Extensive-stage Small Cell Lung Cancer Research Articles

1550TiP Phase II, multicenter, randomized, open-label study of DS-7300 in patients (pts) with pre-treated extensive-stage small cell lung cancer (ES-SCLC)

ES-SCLC is highly aggressive and despite high response rates to first-line therapy, disease progression often occurs within 6 months. There are limited later-line therapeutic options for relapsed SCLC, indicating a significant unmet need for treatment with durable benefit in second line and beyond. B7 homolog 3 protein (B7-H3), a type 1 transmembrane protein in the B7 family, is overexpressed in many cancers, including SCLC, and correlated with poor prognosis. DS-7300 is a novel, antibody drug conjugate comprising a humanized anti-B7-H3 immunoglobulin G1 monoclonal antibody and potent topoisomerase I inhibitor payload (exatecan derivative, DXd) covalently linked by a stable tetrapeptide-based cleavable linker.

EP14.03-003 Phase I Study of Palliative Radiotherapy with Lurbinectedin in Patients with Extensive Stage Small Cell Lung Cancer

Outcomes for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain poor with few therapeutic options after progression on first-line chemoimmunotherapy. Recently, lurbinectedin, a novel transcription inhibitor and alkylating agent, demonstrated a favorable response rate, duration of response, and toxicity profile, leading to its accelerated FDA approval of its use in this population. ES-SCLC is distinguished by a propensity for rapid progression, such that palliative radiotherapy (RT) is often delivered with the intent of alleviating symptoms while minimizing interruptions of systemic therapy.

1538P Prognostic impact of leptin (LEP)-mediated meta-inflammation (MI) in patients (pts) receiving maintenance immunotherapy (IT) for extensive-stage small cell lung cancer (ES-SCLC)

Immune-checkpoint inhibitors (IT) combined with platinum-based chemotherapy (CT) have become the new standard-of-care in the treatment of extensive-stage SCLC (ES-SCLC), however little is known about the small – but not negligible – subset of pts that obtains long-term benefits. Adipokines-induced metabolic dysfunctions and MI have been related to enhanced responsiveness to IT in obese pts; however, their prognostic role in SCLC is currently controversial.

Clinical impact of amrubicin monotherapy in patients with relapsed small cell lung cancer: a multicenter retrospective study.

BackgroundTopoisomerase is an essential enzyme for deoxyribonucleic acid replication, and its inhibitors suppress tumor progression. Amrubicin, a topoisomerase II inhibitor, is mainly used in the second-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC). However, the impact of different types of topoisomerase inhibitors for first-line chemotherapy on the efficacy of amrubicin remains unclear. In the present study, we aimed to evaluate the efficacy of second-line amrubicin in patients with relapsed SCLC who were previously treated with platinum-based chemotherapy, including topoisomerase I and II inhibitors.MethodsThis study retrospectively analyzed patients with ES-SCLC who experienced recurrence and were treated with amrubicin at 22 institutions in Japan between April 2015 and November 2020. The progression-free survival of amrubicin monotherapy was investigated using the Kaplan-Meier method.ResultsA total of 320 patients were enrolled in this study, with 59 (18%) receiving platinum plus topoisomerase I inhibitor irinotecan and 261 (82%) receiving platinum plus topoisomerase II inhibitor etoposide as first-line treatment. The progression-free survival of amrubicin was significantly longer in the irinotecan group than in the etoposide group (3.2 vs. 2.5 months; P=0.034).ConclusionsThese results showed that different types of topoisomerase inhibitors could affect the efficacy of amrubicin monotherapy in the second-line treatment of patients with relapsed ES-SCLC.

EP14.04-002 The Impact of Response on Survival in Extensive-Stage Small-Cell Lung Cancer in the CASPIAN Study

Gains in overall and progression-free survival (OS, PFS) and a higher objective response rate were observed in the CASPIAN trial of patients with extensive-stage small-cell lung cancer who received durvalumab in combination with etoposide and platinum-based chemotherapy (D+EP) compared with EP alone. However, the extent to which response predicts long-term survival is unknown. We defined response/non-response at different landmark times and derived OS and PFS during follow-up after each landmark among D+EP and EP patients.

EP14.01-006 CeLEBrATE: Phase II trial of CarbopLatin, Etoposide, Bevacizumab and Atezolizumab in Patients with exTEnsive-Stage SCLC-GOIRC-01-2019

The addition of programmed-death ligand 1 (PD-L1) inhibition with atezolizumab or durvalumab to platinum-doublet chemotherapy is the new standard treatment for extensive-stage small-cell lung cancer (ES-SCLC) as it improved survival in phase III trials, raising overall survival rate at 1 year (1-year OS) from 35% to about 50%. The vascular endothelial growth factor (VEGF) sustains angiogenesis and has immunosuppressive effects. The phase II SALUTE and the phase III FARM6PMFJM trial, the latter lead by our GOIRC group, have shown safety and provided signals of activity of bevacizumab, an anti-angiogenic agent, added to platinum doublet chemotherapy in patients with ES-SCLC.

EP14.01-015 IMforte: A Phase III Study of Lurbinectedin and Atezolizumab Versus Atezolizumab as Maintenance Therapy in ES-SCLC

Despite the effectiveness of PD-L1 inhibitors in combination with platinum-based chemotherapy as first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC), most patients still have disease progression and prognosis remains poor. In the IMpower133 study, the addition of atezolizumab (monoclonal anti-PD-L1 antibody) to chemotherapy improved median overall survival (mOS) to 12.3 months compared with 10.3 months in the chemotherapy plus placebo arm (HR 0.70; 95% CI: 0.54, 0.91; P=0.007; Horn et al, 2018).

1541P Real-world data of atezolizumab plus carboplatin-etoposide for patients with extensive stage SCLC: The UK experience

The addition of atezolizumab to carboplatin/etoposide (A-CE) for patients with extensive stage SCLC (ES-SCLC) has been recently established as standard first-line treatment on the basis of the IMPOWER-133 trial. Unfortunately, efficacy and safety data of this combination in the real-world setting is lacking. We retrospectively evaluated consecutive patients with ES-SCLC treated with A-CE between January 2020 and September 2021 in eight centres in the UK. Clinical and pathological data was collected and analysed. A total of 192 patients were included. Baseline clinical characteristics are summarized in the table. One hundred forty seven (77,8%) patients received four cycles of A-CE; median number of doses of atezolizumab was 7 (range 1-20). Fifty-two (27%) patients also received prophylactic cranial irradiation and sixty-one (31,7%) consolidation thoracic radiotherapy. Seventy-six (39,6%) patients received at least one subsequent treatment. At a median follow-up of 15 months, median progression-free survival (PFS) and overall survival (OS) were 5,31 and 8,85 months, respectively. Overall response rate was 69,7%. The OS rates at 12 months and 18 months were 38,25% and 20,36%, respectively. Treatment-related adverse events led to discontinuation of treatment in 32 patients (16,7%).Table: 1541PMedian age – years (range)66 (35-83)Sex – no. (%)MaleFemale83 (43,2)109 (56,8)Smoking status NeverCurrentFormerUnknown9 (4,7)50 (26,0)116 (60,4)17 (8,8)ECOG performance status score – no. (%)012330 (17)140 (73)21 (11)1 (0,5)Stage (TNM 8th edition) – no. (%)IIIIV14 (7,3)178 (93)Concomitant autoimmune disease – no. (%) Brain metastasis – no. (%)12 (6) 29 (15) Open table in a new tab Data from our series show comparable PFS but inferior OS than those reported in the trial. Known negative prognostic factors were more common in our cohort of patients at baseline and may have determined a shorter OS. Real-world data in this setting could help to optimise clinical management of these patients.

EP14.05-002 Impact of Body Mass Index on Survival in Patients with Small Cell Lung Cancer

Small-cell lung cancer (SCLC), accounts for approximately 13% of lung cancers. Despite recent advances in first line treatment, SCLC still represents a disease with a dismal prognosis. Previous studies in patients with non-SCLC (NSCLC) treated with immunotherapy, identified baseline Body Mass Index (BMI) as a surrogate marker of treatment benefit. We sought to determine whether baseline BMI had in impact in overall survival (OS) in patients with limited and extensive stage SCLC.

1532P Phase IIIb study of durvalumab plus platinum-etoposide in first-line treatment of extensive-stage small cell lung cancer (CANTABRICO): Preliminary efficacy results

Most patients (Pts) with small-cell lung cancer (SCLC) have extensive-stage (ES) disease at diagnosis, and poor prognosis. First-line durvalumab (D) plus platinum–etoposide (EP) significantly improved overall survival in pts with ES-SCLC versus control group in CASPIAN study. CANTABRICO will assess safety and effectiveness of D plus EP in a real world ES-SCLC population in Spain.

P2.10-03 High-dose Thoracic Radiotherapy Improves the Overall Survival of Oligo-Metastatic Extensive-Stage Small Cell Lung Cancer

The CREST trial reported consolidative thoracic radiotherapy (TRT) of 30 Gy in 10 fractions provided a 10% 2-year overall survival (OS) benefit in extensive-stage small cell lung cancer (ES-SCLC) with residual intrathoracic disease after standard chemotherapy. A secondary analysis of the CREST trial data indicated that more intensive TRT should be investigated. But follow-up studies regarding this topic were scarce. Therefore, we evaluated the efficacy of high-dose TRT in ES-SCLC patients from our institution.

1533P Atezolizumab (ATZ) plus carboplatin (Cb) and etoposide (eto) in patients with untreated extensive-stage small cell lung cancer (ES-SCLC): Results from the interim analysis of MAURIS trial

MAURIS is a multicenter, open label, single arm, phase IIIb trial conducted in 25 Italian centers, that evaluates the safety and efficacy of ATZ + Cb-Eto in patients with newly diagnosed ES-SCLC, according to the new standard of care from the pivotal trial IMpower133. Patients (pts) with ECOG PS2, untreated asymptomatic brain metastases (BM) were eligible for this study and consolidative and palliative radiotherapy was also allowed. An interim analysis (IA) has been conducted roughly one year from the end of enrolment with a median follow-up of 10.5 months. Patients enrolled in the study received ATZ 1200 mg + Cb-Eto every 3 weeks for 4–6 cycles in the induction phase, followed by ATZ maintenance every 3 weeks up to disease progression, unacceptable toxicity or clinical deterioration. The primary endpoints were the incidence of serious adverse events (SAE) and immune-mediated AEs (imAE). The secondary endpoints were 1 year survival, overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). 154 patients (95 males, mean age 65.1 years, 6 pts with PS2, 19 pts with BM) were treated. At data cut-off 28 oct 2021, 139 pts (90.3%) discontinued the treatment: 97 pts (63.0%) due to progressive disease, 17 pts (11.0%) due to AE. Safety data related to the induction phase and efficacy data at data cut-off were analysed overall and by the number of induction cycles.Table: 1533PInduction PhaseTotal n=154≤3 cycles n=224 cycles n=43≥5 cycles n=89Safety n (%)SAEs46 (29.9)14 (63.6)15 (34.9)17 (19.1)Treatment related SAE28 (18.2)6 (27.3)12 (27.9)10 (11.2)imAE23 (14.9)4 (18.2)5 (11.6)14 (15.7)Treatment related AE117 (76.0)13 (59.1)35 (81.4)69 (77.5)Treatment AE leading to death7 (4.5)6 (27.3)0 (0.0)1(1.1)Efficacy1 year survival, n (%)65 (41.9)0 (0.0)18 (41.9)47 (52.8)OS (mo), median (95% CI)10.7 (9.9-13.7)2.7 (1.0-7.6)10.4 (8.6-14.2)13.8 (10.7-18.2)PFS (mo), median (95% CI)5.5 (5.3-5.8)1.8 (1.0-3.9)4.5 (4.1-5.5)5.8 (5.5-6.5)ORR, n (%)111 (71.6)5 (21.7)31 (72.1)75 (84.3) Open table in a new tab In this interim analysis, safety data observed in the induction phase seem consistent with IMpower133 results considering a patient population closer to clinical practice both for baseline patient characteristics and co-treatments allowed. In terms of efficacy data, we found that PFS and ORR were also aligned. Survival data in relation to the number of cycles in the induction phase, according to the investigator’s choice, might reflect a biased population and they should be confirmed.

1535P Efficacy and safety of amrubicin after treatment with immune checkpoint inhibitor combined with chemotherapy in extensive-stage small cell carcinoma: MiSSION1

Previous studies have shown that adding immune checkpoint inhibitor (ICI) to chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) is effective and is currently the first-line treatment. However, there is no evidence whether it is effective as a second-line treatment after first-line chemotherapy and ICI combination therapy. Amrubicin is recommended as a second-line treatment for ES-SCLC in the guideline, and it is frequently used in Japan. Here, we report a retrospective study on the efficacy and safety of amrubicin as a second-line treatment for ES-SCLC after ICI therapy.

1548P Identification of inflamed-phenotype of small cell lung cancer leading to the efficacy of anti-PD-L1 antibody and chemotherapy

Platinum etoposide plus anti-programmed cell death ligand-1 (PD-L1) antibody therapy is the standard of care for extensive-stage small cell lung cancer (ES-SCLC). However, patient characteristics associated with the efficacy of the combination therapy in SCLC are unclear.

EP14.05-010 Real-World Eligibility for Clinical Trials in Extensive Stage Small Cell Lung Cancer Patients

The IMpower 133 and CASPIAN trials showed a statistically significant survival benefit in extensive-stage small cell lung cancer (ES-SCLC) patients. However, clinical trials often have strict inclusion and exclusion criteria, which limits the generalizability of findings and can impact trial accrual in clinical practice. The current study evaluates the proportion of real-world patients who would have met eligibility for the IMpower 133 and CASPIAN trials and characterizes factors that would have impacted eligibility for these trials in the real-world setting.

1549TiP DeLLphi-303: Phase Ib first-line combination study of tarlatamab, a DLL3-targeting half-life extended bispecific T-cell engager (HLE BiTE®), with carboplatin, etoposide, and PD-L1 inhibition in extensive stage small cell lung cancer (ES-SCLC)

The inhibitory Notch ligand, delta-like ligand 3 (DLL3), is a compelling therapeutic target due to its aberrant expression on the cell surface in most small cell lung cancer (SCLC). Tarlatamab (AMG 757) is a half-life extended bispecific T-cell engager (HLE BiTE®) molecule designed to specifically bind DLL3 on target cancer cells and CD3 on T cells, resulting in T cell-dependent killing of tumor cells. Data from an ongoing first-in-human monotherapy study show acceptable safety with evidence of tarlatamab efficacy in patients with relapsed/refractory SCLC (NCT03319940).

EP14.05-009 LUMINANCE: A Phase IIIb Study of Durvalumab + Platinum-Etoposide for First-Line Treatment of Extensive-Stage SCLC (ES-SCLC)

Immune checkpoint inhibitors combined with chemotherapy have become standard-of-care first-line treatment for ES-SCLC in recent years. In the phase III CASPIAN study, the PD-L1 inhibitor durvalumab, in combination with platinum-etoposide (EP), demonstrated a statistically significant improvement in overall survival (OS) vs EP alone in first-line treatment of ES-SCLC (HR 0.73 [95% CI 0.59-0.91; p=0.0047]); OS benefit was sustained after >3 years median follow-up (HR 0.71 [95% CI 0.60‒0.86; nominal p=0.0003]).

MA01.08 Impact of [18F]FDG PET/CT-derived Metabolic Parameters on Outcomes in Extensive-stage SCLC

Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung cancer, accounting for 10-15% of all lung cancers, commonly classified in limited stage (LS-SCLC) and extensive stage (ES-SCLC). Despite the introduction of chemoimmunotherapy as new standard first-line therapy for ES-SCLC, the benefit of addition of the programmed-death ligand 1 (PD-L1) inhibitors is limited to a subset of patients, suggesting the importance of identifying predictive biomarkers of response. [18F]FDG-PET/CT is commonly used for the staging and therapeutic planning of SCLC patients.

EP14.05-020 Population-based Outcomes for Patients with Extensive-Stage Small-cell Lung Cancer from the Canadian SCLC Database (CASCADE)

Small cell lung cancer (SCLC) is an aggressive malignancy representing 15% of lung cancers. Approximately 2/3 of patients are diagnosed with extensive stage (ES) disease. Initial treatment involves platinum-based chemotherapy, with recent evidence supporting the addition of immunotherapy, followed in some cases by thoracic radiotherapy and/or prophylactic cranial irradiation (PCI). Despite high response rates to initial therapy, relapses are common and overall survival is poor. There is limited prospective evidence to guide 2nd line systemic therapy and beyond.

EP14.05-007 A Study of the Best Reduction in Target Lesion Size and Treatment Duration in the Durvalumab plus Platinum-Etoposide Regimen for ES-SCLC

Biomarker for the combination of chemotherapy and immune checkpoint inhibitor in extensive-stage small-cell lung cancer have not been identified at this time, and neither TC expression, IC expression, nor tTMB expression have been significant biomarkers in exploratory PD-L1 analysis of the CASPIAN study. Early identification of factors that would allow for long-term treatment duration of the durvalumab plus platinum-etoposide regimen is very important, and we focused on the best reduction from baseline in target lesion size.