Small Cell Lung Cancer Patients Research Articles

First-line chemoimmunotherapy for patients with small-cell lung cancer and interstitial lung abnormality: CIP risk and prognostic analysis.

Patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy face a potential risk of developing checkpoint inhibitor-related pneumonitis (CIP). However, there is no clear understanding of the specific link between interstitial lung abnormality (ILA) and CIP in patients with small-cell lung cancer (SCLC). In addition, the prognosis of SCLC patients with ILA who receive chemoimmunotherapy is uncertain. Our study aimed to investigate the effect of ILA on the occurrence of CIP in SCLC patients receiving first-line chemoimmunotherapy and to assess its relationship with prognosis. We conducted a retrospective analysis of SCLC patients who received chemoimmunotherapy as a first-line treatment between January 2018 and April 2024. The diagnosis of ILA was assessed by two experienced pulmonologists based on pretreatment chest computed tomography images. We investigated independent risk factors for CIP using logistic regression analysis and factors affecting PFS and OS using Cox regression analysis. A total of 128 patients with SCLC were included in the study. ILA was present in 41 patients (32.03%), and CIP occurred in 16 patients (12.50%). In multivariate logistic regression analysis, previous ILA (OR, 5.419; 95% CI, 1.574-18.652; p = 0.007) and thoracic radiation therapy (TRT) (OR, 5.259; 95% CI, 1.506-18.365; p = 0.009) were independent risk factors for CIP. ILA (HR, 2.083; 95% CI, 1.179-3.681; p = 0.012) and LDH (HR, 1.002; 95% CI, 1.001-1.002; p < 0.001) were statistically significant for increased mortality risk in multivariate Cox regression analysis. In SCLC patients receiving first-line chemoimmunotherapy, baseline ILA is a risk factor for CIP and is associated with poorer prognosis.

Risk stratification model for foreseeing overall survival in Chinese patients with initially metastatic small-cell lung cancer.

The study was outlined to develop and approve a nomogram and chance stratification demonstrate for foreseeing overall survival of Chinese patients with at first metastatic small-cell lung cancer (SCLC). We collected information from the Surveillance, Epidemiology, and End Results (SEER) database approximately Chinese SCLC patients with at first distant metastases between 2010 and 2015. Patients with incomplete data about the follow-up time or clinicopathological information were excluded. The included patients were randomized into the training and validation set. Univariate and multivariate Cox proportional hazard regression models were performed. By integrating the significant variables screened, a prescient nomogram and risk stratification model were developed. In addition, we collected 198 small-cell lung cancer patients with metastasis at diagnosis from the case database of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine as an external validation cohort. In all, 421 patients were screened from the SEER database. Multivariate examination showed that age (P = .049), sex (P = .001), grade (P = .008), chemotherapy (P = .001), liver metastasis (P = .001), and pleural invasion (P = .012) were independent prognostic factors. The C-indicator of the nomogram to anticipate overall survival was higher than that of the eighth edition of the American Joint Committee on Cancer Tumor Node Metastasis classification system (0.75 vs 0.543; P < .001). A risk stratification model was encouraged to be created to precisely classify patients into 2 prognostic bunches. The survival rates anticipated by the nomogram appeared to have critical qualifications from the Kaplan-Meier curves in the entire SEER cohort. Calibration curves and survival predictions also showed strong accuracy and consistency in the external validation cohort. The nomogram provided a clear prognostic superiority over the traditional Tumor Node Metastasis system. It could help clinicians make individual risk predictions for initially metastatic Chinese SCLC cancer patients and give necessary treatment recommendations.

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

P1.09A.03 Concurrent Combination of EGFR-TKIs and Thoracic Radiation Therapy for Metastatic Non Small Cell Lung Cancer Patients

MA17.11 NOTCH1 Expression Is Associated with Overall Survival in Small Cell Lung Cancer Patients Treated with Atezolizumab in IMpower133

MA17.11 NOTCH1 Expression Is Associated with Overall Survival in Small Cell Lung Cancer Patients Treated with Atezolizumab in IMpower133

P3.13C.02 A Plasma Proteomics-Based Model for Clinical Benefit Prediction in Small Cell Lung Cancer Patients Receiving Immunotherapy

P3.13C.02 A Plasma Proteomics-Based Model for Clinical Benefit Prediction in Small Cell Lung Cancer Patients Receiving Immunotherapy

Combining serum CDK1 with tumor markers for the diagnosis of small cell lung cancer.

An investigation of the diagnostic and clinical value of cell cycle-dependent kinase 1 (CDK1) in small cell lung cancer (SCLC). A large tertiary hospital in Jiangxi Province enrolled 80 SCLC cases, 105 cases of non-small cell lung cancer (NSCLC), 114 cases of pulmonary nodule (PN) and 60 control cases from December 2022 to December 2023. ELISA was used to measure CDK1 levels in serum. The expression levers of neuron-specific enolase (NSE), Pro gastrin-releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCA), carcinoembryonic antigen (CEA), carbohydrate antigen 199 (CA199) and cytokeratin 19 fragment (YFRA21-1) were detected by electrochemiluminescence immunoassay. ①CDK1, ProGRP, NSE, and CA199 expressions were significantly higher in the SCLC group compared to the NSCLC, PN and Control groups (P < 0.01). ②Spearman correlation analysis showed that serum levels of CDK1, NSE, and ProGRP were associated with clinical staging and lymph node metastasis in SCLC patients (P < 0.05). ③The serum levels of CDK1, NSE, and ProGRP in patients with extensive-disease (ED) SCLC were higher than those in patients with limited-disease (LD) SCLC (P < 0.05), and the serum levels of CDK1, NSE, and ProGRP in SCLC patients with lymph node metastasis were higher than those without lymph node metastasis (P < 0.05). ④Compared with the NSCLC group, the AUC of subjects diagnosed with SCLC by CDK1 was the largest and the sensitivity was the highest, 0.831 and 72.50%, the specificity of ProGRP in diagnosing SCLC is the highest, at 95.20% (P < 0.01). Compared with the PN group, CDK1 had the highest AUC, sensitivity, and specificity in diagnosing SCLC, with values of 0.93%, 88.80%, and 94.70%, respectively (P < 0.01). ⑤The combination of CDK1, ProGRP and NSE had the highest AUC and sensitivity of 0.903 and 86.30% for the diagnosis of SCLC (P < 0.01). CDK1 not only plays an important role in assisting the diagnosis of SCLC but also in the differential diagnosis between SCLC and NSCLC. The combination of CDK1 and NSE and ProGRP can significantly improve the diagnostic performance and provide new ideas for the clinical diagnosis of SCLC.

Prophylactic cranial irradiation in patients with resected small-cell lung cancer: A systematic review and meta-analysis.

Prophylactic cranial irradiation (PCI) was recommended for limited-stage small-cell lung cancer (SCLC) patients with complete or partial response to primary chemoradiotherapy. But it is still controversial regarding its role in SCLC patients who have had radical resection. This meta-analysis aims to evaluate the efficacy of PCI in resected SCLC patients. We searched PubMed, EMBASE, Web of Science, CENTRAl, and ClinicalTrials for controlled trials and cohort studies regarding PCI in postoperative SCLC patients. The correlation between PCI and post-operative outcomes in SCLC patients, including survival and brain metastasis rate (BMR), was examined using hazard ratios (HRs) and risk ratios with corresponding 95% confidence intervals. Quality of studies was assessed by the Newcastle-Ottawa Scale (NOS), and publication bias was assessed by Begg's test. Meta-analysis of eight studies with 2688 patients in total showed PCI was associated with improved overall survival (OS) for resected SCLC (HR: 0.65, 95% CI: 0.57-0.75, p < 0.01). In addition, subgroup analysis on three studies including 923 patients confirmed the protective role of postoperative PCI in N0 SCLC patients (HR: 0.79, 95% CI: 0.61-0.97, p < 0.05). There was also a significant reduction in BMR in the PCI group pooled from six studies (HR: 0.58, 95% CI: 0.40-0.85, p < 0.01). The use of PCI delayed brain recurrence and improved OS in patients with resected, stage I-III SCLC. Importantly, patients with N0 SCLC can also benefit from postoperative PCI. In future studies, PCI's role in patients with resected N0 SCLC at different T stage may need to be explored.

Food Aversion, Systemic Inflammation and Intramuscular Adipose Tissue are Mortality Predictors in Advanced Lung Cancer Patients

ABSTRACTBackgroundCancer cachexia, systemic inflammation and muscle wasting are associated with poor survival in non–small cell lung cancer (NSCLC) patients (pts). We hypothesized whether neutrophil‐to‐lymphocyte ratio (NLR) and intramuscular adipose tissue/skeletal muscle index (IMAT/SMI) would predict prognosis in metastatic NSCLC (mNSCLC). In addition, we verified the role of a cancer cachexia questionnaire (EORTC‐QLQ‐CAX24) in the survival prediction.MethodsWe analysed a prospective cohort of 128 treatment‐naive mNSCLC pts (April 2017 to May 2020). We evaluated QoL using the EORTC‐QLQ‐C30 and EORTC‐QLQ‐CAX24 scales. We used the baseline NLR as a surrogate of systemic inflammation. We did evaluate IMAT/SMI using baseline plain computed tomography imaging. Cox multivariate regression, including age, sex, ECOG‐PS and histology as covariates, was performed.ResultsElevated NLR (hazard ratio [HR] 1.26, 95% confidence interval [CI]: 1.01–1.59, p = 0.038), IMAT/SMI ratio (HR 1.37, 95% CI: 1.03–1.84, p = 0.032) and high CAX24 scores for food aversion (HR 1.52, 95% CI: 1.13–2.03, p = 0.006) were associated with worse prognosis in mNSCLC. Indeed, higher ECOG‐PS (Spearman rho = 0.208, p = 0.027), CAX24 scores for food aversion (Spearman rho = 0.197, p = 0.036), loss of control (Spearman rho = 0.212, p = 0.024) and eating and weight loss worry domains (Spearman rho = 0.219, p = 0.020) were associated with elevated NLR levels.ConclusionsElevated NLR, IMAT/SMI ratio and CAX24 score for food aversion are independently associated with worse survival in mNSCLC. These data underscored the importance of cachexia features as negative prognostic factors in mNSCLC and revealed the EORTC‐QLQ‐CAX24 questionnaire as a new tool for helping clinical decision‐making.Trial Registration: ClinicalTrials.gov identifier: NCT03960034 and NCT04306094

Clofazimine inhibits small-cell lung cancer progression by modulating the kynurenine/aryl hydrocarbon receptor axis

Small cell lung cancer (SCLC) is one of the highly metastatic malignancies that contributes to ∼15 % of all lung cancers. Most SCLC patients (50–60 %) develop osteolytic bone metastases, significantly affecting their quality of life. Among several factors, environmental pollutant 2,3,7,8-Tetrachlorodibenzodioxin (TCDD) and kynurenine (Kyn), an endogenous ligand derived from tryptophan (Trp) metabolism, activate the aryl hydrocarbon receptor (AhR) and are responsible for SCLC progression and metastasis. Further, elevated AhR expression in bone cells intensifies bone resorption, making the Kyn/AhR axis a potential target for the bone metastatic propensity of SCLC. We first assessed the expression profile of AhR in human SCLC cell lines and found a significantly increased expression compared to normal lung cells. Additionally, we also evaluated the clinical significance of AhR expression in the patient samples of SCLC along with the relevance of the same in the Rb1fl/fl; Trp53fl/fl; MycLSL/LSL (RPM) mouse model using immunohistochemistry and found the higher AhR expression in the patient samples and RPM mouse tumor tissues. Using computational simulations, we found that clofazimine (CLF) binds at the activator (Kyn) binding site by forming a stable complex with AhR. The CLF binding with AhR was favored by Van der Waals and hydrophobic forces, and the proteins retained their secondary structure. Furthermore, we found that Kyn treatment potentiates the migration and clonogenic ability of SCLC cell lines by activating Erk/Akt oncogenic signaling. Treatment with CLF reduces AhR expression, which inhibits Kyn-mediated proliferation of SCLC cells, induces apoptosis, and cell cycle arrest in the G2/M phase. Further, our examination indicates that Kyn treatment also promotes osteoblast-mediated osteoclast differentiation through RANKL. The treatment with CLF impedes RANKL expression and osteoclastogenesis, suggesting that CLF has the potential to be used as the therapeutic for SCLC patients having bone metastasis.

EP.13E.04 Racial Disparities in Genomic Subtypes of Small Cell Lung Cancer Patients

EP.13E.04 Racial Disparities in Genomic Subtypes of Small Cell Lung Cancer Patients

P1.13B.02 Radiation Necrosis in Small Cell Lung Cancer Patients

P1.13B.02 Radiation Necrosis in Small Cell Lung Cancer Patients

EP.11A.29 C-Reactive Protein's Impact on Immune Adverse Events in Non Small Cell Lung Cancer Patients Undergoing Immunotherapy: Meta-Analysis

EP.11A.29 C-Reactive Protein's Impact on Immune Adverse Events in Non Small Cell Lung Cancer Patients Undergoing Immunotherapy: Meta-Analysis

Bi-weekly irinotecan is an effective and convenient regimen in the treatment of relapsed or refractory small cell lung cancer

BackgroundDespite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients.MethodsThe study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment.ResultsOne hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction.ConclusionsIrinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration.

Chirurgie du cancer à petites cellules

Curative surgery for Small-Cell Lung Cancer (SCLCs) is rare, accounting for less than 5 % of surgeries for bronchopulmonary cancer. The rapid progression of SCLCs and their discovery at a metastatic or locally advanced stage generally exclude them from surgical strategy. Even in localized tumor forms, this surgery is rarely proposed. However, scientific societies (ASCO, ESMO, INCA) have established multimodal management recommendations including radical surgery for selected patients, despite very low levels of evidence. This primarily concerns stage I and sometimes stage II patients, if adjuvant chemotherapy is feasible. Including surgery, the median survival for stage I patients ranges from 28 to 54 months, and 5-year survival rates from 34 % to 65 %, values significantly higher than for non-operated patients. This surgery is not suitable for multi-site or “bulky” N2, but some N2 patients appear to benefit with 5-year survival rates exceeding 20 %. Salvage surgery after tumor re-evolution is possible under certain conditions. Lobectomy with lymph node dissection is the preferred intervention in this context, and the role of sub-lobar resection remains controversial. All these results justify medical combined to surgical discussions in Thoracic Oncology multidisciplinary tumor board for these SCLC patients. Thanks to screening programs and improved staging assessments, the more frequent diagnosis of less extensive forms will certainly highlight the role of surgery for SCLCs. 1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

MiR-4448/Girdin/Akt/AMPK axis inhibits EZH2-mediated EMT and tumorigenesis in small-cell lung cancer.

Small-cell lung cancer (SCLC) shows high enhancer of zeste homolog 2 (EZH2) expressions. EZH2-mediated epigenetics promote epithelial-mesenchymal transition (EMT), enhancing invasive and metastatic potential in malignancies. MicroRNAs (miRNAs), small noncoding RNAs, modulate EMT, determining tumor phenotypes. However, the association between miRNAs and EZH2 in SCLC remains to be clarified-we aimed to identify a novel tumorigenic mechanism through miRNAs, EZH2, and EMT in SCLC, leading to future therapeutic applications. We analyzed EZH2 and E-cadherin expressions in lung cancer cell lines and tumor tissues from 34 SCLC patients and confirmed EZH2 siRNA-mediated EMT inhibition. miRNA expression profiles were compared between EZH2 knockdown SCLC cells and negative control SCLC cells using miRNA array. We identified a target miRNA of EZH2 showing expressional differences in EZH2-knockdown cells and analyzed the impact of the miRNA on EZH2-mediated EMT and tumorigenesis. All SCLC cells showed increased EZH2 and decreased E-cadherin expressions. SCLC tissues had higher EZH2 and lower E-cadherin expressions than other lung cancer tissues. miRNA array revealed that miR-4448 expression increased in EZH2-knockdown SCLC cells. miR-4448 overexpression reduced tumor cell growth and prevented EMT. miR-4448 bound to the 3'UTR of the girdin gene and suppressed its expression, thereby decreasing Akt phosphorylation at Ser473. Attenuated Akt phosphorylation resulted in AMP-activated protein kinase (AMPK) phosphorylation at Thr172 and 183, enhancing EZH2 phosphorylation at Thr311. SCLC characterized high EZH2 expression and promoted EMT, compared with non-small cell lung cancer. miR-4448 inhibited Girdin expression, reducing Akt phosphorylation, and enhancing AMPK and EZH2 phosphorylation. Eventually, miR-4448 prevented EZH2-mediated EMT and tumorigenesis by modulating the Girdin/Akt/AMPK axis in SCLC. miR-4448 might be a potential SCLC inhibitor.

A simulated trial with reinforcement learning for the efficacy of Irinotecan and Ifosfamide versus Topotecan in relapsed, extensive stage small cell lung cancer

ObjectivesSynthetic data may proxy clinical data. At the absence of direct clinical data, this study aimed to compare Irinotecan and Ifosfamide (II) with Topotecan in synthetic, recurrent small cell lung cancer (SCLC) patients within a simulated clinical trial.Materials and methodsTwo simulation stages were conducted. Initially, 200 recurrent SCLC cases were simulated to replicate a previous phase 3 trial, testing the utility of Cox proportional hazards model and simulation methodology together, where patients were randomized to receive Cyclophosphamide, Adriamycin, Vincristine (CAV) or Topotecan. In the second stage, 600 recurrent SCLC patients were simulated and randomized to compare Topotecan versus II in terms of overall survival (OAS), using Reinforcement Learning (RL) and Cox proportional hazards model.ResultsCAV versus Topotecan comparison showed no statistical difference in overall survival (hazard ratio (HR): 0.89, 95% CI: 0.67–1.18, P = 0.418), aligning with the original clinical trial. For the Topotecan versus II comparison, the RL framework significantly favored the II arm (mean reward points: 193.43 versus − 251.82, permutation P < 0.0001). Likewise, II arm exhibited superior median OAS compared to Topotecan arm (11.12 versus 6.30 months). HR was 0.44 (95% CI: 0.38–0.52) with P < 0.0001, in favor of II.ConclusionArtificial trial results for CAV versus Topotecan matched the original trial, confirming indifference of OAS. Additionally, II yielded superior overall survival compared to Topotecan in recurrent SCLC patients. These demonstrate the potential of RL and simulation in conjunction with Cox modelling for similar studies. However, definitive conclusions necessitate a randomized clinical trial between II and Topotecan in this patient cohort.

Serum tumor markers and outcomes in lung cancer patients with brain metastases: a retrospective longitudinal cohort study.

Serum tumor markers (STMs) are recommended for cancer diagnosis and surveillance. However, their role in lung cancer with brain metastases (BM) is not yet clear. We aim to analyze the roles of baseline levels of STMs or ongoing STM surveillance on survival. This retrospective longitudinal cohort study included 1,169 lung cancer patients with BM. The STM data during disease course were collected. Distinct trajectory groups were identified using the latent class growth mixed model (LCGMM). The roles of STMs on survival were further analyzed using Kaplan-Meier analysis and Cox proportional hazard models. Serum levels of cytokeratin-19 fragment (CYFRA21-1) (P<0.001), carcinoembryonic antigen (CEA) (P=0.005) and neuron-specific enolase (NSE) (P<0.001) at baseline exhibited significant correlation with overall survival (OS) of patients with BM, serving as independent prognostic factors. Further analysis indicated that baseline CYFRA21-1, CEA, NSE as well as status of key driver genes were independent prognostic factors in non-small cell lung cancer (NSCLC) patients with BM, while for small cell lung cancer (SCLC) patients with BM, baseline NSE and receiving chemotherapy show independent correlations with survival. Furthermore, we delineated the dynamic trajectories of STMs based on changes in disease course. More specifically, compared to those showing a baseline-high trend in CEA levels, the survival of patients with either persistently-rising or consistently normal levels seemed to be more promising. For CYFRA21-1, both early-rising and later-rising trends were observed, indicating a prognosis inferior to that of individuals with normal-level trajectory. Likewise, for NSE, patients with persistently-rising or persistently-descending trends showed no significantly survival difference. However, in comparison with the status of driver genes, receiving radiotherapy and targeted therapy, the dynamic changes in STM levels lacked independent prognostic significance. Further analysis indicated that among BM patients lacking key driver genes, NSE trajectory (P<0.05), CYFRA21-1 trajectory (P<0.05) and receiving chemotherapy (P<0.001) were independent prognostic factors. Baseline levels of serum CYFRA21-1, CEA and NSE, as well as status of key driver genes are recommended for evaluating BM patients' outcome. Dynamic changes of STMs during disease course were not significantly associated with the final outcome of BM patients.

BUB1 Inhibition Overcomes Radio- and Chemoradiation Resistance in Lung Cancer.

Background: Despite advances in targeted therapies and immunotherapies, traditional treatments like microtubule stabilizers (paclitaxel, docetaxel), DNA-intercalating platinum drugs (cisplatin), and radiation therapy remain essential for managing locally advanced and metastatic lung cancer. Identifying novel molecular targets could enhance the efficacy of these treatments. Hypothesis: We hypothesize that BUB1 (Ser/Thr kinase) is overexpressed in lung cancers and its inhibition will sensitize lung cancers to chemoradiation. Methods: BUB1 inhibitor (BAY1816032) was combined with cisplatin, paclitaxel, a PARP inhibitor olaparib, and radiation in cell proliferation and radiation-sensitization assays. Biochemical and molecular assays evaluated the impact on DNA damage signaling and cell death. Results: Immunostaining of lung tumor microarrays (TMAs) confirmed higher BUB1 expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) compared to normal tissues. In NSCLC, BUB1 overexpression correlated directly with the expression of TP53 mutations and poorer overall survival in NSCLC and SCLC patients. BAY1816032 synergistically sensitized lung cancer cell lines to paclitaxel and olaparib and enhanced cell killing by radiation in both NSCLC and SCLC. Molecular analysis indicated a shift towards pro-apoptotic and anti-proliferative states, evidenced by altered BAX, BCL2, PCNA, and Caspases-9 and -3 expressions. Conclusions: Elevated BUB1 expression is associated with poorer survival in lung cancer. Inhibiting BUB1 sensitizes NSCLC and SCLC to chemotherapies (cisplatin, paclitaxel), targeted therapy (olaparib), and radiation. Furthermore, we present the novel finding that BUB1 inhibition sensitized both NSCLC and SCLC to radiotherapy and chemoradiation. Our results demonstrate BUB1 inhibition as a promising strategy to sensitize lung cancers to radiation and chemoradiation therapies.

Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients.

The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.

Surufatinib plus toripalimab combined with etoposide and cisplatin as first-line treatment in advanced small-cell lung cancer patients: a phase Ib/II trial

There is still room for improvement in first-line treatment of advanced small cell lung cancer (SCLC). This trial firstly investigated efficacy and safety of antiangiogenic therapy (surufatinib) (200 mg, qd, po) plus anti-PD-1 treatment (toripalimab) (240 mg, d1, ivdrip) combined with etoposide (100 mg/m², d1-d3, iv, drip) and cisplatin (25 mg/m², d1-d3, ivdrip) for advanced SCLC as first-line treatment, which has been registered on ClinicalTrials.gov under the identifier NCT04996771. The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab. The primary endpoint was progression-free survival (PFS). The secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. All of the 38 patients were enrolled for safety analysis, while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment. After a median follow-up of 21.3 months, the ORR was 97.1% (34/35), and the DCR and the tumor shrinkage rate were both 100% (35/35). The median PFS was 6.9 months (95% CI: 4.6 m–9.2 m) and the median OS was 21.1 months (95% CI: 12.1 m–30.1 m). The 12-month, 18-month, and 24-month OS rates were 66.94%, 51.39% and 38.54%. The occurrence rate of grade ≥3 treatment-emergent adverse events (TEAEs) was 63.2% (24/38), including neutrophil count decreased (31.6%, 12/38), white blood cell count decreased (23.7%, 9/38) and platelet count decreased (10.5%, 4/38). No unexpected adverse events occurred. This novel four-drug regimen (surufatinib, toripalimab, etoposide plus cisplatin) revealed impressive therapeutic efficacy and tolerable toxicities.