive disease small cell lung cancer patients treated without immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) combined with chemotherapy have been approved as first-line treatment for patients with untreated extensive disease-small cell lung cancer (ED-SCLC). However, there are few reports about the long-term outcomes in patients with ED-SCLC treated without ICIs. Thus, we analyzed the long-term outcomes in patients with ED-SCLC. We retrospectively examined the medical records of patients with SCLC who were treated at our hospital between September 2002 and September 2019. The main inclusion criteria were as follows: (i) histological or cytological confirmation of SCLC, (ii) diagnosed with ED-SCLC and (iii) received chemotherapy, not including ICIs, as the first-line treatment. To assess the trends of treatment outcomes, we compared the survival outcomes between 2002-2010 (early) and 2011-2019 (late) groups. A total of 314 patients were included in this study. Patient characteristics at the time of first-line treatment were as follows: median age was 69years; 82% of the patients were male and 70% had a performance status of 0 or 1. The median follow-up time of overall survival (OS) was 7.4years, and 89% of the patients died. The median progression-free survival and survival time were 4.9 and 12.1months, respectively. Five-year survival rate was 2%. There was no significant difference in survival between the early and late groups. We found that the long-term outcomes in ED-SCLC patients treated without ICIs were poor. Prior to the approval of ICI treatment for ED-SCLC, there was no improvement in the OS for ~20years.

Effectiveness and safety of bevacizumab in extensive-disease small cell lung cancer: a systemic review and meta-analysis

BackgroundSmall cell lung cancer (SCLC) is highly invasive and poorly prognostic. The effects of chemotherapy with bevacizumab are promising on other tumors but unclear in extensive-disease SCLC (ED-SCLC). A systemic review and meta-analysis were performed to investigate the efficacy and toxicity in ED-SCLC patients.MethodsA review of current studies was performed on electronic databases and other sources to identify publications of ED-SCLC patients who received bevacizumab. Endpoints included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and complications.ResultsNine relevant articles with six single-arm and three two-arm studies were identified. Four hundred seventy-six patients were included, of which 368 and 108 were untreated and relapse patients. Most patients were performance status 0–1 (71.6%) and male (58.1%). The comparisons showed CT/bevacizumab slightly prolonged OS (HR =0.84) but significantly improved PFS (HR =0.74). The ORRs of untreated and relapse patients were 71% and 19%, though no significant difference was observed than CT/placebo. The most grade 3–4 complication and bevacizumab-associated complications were neutropenia and hypertension, whose rates were 33% and 6%. Patients who received CT/bevacizumab had a higher hypertension rate than CT/placebo (6% vs. 2%). No different complication rate was observed between high and lose dose groups.DiscussionThe present study suggests that bevacizumab in the combination of standard chemotherapy provides better PFS than chemotherapy alone. Although the combined regimen is well-tolerated, no superiority in OS or response rate is observed.

PCN59 Health Utility Values in Small Cell Lung Cancer: A Literature Review

Small cell lung cancer (SCLC) constitutes substantial disease burden with significant negative impact on survival and quality-of-life. Health state utilities are essential in economic evaluation and vary significantly across the countries. Given the scarce data on health utility score (HUS) for SCLC, the current literature review assessed the utility values in SCLC. An extensive literature search was conducted on EMBASE, MEDLINE (via-Ovid), and Cochrane Library by combination of Emtree/MeSH terms and keywords from inception to 07-January-2021. Bibliography of included studies and web searches were also conducted for additional publications. Studies investigating the HUS in SCLC were included. The quality assessment was performed by Cochrane-risk-of-bias tool and Newcastle-Ottawa-Scale. 10 studies were included after a comprehensive review of 527 citations. Majority of the studies used EQ-5D to estimate the HUS. The HUS at the start of first-line (1L), and second-line was 0.70 and at third-line 0.76 for patients with extensive disease SCLC (ED-SCLC) receiving care in US community oncology centers. HUS was higher (indicates better health state) for ED-SCLC patients on chemotherapy with stable disease (0.72 vs. 0.69 vs. 0.76) compared with progressive disease (0.52 vs. 0.37 vs. 0.53) for Canada, UK, and US, respectively. In Taiwan, HUS was higher in limited stage SCLC patients (0.87) than ED-SCLC (0.84) in younger (<65-years) but no difference in older (≥65-years) patients with limited (0.84) and extensive stage SCLC (0.84). HUS for ED-SCLC patients receiving 1L Atezolizumab+Carboplatin+Etoposide were higher than Carboplatin+Etoposide alone and the estimates were 0.736 vs. 0.723, 0.770 vs. 0.757, 0.730 vs. 0.725, 0.755 vs 0.750, 0.748 vs. 0.739 and 0.762 vs. 0.756 for Australia, Canada, France, Netherlands, UK and USA, respectively. Progressive ED-SCLC patients had worse HUS than patients with stable ED-SCLC. This literature review provides the health utility data to perform economic evaluation for Health Technology Assessment for SCLC.

History of Extensive Disease Small Cell Lung Cancer Treatment: Time to Raise the Bar? A Review of the Literature.

Simple SummarySmall cell lung cancer (SCLC) remains the most aggressive form of neuroendocrine tumor of the lung, for which treatment options remain limited. The introduction of immune checkpoint inhibitors has modified for the first time the therapeutic strategies in patients with extensive disease after decades. New therapeutic approaches are required. Deeper knowledge of tumor biology is required to gain new insights into this complex disease.Several trials have tried for decades to improve the outcome of extensive disease small cell lung cancer (ED-SCLC) through attempts to modify the standard treatments. Nevertheless, platinum/etoposide combination and topotecan have remained respectively the first and the second line standard treatments for the last 40 years. With the advent of immunotherapy, this scenario has finally changed. Our review aims to provide an overview of the primary studies on the actual therapeutic strategies available for ED-SCLC patients, and to highlight emerging evidence supporting the use of immunotherapy in SCLC patients.

Prognostic Value of Pretreatment Albumin-to-Alkaline Phosphatase Ratio in Extensive-Disease Small-Cell Lung Cancer: A Retrospective Cohort Study.

PurposeEvidence regarding the relationship between albumin-to-alkaline phosphatase ratio (AAPR) and overall survival (OS) in extensive-disease small-cell lung cancer (ED-SCLC) patients is limited. This study aimed to investigate whether AAPR was independently related to OS in ED-SCLC patients after adjusting for potential covariates.Patients and MethodsThis was a retrospective cohort study of 224 patients with ED-SCLC. The target independent and dependent variables were pretreatment AAPR and OS, respectively. Covariates included age; sex; Eastern Cooperative Oncology performance status score; smoking history; existence of metastasis to organs such as the bone, lung, liver, brain, malignant plural effusion and others; sum of organ metastasis (≤3, >3), evaluation of first-line treatment; and sum of treatment lines (<2, ≥2). Student’s t test or chi-squared test was used to analyze the associations between AAPR and clinical characteristics. Kaplan–Meier survival analysis and Cox’s proportional hazards regression model were used to assess the prognostic value of AAPR for OS.ResultsThe average patient age was 60.51±8.73 years, and 87.95% were men. A non-linear relationship between AAPR and OS was detected, with an inflection point of 0.35. The hazard ratios (HRs) of the left (AAPR <0.35) and right sides (AAPR ≥0.35) of inflection point were 0.04 (95% CI=0.00–0.70, p=0.0268) and 0.52 (95% CI=0.16–1.64, p=0.2659), respectively. Kaplan–Meier analysis showed a median OS of 9.73 months (95% CI=8.6–12.33) for AAPR <0.35 and 13.7 months (95% CI=11.43–16.37) for AAPR ≥0.35 (log-rank p<0.0001). The Cox proportional hazards model showed that AAPR <0.35 increased the risk of death after adjusting for potential confounders (HR=1.65, 95% CI=1.11–2.46). In subgroup analysis, the trends of HRs were increased across all subgroups with AAPR <0.35 after stratification.ConclusionPretreatment AAPR might be served as an independent prognostic indicator in ED-SCLC patients. Our findings should be further validated in large-scale and prospective clinical trials.

Treatment patterns and survival outcomes for small-cell lung cancer patients – a Swedish single center cohort study

Objectives: This real-world study on small-cell lung cancer (SCLC) patients aimed to investigate treatment patterns, outcome of re-challenge with platinum doublet chemotherapy (PDCT), and associations between clinical characteristics and survival outcomes.Material and methods: This retrospective single center cohort study was based on patients diagnosed with SCLC between 2008 and 2016 at the Karolinska University Hospital, Stockholm, Sweden. Patients were divided into two subgroups; limited disease (LD), receiving concomitant chemo- and radiotherapy and extensive disease (ED), receiving palliative PDCT. The progression-free survival (PFS) was defined as the interval between the start of CT and the earliest date of documented progression. ‘Refractory relapse’ (Rr) and ‘Sensitive relapse’ (Sr) were defined as relapse occurring < or ≥180 days after start of PDCT, respectively. The results for treatment patterns were reported as numbers and percentages of patients, and descriptive analyses including medians and 95% confidence intervals (CIs). The Cox proportional hazards regression model was applied to assess the relationship between clinical characteristics and overall survival (OS).Results: The study included 544 patients; 408 with ED and 136 patients had LD. The median PFS and OS for ED patients were 5.1 and 7.0, respectively. In the ED subgroup, Sr occurred in 169 patients (41%), with a longer median OS when compared to Rr patients (10.8 vs. 3.6 months). Patients with LD had a median PFS and OS of 12 and 24 months, respectively. Some LD patients did not show a sign of relapse (22%). The majority of LD patients who relapsed had Sr (66%), with a longer median OS when compared to patients with Rr (20.9 vs. 7.8 mo).Conclusions: The survival outcomes for ED and LD SCLC patients correspond to historical data. Patients with Sr after 1st line therapy might benefit from re-challenge with PDCT in the 2nd line setting.

Can consolidative thoracic radiotherapy improve outcomes in extensive-disease small cell lung cancer after chemotherapy with complete/near-complete responders?

In extensive-disease-small cell lung cancer (ED-SCLC), the median survival is 8-10 months and 2-year survival is <5%. Primary tumor progression occurs in 90% of patients approximately within 1 year. The role of consolidative thoracic radiotherapy (C-TRT) for the postchemotherapy residue with the aim of improving local control (LC) and survival is currently of great interest. The objective of this study is to determine the effectiveness of C-TRT on LC, progression-free survival (PFS), and overall survival (OS) in ED-SCLC. Medical records of patients diagnosed as SCLC between January 2010 and December 2015 were evaluated retrospectively. Patients who received C-TRT were identified. Pre- and post-chemotherapy radiological evaluations, radiotherapy schedules, relapse patterns, toxicity incidence, LC, PFS, and OS were analyzed. Among 552 SCLC patients, 26 ED-SCLC patients who underwent C-TRT were analyzed. Median follow-up was 7.5 months (range, 6.5-8.5 months). Nearly 50% of the patients had >4 metastatic lesions. Restaging was performed mostly by positron emission tomography/computed tomography and cranial magnetic resonance imaging. All patients had complete or near-complete response distantly. C-TRT was 10 × 300 cGy (n = 1), 23 × 200 cGy (n = 2), 25 × 200 cGy (n = 7), 30 × 200 cGy (n = 12), and 33 × 200 cGy (n = 4). There was no toxicity ≥ Grade 3. LC rate was 77%; there was no isolated local relapse. PFS was 3 months. Median survival was 13 months. The 1- and 2-year OS rates were 62% and 8%, respectively. In ED-SCLC patients, C-TRT may prevent isolated local recurrence and may improve 1-year survival. This survival improvement might be the reflection of high intrathoracic control achieved in 77% of patients.

Sarcopenia and Visceral Adiposity Are Not Independent Prognostic Markers for Extensive Disease of Small-Cell Lung Cancer: A Single-Centered Retrospective Cohort Study.

BackgroundSarcopenia and visceral adiposity have been suggested to affect prognosis and treatment efficacy in various types of cancers. The aim of our study was to evaluate whether pretreatment sarcopenia and visceral adiposity are associated with prognosis in patients with extensive-disease small-cell lung cancer (ED-SCLC).MethodsBetween September 2007 and March 2018, 128 ED-SCLC patients received first-line and platinum-based chemotherapy at our hospital. Based on pretreatment body mass index (BMI), psoas muscle index (PMI), intramuscular adipose tissue content (IMAC) and visceral-to-subcutaneous fat ratio (VSR) at lumbar vertebra L3 level, we divided these patients into two groups, and then compared overall survival (OS) and progression-free survival (PFS). Adjusted by age, serum albumin, lactate dehydrogenase (LDH), clinical stage and performance status, we detected independent prognostic factors by multivariate Cox proportional hazard analyses.ResultsWe did not find any significant differences in OS and PFS between two groups divided by BMI, PMI, IMAC and VSR. According to multivariate analyses, none of BMI, PMI, IMAC and VSR was an independent prognostic factor of OS and PFS.ConclusionsNeither pretreatment sarcopenia nor visceral adiposity is a prognostic marker of patients with ED-SCLC treated with standard regimen of platinum-based chemotherapy.

Prognostic value of 18F-FDG PET/CT metabolic parameters in small cell lung cancer

ObjectiveTo compare the prognostic values of metabolic parameters from pretreatment PET/CT between limited disease (LD) and extensive disease (ED) small cell lung cancer (SCLC) patients.MethodsData on 118 newly diagnosed SCLC patients (50 LD and 68 ED) who underwent pretreatment positron emission tomography–computed tomography (PET/CT) were reviewed. For PET, metabolic parameters were measured for: (1) primary tumor, maximum standardized uptake value (SUVmax), metabolic tumor volume, and total lesion glycolysis; and (2) all tumor lesions, SUVmax of the hottest tumor, whole body metabolic tumor volume (WBMTV), and whole body total lesion glycolysis (WBTLG). Prognostic values of metabolic parameters and other clinical variables were analyzed to predict overall survival (OS).ResultsIn LD, SUVmax of the primary tumor was an independent prognostic factor for OS. Patients with high SUVmax showed significantly worse OS than those with low SUVmax. In ED, WBMTV and WBTLG were independent prognostic factors for OS. Patients with high WBMTV or WBTLG showed significantly worse OS than those with low WBMTV or WBTLG.ConclusionsSUVmax of primary tumor was the only independent prognostic factor for OS in LD SCLC patients. WBMTV and WBTLG were independent prognostic factors in ED SCLC patients.

Prophylactic cranial irradiation in extensive disease small cell lung cancer: An endless debate.

Extensive disease Small cell lung cancer (ED-SCLC) represents a very aggressive malignancy in which brain metastases (BM) are quite common. Clinical trials on prophylactic cranial irradiation (PCI) have showed a clear decrease in the risk of developing BM but conflicting results concerning a possible survival advantage. A landmark European Organisation for Research and Treatment of Cancer (EORTC) prospective trial, as well as multitude of retrospective series confirm survival benefit after PCI. Recently, a Japan Clinical Oncology Group (JCOG) study did not find such survival benefit, provided that non-irradiated patients are closely followed by MRI. Henceforth, the role of PCI in this population has been questioned, on the ground of the possible absence of survival benefit, leading to a gradual shift in oncology practice. We performed a review of the literature on the subject of PCI in ED-SCLC patients. We conclude that PCI could still play a crucial role in these patients, considering not only a possible survival benefit, but also alternative endpoints, such as improved local control, delay in the onset of symptomatic BM and lower toxicity of a prophylactic- rather than an eventual active-intent treatment. Individualized attitude should be discussed with patients, while addressing all arguments in favour and against PCI.

Trends in Small-Cell Lung Cancer Survival in 1993-2006 Based on Population-Based Cancer Registry Data in Japan.

BackgroundLung cancers are classified into small-cell lung cancer (SCLC) and non-small-cell lung cancer due to their different treatment and prognosis. Although many studies have reported the specific survival of SCLC patients treated at cancer hospitals, survival from population-based data has rarely been reported.MethodsWe analyzed survival of SCLC cases diagnosed from 1993 through 2006 from a population-based cancer registry of six prefectures. To assess trends in SCLC survival, we defined three periods that mirrored developments in SCLC treatment: period 1, 1993–1998; period 2, 1999–2001; and period 3, 2002–2006. Assessments were based on relative survival (RS), excess hazard, and conditional survival.ResultsA total of 10,911 SCLC patients were analyzed. Five-year RS among limited disease SCLC (LD-SCLC) in periods 1 to 3 was 16.8%, 21.1%, and 21.4%, respectively. Five-year RS among extensive disease SCLC (ED-SCLC) in periods 1 to 3 was 2.3%, 2.8%, and 2.7%, respectively. Improvement in 5-year RS in periods 2 and 3 compared with period 1 was significant among both LD- and ED-SCLC patients (all P < 0.001). Conditional 5-year RS of LD-SCLC increased from 21% at year 0 to 73% at year 5, while that of ED-SCLC was 3% at year 0 and 53% at year 5.ConclusionsThe prognosis of SCLC patients improved from 1999–2001 but plateaued in 2002–2006, after which no further significant improvement was seen. Continuous survey based on population-based data is helpful in monitoring the impact of developments in treatment.

Radiotherapy improves the survival of patients with extensive-disease small-cell lung cancer: a propensity score matched analysis of Surveillance, Epidemiology, and End Results database.

BackgroundThe survival advantage of radiotherapy for patients with extensive-disease small-cell lung cancer (ED-SCLC) has not been adequately evaluated.MethodsWe analyzed stage IV SCLC patients enrolled from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 and December 2012. Propensity score analysis with 1:1 matching was performed to ensure well-balanced characteristics of all comparison groups. Kaplan–Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% CI.ResultsOverall, for all metastatic ED-SCLC, receiving radiotherapy was associated with both improved OS and CSS. Radiotherapy for thoracic lesion and any metastatic sites could significantly improve the OS and CSS, except for brain metastasis. For M1a-SCLC patient, radiotherapy, most likely to the primary site, significantly improved the survival (P<0.001). Furthermore, for those ED-SCLC patients with ≥ 2 metastatic sites, that is, polymetastatic ED-SCLC patients, radiation also significantly improved the median OS from 6.0 to 8.0 months (P=0.015) and the median CSS from 7.0 to 8.0 months (P=0.020).ConclusionThe large SEER results support that radiotherapy in addition to chemotherapy might improve the survival of patients with metastatic ED-SCLC.

P1.12-04 A Ph3 Study of Niraparib as Maintenance Therapy in 1L Platinum Responsive Extensive Disease Small Cell Lung Cancer Patients

Small cell lung cancer (SCLC) accounts for 15% of lung cancer, characterized by early dissemination and rapid development of chemo-resistant disease after platinum response (60-80%). Less than 2% of extensive disease SCLC (ED-SCLC) patients survive 5 years. The bi-allelic loss or inactivation of TP53 and RB1 is common in SCLC, the poly(ADP-ribose) polymerase-1 (PARP-1), a critical DNA damage repair enzyme, is highly expressed in SCLC, and SCLC is sensitive to platinum based chemotherapy, suggesting that the defect in DNA damage repair pathways plays an important role in SCLC. ZL2306/ Niraparib is a highly selective PARP-1/2 inhibitor which was exclusively licensed for development in China by Zai Laboratory from TESARO. In SCLC PDX model, niraparib demonstrated anti-tumor activities as monotherapy. In addition, niraparib demonstrated promising tumor growth inhibition in maintenance post platinum treatment in platinum sensitive SCLC PDX models. Clinically, in phase III NOVA study, niraparib demonstrated clear clinical benefit as maintenance treatment by significantly extending progression free survival in all platinum-sensitive recurrent ovarian cancer patients regardless gBRCA or HRD status which led to the approval by FDA and EMA in ovarian cancer. It is suggested that niraparib maintenance therapy could provide potential clinical benefit in platinum responsive SCLC. ZL-2306-005 is a randomized double-blind multi-center phase 3 study to evaluate the efficacy and safety of niraparib versus placebo as maintenance therapy in ED-SCLC patients who have had responses to platinum based chemotherapy. Approximately 590 Chinese patients with histologically or cytologically confirmed ED-SCLC who have achieved either complete response or partial response to their platinum based chemotherapy to their newly diagnosed disease will be randomized (2:1) to 2 groups, receiving either ZL-2306 or placebo in ZL-2306-005 study. Patients need to complete 4 cycles of etoposide + cisplatin/ carboplatin. All patients will be stratified by gender, LDH level and history of prophylactic cranial irradiation. ZL-2306 will be started with 300mg PO QD for patients with a baseline body weight ≥77 kg and a baseline platelet count ≥150,000/μL, or 200 mg PO QD for patients with a baseline body weight <77 kg or a baseline platelet count <150,000/μL based on RADAR analysis in NOVA study. Patients will remain on treatment until disease progression or intolerable toxicity. The co-primary endpoints are PFS assessed by independent central radiologic review and OS; the secondary endpoints are PFS assessed by investigator, CFI, QoL, safety and tolerability. Section not applicable Section not applicable

83P Radiotherapy improves the survival of patients with extensive disease small cell lung cancer: A propensity matched analysis of surveillance, epidemiology and end results database

Background: The survival advantage of radiotherapy (RT) for patients with extensive disease small cell lung cancer (ED-SCLC) has not been adequately evaluated. Methods: We analyzed stage IV SCLC patients enrolled from a large data from the Surveillance, Epidemiology, and End Results (SEER) registry through January 2010 and January 2012. Propensity score (PS) analysis with 1:1 matching and the nearest neighbor matching method were performed to ensure well-balanced characteristics of all comparison groups. Kaplan-Meier and Cox proportional hazardous model were used to evaluate the overall survival (OS), cancer-specific survival (CSS), and corresponding 95% confidence interval (95%CI). Results: Overall, for all metastatic ED-SCLC, receiving radiotherapy was associated with both improved OS and CSS. Generally speaking, radiotherapy for thoracic lesion and any metastatic sites could significantly improve the OS and CSS, except for brain metastasis. Before PS matching, radiotherapy significantly improved the survival of ED-SCLC patients with metastasis to brain (OS, HR = 0.71, with 95% CI = 0.61–0.83), however, the OS improvement became insignificant after PS matching (OS, HR = 0.91, with 95% CI = 0.74–1.12). For those M1a-SCLC patients without pleural effusion, radiotherapy, most likely to the primary site, also significantly improved the survival (P < 0.001). Furthermore, for those ED-SCLC patients with ≥ 2 metastatic sites, i.e., poly-metastatic ED-SCLC patients, radiation significantly improved the median OS from 6.0 months to 8.0 months (P = 0.015) and the median CSS from 7.0 months to 8.0 months (P = 0.020). Conclusions: The results suport radiotherapy in addition to chemotherapy might improve the survival of patients with metastatic ED-SCLC in a PS-matched patient cohort from the large SEER database. Although it should be adequately studied in phase III trials, it is prudent to select patients for radiotherapy in metastatic ED-SCLC. Legal entity responsible for the study: Dr. Zhenming Fu, Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China Funding: National Science Foundation of China (NSFC) Disclosure: All authors have declared no conflicts of interest.

Modeling the relationship between baseline lactate dehydrogenase and prognosis in patients with extensive-disease small cell lung cancer: a retrospective cohort study.

Elevated pretreatment lactate dehydrogenase (LDH) has been reported to be associated with poor survival in small cell lung cancer (SCLC). The present study aimed to investigate the continuous relationship between baseline LDH level and survival in patients with extensive-disease SCLC (ED-SCLC). Data were retrospectively collected from Shanghai Health Information Network. Patients primarily diagnosed as ED-SCLC from April 2011 to August 2014 were eligible for our study. Patients' survival status was checked in March 2016. A multivariate Cox proportional hazard model was used to detect the association between baseline serum LDH and overall survival. The corresponding continuous relationship was analyzed by using natural spline functions in the Cox model. A total of 132 eligible ED-SCLC patients were analyzed. Elevated LDH at baseline was associated with poor survival (HR =1.92; 95% CI, 1.29-2.86). An increment of LDH would still raise the risk of death even in abnormal range. Among patients with elevated LDH, those who had relatively higher LDH levels (>370 U/L) would have a poorer prognosis than those with moderately elevated LDH levels (245-370 U/L; median survival time, 114 vs. 274 days; P value of log rank test, 0.007). LDH is a significant prognostic biomarker for ED-SCLC patients. The interpretation of continuous relationship between LDH and patients' survival can provide more accurate information for clinical practice.

Pazopanib maintenance after first-line etoposide and platinum chemotherapy in patients with extensive disease small-cell lung cancer: a multicentre, randomised, placebo-controlled Phase II study (KCSG-LU12-07)

Background:We investigated whether pazopanib maintenance following first-line chemotherapy would improve survival in patients with extensive disease small-cell lung cancer (ED-SCLC).Methods:This study is a randomised, placebo-controlled, phase II study that enroled ED-SCLC patients who had not progressed after four cycles of etoposide plus platinum therapy. Eligible patients were randomly assigned (1 : 1 ratio) to either placebo or pazopanib 800 mg per day until progression or unacceptable toxicity. The primary end point was progression-free survival (PFS).Results:97 patients were enroled and randomly assigned; 2 patients did not receive study drugs. In total, 95 patients received maintenance therapy (pazopanib, n=48; placebo, n=47) and were included in the analyses. Grade 3 toxicities for pazopanib maintenance were thrombocytopenia (10.4%, including one case with grade 4 toxicity), liver enzyme elevation (10.4%), fatigue (6.3%), and hypertension (6.3%). Median PFS was 3.7 months for pazopanib maintenance and 1.8 months for placebo (hazard ratio 0.44, 95% confidence interval: 0.29–0.69, P<0.0001).Conclusions:Pazopanib maintenance significantly prolonged PFS in patients with ED-SCLC. Given the toxicity profiles, however, relevant biomarkers to select patients for benefit from pazopanib should be further investigated.