Extensive Small Cell Lung Cancer Research Articles

Integration of clinical and blood parameters in risk prognostication for patients receiving immunochemotherapy for extensive stage small cell lung cancer: real-world data from two centers

BackgroundImmune checkpoint inhibitors (ICIs) had modest advances in the treatment of extensive-stage small cell lung cancer (ES-SCLC) in clinical trials, but there is a lack of biomarkers for prognosis in clinical practice.MethodsWe retrospectively collected data from ES-SCLC patients who received ICIs combined chemotherapy from two centers in China, integrated clinical and blood parameters, and constructed risk prognostication for immunochemotherapy. The population was divided into high- and low-risk groups, and the performance of the model was assessed separately in the training and validation cohorts.ResultsTwo hundred and twenty and 43 patients were included in the training and validation groups, respectively. The important predictors were screened including body mass index, liver metastases, coefficient variation of red blood cell distribution width, lactate dehydrogenase, albumin, and C-reactive protein. Predicting 1-year overall survival (OS), the AUC values under ROC for the model under training, internal validation, and external validation were 0.760, 0.732, and 0.722, respectively, and the calibration curve and clinical decision curve performed well. Applied the model to divide patients into low-risk and high-risk groups, and the median OS was 23.7 months and 9.1 months, and the median progression-free survival was 8.2 months and 4.8 months, respectively; furthermore, this ability to discriminate survival was also observed in the validation cohort.ConclusionsWe constructed a novel prognostic model for ES-SCLC to predict survival employing baseline tumor burden, nutritional and inflammatory parameters, it is easily measured to screen high-risk patient populations.

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

1802P Cost-effectiveness study of atezolizumab (ATZ) vs. durvalumab (DUR) in elderly extensive disease small cell lung cancer (ED-SCLC) patients (pts): Real-world data (RWD) on first-line chemotherapy combined with immune-checkpoint inhibitors (Chemo-ICIs)

1011: Thoracic radiotherapy and PCI in extensive stage small cell lung cancer following chemoimmunotherapy

1011: Thoracic radiotherapy and PCI in extensive stage small cell lung cancer following chemoimmunotherapy

Association Between Sarcopenia, Clinical Outcomes, and Survival in Patients with Extensive-Stage Small Cell Lung Cancer Treated with First-Line Immunochemotherapy: A Prospective Cohort Study.

To investigate the association between sarcopenia, short-term efficacy, and long-term survival in patients with extensive small-cell lung cancer (SCLC) treated with standard first-line immunochemotherapy. A total of 63 patients initially diagnosed with extensive-stage small cell lung cancer were enrolled in the prospective study from December 1, 2020 to December 31, 2022. The clinical characteristics, body composition, blood test results, and image data were obtained before treatment. Patients were divided into sarcopenia and non-sarcopenia groups according to the diagnostic criteria of the Asian Sarcopenia Working Group 2019. The primary outcome was overall survival (OS) and comprehensive survival analyses were performed. Secondary outcomes included short-term efficacy and adverse events associated with first-line immunochemotherapy. The median age of the 63 patients enrolled in our study was 63.0 years (40-80 years). The incidence of sarcopenia was 19.0% (12/63) in patients with extensive SCLC. Compared with non-sarcopenia patients, extensive-stage SCLC patients with sarcopenia were significantly older (69.0 vs. 62.0, P = 0.017), and had lower body mass index (BMI) (20.29 vs. 24.27, P < 0.001), hand grip strength (HGS) (20.42 vs. 30.75, P < 0.001), and albumin (35.9 vs. 41.40, P < 0.001). The objective response rate after two cycles of standard first-line immunochemotherapy in the sarcopenia group was lower than in the non-sarcopenia group (30.0 vs. 78.9%, P = 0.012). There was no significant difference in chemotherapy-related hematological toxicity between the two groups. During a median follow-up of 15 months (3-33 months), patients with extensive SCLC had a median OS of 24 months, with 1-year survival of 75% and 2-year survival of 52%, respectively. Compared to non-sarcopenia patients, the median OS in the sarcopenia group was significantly shorter (9 vs. 24 months, P = 0.0014). Multivariate Cox analysis showed that sarcopenia was an independent risk factor for OS in patients with extensive SCLC (HR = 4.993, 95%CI = 1.106-22.538, P = 0.037). Patients with Extensive SCLC and sarcopenia had worse clinical outcomes and shorter OS. Sarcopenia is a prognostic factor affecting first-line treatment efficacy and long-term survival of patients with SCLC in the era of immunotherapy.

Clinical efficacy and safety of immune checkpoint inhibitors plus anlotinib as secondline or subsequent therapy in extensive stage small cell lung cancer: a retrospective study.

Treatments are limited for extensive stage small cell lung cancer (ES-SCLC) patients in secondline or subsequent setting. This study aimed to explore the clinical efficacy and safety of immune checkpoint inhibitors (ICIs) plus anlotinib as secondline or subsequent therapy in ES-SCLC. We retrospectively analyzed 116 patients with ES-SCLC at Shandong Provincial Qianfoshan Hospital between January 2019 and March 2024. According to the different therapy regimes, they were divided into three groups, ICI plus anlotinib as secondline or subsequent therapy group (ICI + anlotinib group), single ICI as secondline or subsequent therapy group (single ICI therapy group), single chemotherapy as secondline therapy group (single chemotherapy group). Kaplan-Meier method was used to compare the progression-free survival (PFS) and the overall survival time (OS) among these three groups. Cox regression analysis was used to analyze different factors which correlated to PFS and OS. The adverse events were assessed according to the Common Terminology Criteria for Adverse Events version 5.0. Kaplan-Meier analysis showed that patients in ICI + anlotinib group had a longer PFS and OS compared to patients in single ICI therapy group (median PFS [mPFS]: 6.7months vs. 4.6months, P = 0.007; median OS [mOS]:12.4months vs. 8.4months, P = 0.041) and single chemotherapy group (mPFS: 6.7months vs. 3.0months, P < 0.001; mOS: 12.4months vs. 7.2months, P = 0.002). The Cox regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), liver metastasis, brain metastasis and treatment regimes were independent predictors that affecting the PFS and OS of all the enrolled patients. The common adverse events (AEs) were wleukopenia and fatigue. There was no significant statistical difference in other AEs among the three groups except for leukopenia. ICI + anlotinib as secondline or subsequent therapy has better efficacy than single ICI group and single chemotherapy group and with tolerable toxicities for patients with ES-SCLC.

Evaluation of the prognosis in patients with small-cell lung cancer treated by chemotherapy using tumor shrinkage rate-based radiomics

BackgroundSmall-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown.MethodsWe performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan–Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC.ResultsThe TSR cutoff was identified to be − 6.6%. Median PFS and OS were longer in the group with a TSR < –6.6% than in the group with a TSR ≥ − 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < − 6.6% than when it was > − 6.6%. Brain metastasis-free survival was better in the group with a TSR < − 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS.ConclusionsThe TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.

Efficacy of Apatinib Combined with Etoposide for Maintenance Therapy in Extensive Stage Small Cell Lung Cancer

Objective: To investigate the efficacy, safety and survival of apatinib combined with etoposide for maintenance therapy in extensive stage small cell lung cancer (ES-SCLC). Method: A total of 70 patients with extensive stage small cell lung cancer after standard chemo-radiotherapy who were admitted to Tangshan people’s Hospital from January 2019 to February 2023 were enrolled and then grouped into the observation group and the control group by random number table method, with 35 patients in each group. Patients from the observation group received apatinib combined with oral etoposide capsules for maintenance therapy. Patients from the control group received etoposide capsules for maintenance chemotherapy. The clinical efficacy and adverse reactions of these two groups were compared, and the 6-month and 1-year survivals were followed up. Results: The objective response rate (ORR) and disease control rate (ODC) of the observation group were higher than those of the control group [37.1% (13 / 35) vs. 17.1% (6 / 35), 65.7% (23 / 35) vs. 40% (14 / 35)], and the differences were statistically significant (all p&lt;0.05). There was no significant difference in the incidence of adverse reactions between these two groups (p&gt;0.05). The 6-month and 1-year survival rates of the observation group were significantly higher than those of the control group, and the differences were statistically significant (all p&lt;0.05). Conclusion: Apatinib combined with etoposide capsules applied for maintenance therapy in extensive stage small cell lung cancer could provide improved clinical efficacy and survival rate of patients, with tolerable adverse reactions.

DNA damage response signatures are associated with frontline chemotherapy response and routes of tumor evolution in extensive stage small cell lung cancer.

A hallmark of small cell lung cancer (SCLC) is its recalcitrance to therapy. While most SCLCs respond to frontline therapy, resistance inevitably develops. Identifying phenotypes potentiating chemoresistance and immune evasion is a crucial unmet need. Previous reports have linked upregulation of the DNA damage response (DDR) machinery to chemoresistance and immune evasion across cancers. However, it is unknown if SCLCs exhibit distinct DDR phenotypes. To study SCLC DDR phenotypes, we developed a new DDR gene analysis method and applied it to SCLC clinical samples, in vitro , and in vivo model systems. We then investigated how DDR regulation is associated with SCLC biology, chemotherapy response, and tumor evolution following therapy. Using multi-omic profiling, we demonstrate that SCLC tumors cluster into three DDR phenotypes with unique molecular features. Hallmarks of these DDR clusters include differential expression of DNA repair genes, increased replication stress, and heightened G2/M cell cycle arrest. SCLCs with elevated DDR phenotypes exhibit increased neuroendocrine features and decreased "inflamed" biomarkers, both within and across SCLC subtypes. Treatment naive DDR status identified SCLC patients with different responses to frontline chemotherapy. Tumors with initial DDR Intermediate and DDR High phenotypes demonstrated greater tendency for subtype switching and emergence of heterogeneous phenotypes following treatment. We establish that SCLC can be classified into one of three distinct, clinically relevant DDR clusters. Our data demonstrates that DDR status plays a key role in shaping SCLC phenotypes, chemotherapy response, and patterns of tumor evolution. Future work targeting DDR specific phenotypes will be instrumental in improving patient outcomes.

Advances in thoracic consolidation radiotherapy after first-line immunotherapy combined with chemotherapy for extensive stage small cell lung cancer

Small cell lung cancer (SCLC) accounts for about 13%~17% of primary bronchial lung cancer. Due to its rapid growth rate, aggressive behavior, early metastasis and poor prognosis, about 70% of patients were diagnosed with extensive-stage (ES) disease. Although most ES-SCLC patients are sensitive to initial chemotherapy, local recurrence and distant metastasis develop in the short term. Immunotherapy has brought the dawn to overcome it. At present, immune checkpoint inhibitor combined with chemotherapy has become an important strategy as first-line therapy for ES-SCLC. Nevertheless, patients are still at a high risk of chest lesion recurrence after initial systemic therapy. Whether the addition of thoracic consolidation radiotherapy (TRT) can reduce chest lesion recurrence rate remains to be determined. In this review, we summarized the latest research progress in the mode of first-line chemotherapy combined with immunotherapy followed by TRT in ES-SCLC, aiming to provide reference for clinical practice.

Tumor mutational burden adjusted by neutrophil-to-lymphocyte ratio serves as a potential biomarker for atezolizumab-treated patients with extensive stage small cell lung cancer

BackgroundThere is a desperate for the identification of more accurate and efficient biomarkers for ICI responses in patients with SCLC.MethodsThe data of our study was obtained from IMpower133 study. A total of 202 patients with SCLC received the treatment of placebo plus carboplatin plus etoposide (EC) while a total of 201 patients with SCLC received the treatment of atezolizumab plus EC. Overall survival (OS) was compared using Kaplan Meier analyses. Univariate and multivariate Cox regression analysis were used to determine independent prognostic variables affecting OS in patients with SCLC.ResultsWe have demonstrated that a higher TMB adjusted by a lower neutrophil-to-lymphocyte ratio (NLR) is significantly correlated with improved OS, in patients with SCLC subject to either atezolizumab or placebo (P = 0.001 for atezolizumab and P = 0.034 for placebo). Moreover, Cox model showed that TMB < 10 mut/Mb adjusted by NLR ≥ median was an independent factor of OS for atezolizumab-treated SCLC patients (hazard ratio [HR], 2.82; 95% confidence interval; 1.52–5.24; P = 0.001). Both univariate and multivariate cox regression analysis showed that for patients with SCLC harboring low NLR and high TMB, survival is significantly longer in those treated with atezolizumab than those treated with placebo. Survival benefit is significantly higher in atezolizumab-treated patients with SCLC than those treated with placebo (P = 0.018 for TMB cutoff = 10 mut/Mb, P = 0.034 for TMB cutoff = 16 mut/Mb).ConclusionOur findings provide a promising insight into the utility of NLR-adjusted TMB in the prognosis and immune responses in patients with SCLC.

Results of a phase III clinical trial with anti-PDL1 treatment in combination with chemotherapy for extensive stage small cell lung cancer.

8095 Background: In China, small cell lung cancer (SCLC) accounts for over 15% of lung cancers. The morbidity of SCLC has been continuously increasing. SCLC is invasive, fast-growing cancer that distinctly differs from other cancers. Approximately 70% of cases present with metastasis at diagnosis and the median overall survival rate is about 8 to 11 months with a 5-year survival rate of less than 5%. Although being sensitive to chemotherapy and radiotherapy, SCLC patients are liable to relapse and often present with drug resistance. Here we study the combination of Socazolimab, an anti-PDL1 antibody, carboplatin and etoposide to treat extensive stage small cell lung cancer. Methods: The study is a randomized, double-blinded, placebo-controlled multicenter Phase III clinical trial. Patients who have extensive-stage SCLC are eligible to the trial. Patients are randomly assigned to the study group (Socazolimab + carboplatin + etoposide) or control group (placebo + carboplatin + etoposide) at 1:1 ratio, with a treatment cycle of every 3 weeks. There are 4 cycles of chemotherapy followed by Socazolimab or placebo alone until termination events occurred or for up to 2 years. The primary endpoint is overall survival (OS). The major secondary endpoint is progression free survival (PFS). Results: There were a total of 498 patients recruited for the study with average age of 61.9 amount which 449 patients were diagnosed with stage IV SCLC. All the analysis was based on intent-to-treat (ITT). The median baseline performance status score was 1.0. The median OS of study group and control group are 13.90 months (95% CI: 12.22-15.34) and 11.58 months (95% CI: 10.64-12.81) respectively, with a P-value of 0.0316. The 24 month survival rate of study group and control group are 20.7% (95% CI:14.8-27.3) and 5.9 %(95% CI: 0.8-18.9). The median PFS of the two groups are 5.55 months (95% CI:5.06-5.82) and 4.37 months (95% CI: 4.27-4.70) with a P-value &lt; 0.0001. The treatment related adverse event were similar in both groups. Conclusions: These results show that Socazolimab plus chemotherapy continued to provide clinically meaningful improvements in OS for patients with extensive stage small cell lung cancer. Clinical trial information: NCT04878016 .

A phase II trial of monalizumab in combination with durvalumab (MEDI4736) plus platinum-based chemotherapy for first-line treatment of extensive stage small cell lung cancer (MOZART): Hoosier Cancer Research Network LUN21-530 study.

TPS8129 Background: Chemoimmunotherapy consisting of platinum, etoposide, and PD-L1 inhibitor remains the standard of care first-line treatment for extensive stage small cell lung cancer (SCLC) yielding median overall survival (OS) of slightly over a year. NKG2A/CD94 is an immune checkpoint that is selectively expressed on natural killer (NK) cells and CD8+ T cells in the tumor microenvironment. When engaging with its ligand, HLA-E, NKG2A transduces inhibitory signals that suppress immune-mediated cytotoxicity. Thus, NKG2A blockade enhances anti-tumor immunity by promoting both, NK and CD8+ T cell, effector functions. Monalizumab, a monoclonal antibody targeting NKG2A, enhances NK cell activity against tumor cells and rescues CD8+ T cell function in combination with PD-(L)1 axis blockade. Pre-clinical data have demonstrated that the absence of NK cells substantially enhances metastatic dissemination of SCLC tumor cells in vivo. NK cell function is modulated in response to cytotoxic chemotherapy, especially platinum. Post-chemotherapy NK cells display an induced expression of NKG2A compared with pre-chemotherapy patients and is associated with a reduced NK cell mediated anti-tumor activity. Hyperactivation of NK cell activity ameliorates SCLC metastases, an effect that is enhanced when combined with anti PD-(L)1 therapy. Altogether, these data suggest that addition of monalizumab to standard of care first-line treatment may be associated with improved efficacy in patients with SCLC. Methods: Patients with extensive-stage SCLC with ECOG performance status of 0-2 and adequate organ function are eligible for enrollment on this single-arm phase II study with an initial safety lead-in cohort. Patients may have received one prior cycle of platinum doublet with or without durvalumab and may have treated or untreated asymptomatic brain metastasis. Patients will receive platinum (cis or carbo), etoposide, durvalumab, and monalizumab every 3 weeks for 4 cycles followed by durvalumab and monalizumab every 4 weeks until disease progression or unacceptable toxicity. Primary endpoints include 1-year progression-free survival, safety, and tolerability. Secondary endpoints include objective response rate, 1-year overall survival, and intracranial progression-free survival. Exploratory objectives include analyzing association of treatment efficacy with minimal residual disease status, blood- and tissue-based genomic and transcriptomic signatures, tumor infiltrating immune cells, and peripheral blood NK cell and CD8+ T cell activity. Five of the planned 30 patients have been enrolled to date. Clinical trial information: NCT05903092 .

Trilaciclib use for prevention of hematological adverse events in chemotherapy: A meta-analysis of real-world studies and clinical trials.

e24130 Background: Trilaciclib, a cyclin-dependent kinase (CDK)-4 and -6 inhibitor, is the only FDA-approved agent that preemptively protects hematopoietic stem cells from chemotherapy-induced myelosuppression (CIM) without compromising efficacy. It transiently arrests hematopoietic stem cells in the G1 phase, thus temporarily blocking progression through the cell cycle and protecting progenitor cells from cytotoxicity. It has been approved for use in extensive-stage small-cell lung cancer (SCLC). Limited real-world evidence of its efficacy exists owing to its recent approval. We sought to enhance our understanding and evaluate the preventive effect of trilaciclib through a combined meta-analysis of clinical trials and retrospective studies. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus from inception until December 2023. Retrospective cohort studies and randomized-controlled trials with trilaciclib and non-trilaciclib arms were included. The primary outcomes of interest were CIM-related grade ≥3 hematological adverse events, and secondary outcomes included supportive care interventions to remedy CIM. Quantitative meta-analyses were conducted using the random-effects model on STATA v17. Results: The meta-analysis comprised seven studies, including four clinical trials and three real-world retrospective studies, including 6537 patients with extensive SCLC or locally recurrent or metastatic breast cancer. Chemotherapy regimens in SCLC patients included the combination of etoposide/platinum (E/P), E/P/PD-L1 inhibitors, or topotecan, and gemcitabine/carboplatin in patients with breast cancer. The mean age of the patients was 63.28 ± 5.31 years, and 49.21% were males. Administration of trilaciclib led to a reduction in the incidence of febrile neutropenia (2.41% vs. 7.56% OR = 0.35), severe neutropenia (21.76% vs. 41.91% OR = 0.57), anemia (18.02% vs. 32.41% OR = 0.51), and thrombocytopenia (20.06% vs. 31.25% OR = 0.62). Utilization of cytopenia-supportive therapies, including granulocyte colony-stimulating factor use (40.47% vs. 81.01% OR = 0.61) and RBC transfusions (16.66% vs. 18.25% OR = 0.59) were significantly lower in the trilaciclib cohort as compared to control. The overall response rate (mean difference = 1.09,95% CI = 0.74–1.60) and overall survival (OR = -0.02 95% CI = -0.95-0.92) were similar, and progression-free survival was noted to be longer in the trilaciclib group (mean difference = 1.75, 95% CI = 0.75-2.75). Conclusions: Trilaciclib use consistently demonstrated efficacy in reducing CIM, thus lowering cytopenia-related healthcare utilization without compromising treatment efficacy in trials and real-world settings. Its novel mechanism of action offers great promise, and further studies with larger sample sizes on various cancers will corroborate existing evidence.

Real world outcomes in extensive stage small cell lung cancer (ES-SCLC) treated with consolidative thoracic radiation (cTRT) and chemoimmunotherapy (CIT): A population level study.

Real world outcomes in extensive stage small cell lung cancer (ES-SCLC) treated with consolidative thoracic radiation (cTRT) and chemoimmunotherapy (CIT): A population level study.

The results of adding immunotherapy to chemotherapy in patients with small cell lung cancer: Registurk-Lung study—Real-world data.

e20006 Background: Evaluation of real-world data together with data in clinical studies is very important in the evaluation of treatment algorithms. In real life, treatments are applied to the elderly, patients with poor performance and unusual groups with comorbidities. Determining these treatment results is important in the creation of treatment algorithms. The studies on the addition of immunotherapeutic agents to the standard chemotherapy regimen in patients with small cell lung cancer have found a significant survival advantage. In this study, we evaluated the real-life reflections of the results of these clinical trials. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 1008 patients with extensive stage small cell lung cancer were evaluated between December 2021 and December 2023 in 42 centers representing the whole country. The demographic, histopathological, molecular and clinical data of the patients were recorded. The relationship between progression-free survival (PFS) time and overall survival (OS) time with these characteristics was investigated. Results: The median age was 64 (31-88) years and 17.6% of the patients were female. The proportion of patients who never smoked was only 4.7 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. At the time of diagnosis, brain metastases were present in 13.9 % of the patients and liver metastases were present in 12.1% of the patients. Only 19.4 percent of patients received chemoimmunotherapy. Eighty-three percent of the patients received atezolizumab as immunotherapy in combination with chemotherapy and as maintenance treatment. The other patients received durvalumab and pembrolizumab.Patients who did not receive immunotherapy received platinum plus etoposide chemotherapy regimen as a medyan 4 cycle. The overall response rate was 49.0 % in the chemotherapy group and 52.8 % in the combination group. The PFS was 7.6 (95% CI: 6.9-8.3) months in chemoimmunotherapy group and 7.3 (95% CI: 6.5-8.1) months in chemotherapy group. Also, the OS was 15.5 months (95% CI: 11.1-19.9) in chemoimmunotherapy group and 11.8 (95% CI: 10.5-13.2) months in chemotherapy group. When the two groups were compared, there was a positive trend in terms of PFS in the immunochemotherapy group, but this difference was not statistically significant (p:0,802). In terms of overall survival, there was a statistically significant improvement in the chemoimmunotherapy group (p:0,049). Conclusions: The addition of immunotherapy to the treatment of patients with small cell lung cancer, which we have been treating with dual combination chemotherapy for many years, has provided a survival benefit. This situation brings with it new hopes for future studies.

Cost trends in standard-of-care cancer treatments, 2017-2021.

11073 Background: Financial burden of cancer care in the United States is substantial. Prior studies have explored price trends at the level of individual cancer drugs but not that of clinical indications, which can be impacted not only by changes in drug prices but also changes in standard-of-care. This study evaluates temporal trends in the cost of providing the contemporary best guideline-concordant therapy for each cancer indication. Methods: We analyzed trends in the cost of the standard-of-care treatments for the 20 most prevalent cancer types, using NCCN Guidelines to identify the standard-of-care (SOC) treatment for each indication. Our primary comparison of interest was the cost of providing the SOC treatment regimen for each indication in 2021 vs. 2017. All solid tumor treatment indications present in the NCCN Guidelines at both study time points, 7/1/2017 and 7/1/2021, were included. Indications that involved radiotherapy or stem cell transplant among the treatment options were excluded. Costs of all recommended treatment options for each included indication were calculated using Medicare reimbursement rates. We included costs of the antineoplastic agents themselves as well as necessary supportive medications. Costs were inflation-adjusted to 2021 USD. We identified the SOC treatment for every indication at both time points by referring to NCCN Evidence Blocks and identifying the regimen(s) with the highest scores (prioritizing Efficacy, then Safety, then Quality, then Consistency, in that order). If multiple SOC treatments for a single indication had identical scores, we chose the least-costly treatment. Results: 83 clinical indications across 16 solid tumor cancer types (bladder, brain, breast, colon, kidney, liver, lung, melanoma, oropharyngeal, ovary, pancreas, prostate, rectal, soft tissue, stomach, and uterus) were included. Median SOC cost was $8,364 (IQR = $3,838, $15,783) in 2017, compared to a median of $4,290 (IQR = $1,438, $14,947) in 2021. 57 indications (68.7%) had lower SOC costs in 2021 vs 2017, with median change of -$935 (IQR = -$4,432, +$452), representing a 31% decrease (IQR = -50%, 8%). Gastric cancer perioperative chemotherapy had the biggest absolute cost decrease at $65,612 (-90%), while extensive stage small cell lung cancer had the biggest absolute increase at $37,213 (706%). 45 indications (54.2%) had the same SOC regimen across this study period, of which 75.6% saw price drops. Of the 38 indications with new SOCs, 60.5% had lower costs. Conclusions: Majority of the best SOC treatments decreased in cost over a 4 year period. Although introduction of newly approved drugs can cause large price increases for some indications, more commonly the financial cost of delivering the standard-of-care treatment for a given cancer trended down due to slower-than-inflation price increases and new generic entrants.

An open-label, multicenter, phase Ib/II study of the ATR inhibitor SC0245 in combination with irinotecan in patients with relapsed and refractory extensive stage small cell lung cancer (ES-SCLC).

8102 Background: Ataxia telangiectasia and Rad3 related (ATR) is activated in response to replication stress induced by topoisomerase 1 inhibitors (TOP1i) and other DNA damaging agents. SC0245 is a novel potent ATR inhibitor, showing synergistic inhibitory effects when combined with TOP1i in DMS-114 and H446 small cell lung cancer. This is the first report on an ongoing phase Ib/II study of SC0245 in combination with irinotecan (IRI) in patients (pts) with ES-SCLC (ClinicalTrials.gov: NCT05731518). Methods: Multiple escalating doses of SC0245 are being administered orally with a fixed dose of IRI. Pts are being enrolled into five escalating dose cohorts (80 mg once daily (QD), 120 mg QD, 80 mg twice daily (BID), 120 mg BID, 160 mg BID) using a BOIN design. SC0245 is administered daily for 3 days weekly x 3 (e.g, Days 1-3, 8-10 and 15-17) with IRI 80 mg/m2 on Days 1, 8 and 15. Cycles are repeated every 4 weeks. The primary endpoint is the rate of dose-limiting toxicity (DLT). Tumor assessments are being performed every 8 weeks using RECIST v1.1. Dose expansion in ES-SCLC patients will follow after definition of the recommended phase 2 dose (RP2D). Results: As of the data cut-off-date (December 21, 2023), 15 pts (median age, 65; male, 73.3%) with previously treated solid tumors have been enrolled, with 3, 4, 3 and 5 pts in 80mg QD, 120mg QD, 80mg BID and 120 mg BID dose cohorts, respectively. 12 of 15 pts were DLT evaluable, and one DLT event (Grade 3 febrile neutropenia) occurred in the 80 mg QD dose cohort. Cytopenia, diarrhea, and liver function test elevations, were the main adverse events (AEs) experienced in 73.3%, 46.7% and 40% pts, respectively. Most AEs were grade 1 or 2 in severity and manageable. The only ≥ Grade 3 TRAEs experienced by more than 2 subjects has been leukopenia (3/15, 20.0%). No drug-related deaths occurred. Among the 9 pts who were evaluable for tumor response, one confirmed partial response (PR) was reported in a pt with ES-SCLC (progressed on prior 1st line of etoposide + carboplatin + serplulimab treatment) treated in the 120mg QD dose cohort, and the response sustained for 32+ weeks; five pts (5/9, 55.6%) had stable disease (SD) as their best response. PK characteristics indicated that SC0245 was rapidly absorbed (median Tmax, 1.0 to 2.0 h), and drug exposure was proportional to dose for the QD and BID regimens. No drug-drug interactions (DDI) between SC0245 and either IRI or its active metabolite SN38 were observed. Conclusions: SC0245 exhibited favorable safety and PK characteristics when administered in combination with IRI at doses ranging from 80mg QD to 120mg BID and the regimen has demonstrated preliminary antitumor activity in ES-SCLC, supporting further evaluation of the regimen in ES-SCLC and other relevant malignancies. Clinical trial information: NCT05731518 .

First-line sintilimab combined with platinum-based chemotherapy in extensive stage small cell lung cancer: A phase II study and post-hoc biomarker analysis.

e20127 Background: Immune checkpoint inhibitors (ICIs) combined with etoposide and platinum-based chemotherapy improves prognosis of patients with extensive-stage small-cell lung cancer (ES-SCLC). However, nearly 40% of patients do not benefit from Immunochemotherapy. Herein, this phase II study of first-line immunochemotherapy was conducted aiming to investigate potential biomarkers associated with therapeutic efficacy. Methods: A multi-center, single-arm, prospective phase II trial (ChiCTR2000038354) was designed and conducted to evaluate the efficacy and safety of sintilimab combined with platinum-based chemotherapy in patients with ES-SCLC who had not previously received treatment. The primary endpoint of this study is progression-free survival (PFS), with patients being defined as disease progression according to RECIST 1.1. Pre-treatment FFPE samples were analyzed using whole exome sequencing (WES) and whole transcriptome sequencing (WTS) to investigate biomarkers. Results: A total of 44 patients were included in the study, with a median follow-up of 10 months and a median PFS of 7.57 months. 8 patients with a PFS greater than 6 months were defined as the responder group (R group) and 5 patients with a PFS less than 6 months belonged to the non-responder group (NR group). WES and WTS were performed on the pre-treatment samples of these 13 patients. WES results revealed mutation frequencies of TP53 (69%), RB1 (31%) and FAT1 (31%) aligning with prior research. Significantly, ZFHX4 mutations correlated with R group (p = 0.05). Genomic instability, as defined by Homologous Recombination Deficiency (HRD) scores, displayed higher scores in NR group than in R group (p = 0.023), which suggests potential benefits of PARP inhibition in the NR group. WTS data revealed that higher M2/M1 macrophage ratio (p = 0.028) in NR group. Additionally, the NR group demonstrated significant VEGFA overexpression. Besides, NOTCH-signaling (p = 0.034), KRAS-signaling-DN (p&lt;0.001), Angiogenesis (p&lt;0.001) and EMT (p&lt;0.001) pathway were also enriched in NR group. Conversely, M1 macrophages (p = 0.079), CD4+T cells (p = 0.093), Mast cells (p = 0.045), NK cells (p = 0.045) and neutrophils (p = 0.06) was higher in R group. Conclusions: This study highlights genomic instability as well as activation of cancer hallmarks such as angiogenesis, EMT may result the resistance to immunotherapy in ES-SCLC patients. These findings may shed light on combinational strategy overcoming therapeutic resistance. Clinical trial information: ChiCTR2000038354.

A real-world study of anlotinib in combination with PD-L1 inhibitors plus chemotherapy as first-line therapy for extensive-stage small cell lung cancer.

e20135 Background: Current first-line treatment options for extensive stage small cell lung cancer (ES-SCLC) are the PD-L1 inhibitor in combination with chemotherapy. Although these regimens have improved outcomes, most patients experience disease progression (PD), and median survival remains approximately 12 months. Anlotinib represents a tyrosine kinase inhibitor targeting multiple receptor tyrosine kinases, achieved good efficacy in third-line therapy in ES-SCLC. We conducted a real-world study to explore the safety and efficacy of adding anlotinib to the current first-line therapy in ES-SCLC. Methods: This real-world study included 16 patients with ES-SCLC treated with antirotinib in combination with the PD-L1 inhibitor and etoposide and cisplatin chemotherapy at our hospital between Oct 2020 and Nov 2023. Patients received six cycles of a standard dose of the PD-L1 inhibitor (Atezolizumab; Adebrelimab; Envafolimab; Nivolumab; Pembrolizumab; Tirelizumab or Sugemalimab) in combination with cisplatin (25 mg/m2, day 1-3 of each cycle) and etoposide (100 mg/m2, day 1-3 of each cycle), and anlotinib was taken orally (4-6mg, day 1-14 of each cycle). Maintenance PD-L1 inhibitor plus anlotinib was followed in a 21-day cycle until disease progression, intolerant toxicity, or longer than 2 years of treatment. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Secondary outcomes were disease control rate (DCR), objective response rate (ORR), and adverse reactions. Treatment response and adverse events (AEs) were assessed using the RECIST 1.1 and CTCAE 5.0, respectively. Results: A total of 16 patients were recruited. The median age was 72 years (66-76). Four patients (25%) had brain metastases at baseline, and seven patients (43.8%) had liver metastases. Median PFS was 10.8 months (95% CI, 8.3-13.3 months) and the median OS was 16.4 months (95% CI, 9.6-23.2 months). Totally 15 and 1 participants showed PR and SD, respectively. ORR and DCR were 93.8% and 100%. All patients had treatment-related AEs, of which grade 3-4 AE occurred in 50% (8/16). No serious infection or treatment-related death occurred. Myelosuppression was the most common AE, such as anemia (100%), leukocytopenia (100%), lymphocytopenia (100%), neutropenia (87.5%), and thrombocytopenia (50%). Other common AEs included hypoproteinemia (68.8%); hyponatremia (62.5%); creatinine elevation (56.3%), proteinuria (43.8%); hypertension (37.5%) and hypertriglyceridemia (37.5%). No unexpected AEs were found in this study. No patient stopped treatment due to intolerable toxicity. Conclusions: The addition of anlotinib to first-line immunotherapy in combination with chemotherapy results in extended PFS and OS in patients with ES-SCLC without additional AEs. The preliminary results warrant further investigation of this treatment modality in ES-SCLC.

A retrospective study of first line atezolizumab-carboplatin-etoposide in extensive-stage small cell lung cancer: Real world data from a Spanish tertiary center.

e20100 Background: The association of immune checkpoint inhibitors (ICIs) with Platinum-Etoposide (PE) has been established as the standard treatment in extensive stage Small Cell Lung Cancer (ES-SCLC). We present a real-world analysis, conducted in a Spanish tertiary hospital, that assesses the efficacy and safety of Atezolizumab combined to Carboplatin-Etoposide (Atezo-CE) in first-line ES-SCLC treatment, based on the Impower-133 Clinical Trial (CT). Methods: In this longitudinal, retrospective study, we analysed the patients (pts) diagnosed with ES-SCLC and treated at our center from July 2020 to June 2023, comparing outcomes of PE chemotherapy and Atezo-CE regime. Primary endpoints were overall survival (OS), progression-free survival (PFS) and safety. We contrasted our findings to those obtained in trials that used different ICIs: Impower-133 (Atezolizumab), CASPIAN (Durvalumab) or KEYNOTE-604 (Pembrolizumab). Data analysis employed Chi-square, Kaplan-Meier and Log-Rank. Results: Over 35 months (m), 41 pts with ES-SCLC were treated in our center: 19 pts received PE (57.9% Cisplatin and 42.1% Carboplatin), and 22 received Atezo-CE. In the PE group: 42.1% completed 6 cycles, 21.1% 4 cycles, and 36.8% less than 4. In the Atezo-CE cohort: 81.8% completed 4 cycles, and 18.2% less than 4. Regarding Performance Status (PS) in the PE cohort vs the Atezo-PE group: PS 0 0 vs 4.5%; PS 1 47.4 vs 77.3%; PS 2 42.1 vs 18.2%; PS 3 10.5 vs 0%. Corticosteroid therapy was ongoing in 52.6% vs 50% of PE vs Atezo-CE pts, respectively, adding the ICI in later cycles without affecting total cycles of Atezo received (6.8 in our study vs 7 in the Impower-133). Adverse effects (AEs) occurred in 73.7% of PE pts vs 100% of Atezo-CE pts (68.2% chemo-induced and 31.8% immune-related). Common AEs in both groups were anemia, thrombopenia, leukopenia, asthenia and vomiting. Skin and thyroid AEs were the most frequent ICI-related. Chemotherapy dose reduction occurred in 47.4% vs 27.3% and suspension in 5.3% vs 13.3% of PE pts vs Atezo-CE pts, respectively. OS was higher in the Atezo-CE group, 11.7m (95% CI: 9.2-14.2m) compared to 6.8m (95% CI: 3.8-9.8m) in the PE cohort, p-value 0.008. PFS also favoured Atezo-CE pts, 6.9m (95% CI: 5-8.7m) vs 5m (95% CI: 2.8-7.2m) in the PE cohort, though not statistically significant, p-value 0.249. Compared to the CTs Impower-133, CASPIAN and KEYNOTE-604, which reported OS of 12.3m, 12.9m and 10.8m, respectively, and PFS of 5.2m (Impower-133) and 4.2m (KEYNOTE-604), our study with pts with worse PS and needing corticosteroids at treatment initiation (exclusion criteria in CTs), showed comparable outcomes. Conclusions: Our study underscores the importance of adding ICIs to ES-SCLC first-line treatment. It further emphasizes the need for a deeper knowledge in molecular profiling and biomarker-driven strategies to tailor ES-SCLC therapy more effectively.