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SCLC

(Small Cell Lung Cancer)

Relevant Articles About Non Small Cell Lung Cancer Research and Clinical Trials

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SCLC (Small Cell Lung Cancer)DurvalumabOther: PlaceboTremelimumabActiveNot RecruitingArgentinaBelgiumCanadaChinaCzechiaGermanyIndiaItalyJapanKorea, Republic ofNetherlandsPolandRussian FederationSpainTaiwanTurkeyUnited KingdomUnited StatesVietnam 9NCT03703297Phase 3ADRIATIC
Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy

Study of Durvalumab + Tremelimumab, Durvalumab, and Placebo in Limited Stage Small-Cell Lung Cancer in Patients Who Have Not Progressed Following Concurrent Chemoradiation Therapy

NSCLC (Non-Small Cell Lung Cancer)Other CancersSCLC (Small Cell Lung Cancer)(vic-)trastuzumab duocarmazineRecruitingUnited States 0NCT02146170
Tissue Procurement and Natural History Study of People With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors

Tissue Procurement and Natural History Study of People With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors

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Effective PT in Largest IM Patient Series

KEY TAKEAWAYS The study aimed to report outcomes from a substantial series of IM treated with curative-intent proton therapy. The study's findings concluded proton therapy effectively treated IM with acceptable toxicity, representing a substantial patient cohort....

Jun 28, 2024

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Paclitaxel vs Pemetrexed Chemoimmunotherapy: SMARCA4 Deficiency

KEY TAKEAWAYS

  • The study aimed to analyze molecular profiles and optimal treatment for SMARCA4-deficient thoracic tumors.
  • The results revealed that chemoimmunotherapy with paclitaxel was effective for treating SMARCA4-deficient thoracic tumors.

SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) are identified as distinct entities in the 2021 WHO Classification of Thoracic Tumors. These tumors share demographic and molecular features with SMARCA4-deficient non-small cell lung cancer (NSCLC) (SMARCA4-dNSCLC), highlighting the need for further understanding through immunohistochemistry.

Mengting Shi and team aimed to characterize the molecular profiles of SMARCA4-deficient thoracic tumors (SDTT) and explore potential treatment strategies tailored to these tumors.

They studied a large group of patients from June 15, 2018, to November 15, 2023, including 196 SMARCA4-deficient and 438 SMARCA4-intact thoracic tumor patients. Patients were confirmed using immunohistochemistry. Clinicopathologic and molecular features were analyzed and compared. An additional cohort (n=34) was pooled to compare outcomes of first-line therapy efficacy.

The results showed that SDTT predominantly affects males with a smoking history, high tumor burden, and adrenal metastases. Most SMARCA4-deficient patients have Class-I truncating mutations, whereas class-II alterations and wild-type also exist. SDTT has a higher tumor mutation burden (TMB) and shorter median OS (16.8 months vs. not reached; P< 0.001) than SMARCA4-intact tumors.

SMARCA4 protein deficiency, not genetic mutations, drives these differences. SDTT resists chemotherapy but responds well to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P< 0.001), with paclitaxel-based chemoimmunotherapy offering longer PFS than pemetrexed-based ones (10.0 vs. 7.3 months, P= 0.028).

The study concluded that SMARCA4 protein deficiency drives higher TMB and poor prognosis. Chemoimmunotherapy is the best treatment, with paclitaxel-based regimens outperforming pemetrexed-based ones.

No funding information was provided.

Source: https://www.lungcancerjournal.info/article/S0169-5002(24)00352-0/abstract

Shi M, Pang L, Zhou H, et al. (2024). “Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.” https://doi.org/10.1016/j.lungcan.2024.107818

RANKL as Prognostic Marker in High PDL1 NSCLC

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic significance of soluble RANKL in patients with advanced NSCLC treated with PD1/PDL1 checkpoint inhibitors.
  • Researchers noticed that RANKL levels predict outcomes, with high PDL1 expression.

Receptor activator of nuclear factor kappa-B ligand (RANKL) can directly promote tumor growth and indirectly support tumor immune evasion by altering the tumor microenvironment (TME) and immune cell responses.

Michele Iuliani and the team aimed to assess the prognostic significance of soluble RANKL in patients with advanced non-small cell lung cancer (NSCLC) receiving programmed cell death 1 (PD1)/programmed death-ligand 1 (PDL1) checkpoint inhibitor therapy.

Researchers performed an inclusive analysis by measuring plasma RANKL levels in 100 patients with advanced NSCLC undergoing monotherapy with PD1/PDL1 checkpoint inhibitors. The optimal cut-off value was established using the Cutoff Finder package in R. Survival curves for four distinct patient groups based on their RANKL and PDL1 levels (high or low) were generated using the Kaplan-Meier method and compared with the log-rank test. The Cox regression model calculated HRs and 95% CIs for overall survival (OS) and progression-free survival (PFS).

Researchers found that the optimal RANKL cut-off was established at 280.4 pg/mL, dividing patients into high and low RANKL groups. A significant association was noted between elevated RANKL levels and decreased 24-month survival rates specifically in the high PDL1 expression subgroup (P=0.002). Furthermore, low RANKL levels combined with high PDL1 expression were associated with improved PFS (median 22 months, 95% CI 6.70 to 50 vs median 4 months, 95% CI 3.0 to 7.30, P=0.009) and OS (median 26 months, 95% CI 20 to not reached vs median 7 months, 95% CI 6 to 13, P=0.003), highlighting RANKL’s potential as an adverse prognostic indicator in these patients. Multivariate analysis confirmed RANKL as an independent negative prognostic factor for both PFS and OS, irrespective of other clinicopathological variables.

The study concluded that RANKL demonstrates significant prognostic and predictive value in patients with high PDL1 expression, emphasizing its role as a potential biomarker in advanced NSCLC treated with PD1/PDL1 checkpoint inhibitors.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/38908859/

Iuliani M, Simonetti S, Cristofani L, et al. (2024). “Circulating receptor activator of nuclear factor kappa-B ligand (RANKL) levels predict response to immune checkpoint inhibitors in advanced non-small cell lung cancer (NSCLC).” J Immunother Cancer. 2024 Jun 21;12(6):e009432. doi: 10.1136/jitc-2024-009432. PMID: 38908859.

IVIM and DKI Histogram Analysis for Predicting NSCLC

KEY TAKEAWAYS

  • The study aimed to assess IVIM and DKI histogram analysis with different ROI methods for predicting chemoimmunotherapy response in pts with NSCLC.
  • Researchers found whole tumor volume ROI more effective than single slice ROI for predicting chemoimmunotherapy response.

There is an urgent need to find a reliable and effective imaging method to evaluate the therapeutic efficacy of immunochemotherapy in patients (pts) with advanced non-small cell lung cancer (NSCLC).

Yu Zheng and the team aimed to investigate the capability of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) histogram analysis based on different region of interest (ROI) selection methods for predicting treatment response to chemoimmunotherapy in advanced NSCLC.

They performed an inclusive analysis involving 72 stage III or IV pts with NSCLC who received chemoimmunotherapy. IVIM and DKI imaging were conducted before treatment. Based on the Response Evaluation Criteria in Solid Tumors 1.1, pts were categorized into responders and non-responders groups. Histogram parameters of ADC, Dslow, Dfast, f, Dk, and K were measured using whole tumor volume ROI and single slice ROI analysis methods.

Variables with statistical differences were included in stepwise logistic regression analysis to identify independent parameters, which were then used to establish a combined model. The receiver operating characteristic curve (ROC) was employed to evaluate the predictive performance of the histogram parameters and the combined model.

About ADC, Dslow, and Dk histogram metrics were significantly lower in the responders group than in the non-responders group, while the histogram parameters of f were significantly higher in the responders group than in the non-responders group (all P < 0.05). The mean value of each parameter was better than or equivalent to other histogram metrics, where the mean value of f obtained from whole tumor and single slice both had the highest AUC (AUC = 0.886 and 0.812, respectively) compared to other single parameters. The combined model improved the diagnostic efficiency with an AUC of 0.968 (whole tumor) and 0.893 (single slice), respectively.

The study concluded that whole tumor volume ROI exhibited superior diagnostic capability over single slice ROI analysis. This suggests that whole tumor histogram analysis of IVIM and DKI has greater potential as a predictive tool for therapeutic response to chemoimmunotherapy in advanced NSCLC at the initial state.

This study was funded by the National Natural Science Foundation of China and by the Science and Technology Project of Gansu.

Source: https://pubmed.ncbi.nlm.nih.gov/38863062/

Zheng Y, Zhou L, Huang W, et al. (2024). “Histogram analysis of multiple diffusion models for predicting advanced non-small cell lung cancer response to chemoimmunotherapy.” Cancer Imaging. 2024 Jun 11;24(1):71. doi: 10.1186/s40644-024-00713-8. PMID: 38863062; PMCID: PMC11167789.

Diagnostic Biomarkers of EGFR Mutation in NSCLC Pleural Effusion

Diagnostic Biomarkers of EGFR Mutation in NSCLC Pleural Effusion

KEY TAKEAWAYS

  • TThe study aimed to investigate the metabolomic profile of MPE to identify biomarkers for EGFR mutations in patients with NSCLC.
  • Researchers noticed significant amino acid alterations in MPE aiding accurate diagnosis; further investigation is ongoing.

Malignant pleural effusion (MPE) is a common complication of non-small cell lung cancer (NSCLC). Patients with NSCLC exhibit a high rate of epidermal growth factor receptor (EGFR) mutations. The detection of EGFR mutations is usually time-consuming and costly.

Jiangqing Yu and the team aimed to identify the potential biomarkers of EGFR mutations in MPE of patients with NSCLC by metabolomics.

They performed an inclusive analysis, analyzing 58 MPE samples from 30 EGFR mutant and 28 wild-type patients with NSCLC using hydrogen nuclear magnetic resonance (1H NMR)-based metabolomics and UPLC-MS/MS-based amino acid analysis.

The 1H NMR study revealed a significant increase in lysine levels and a notable decrease in alanine levels in MPE of patients with NSCLC and EGFR mutation. Twelve amino acids in MPE were further analyzed by UPLC-MS/MS, showing significantly decreased alanine levels (6.34 ± 1.88 vs. 8.73 ± 3.68) and increased levels of leucine (3.13 ± 0.57 vs. 2.22 ± 0.13), lysine (2.19 ± 0.50 vs. 1.53 ± 0.40), and tyrosine (2.69 ± 0.71 vs. 1.89 ± 0.46) in EGFR mutation-positive patients.

Moreover, leucine (2.19 ± 0.50 vs. 1.53 ± 0.40), methionine (2.19 ± 0.50 vs. 1.53 ± 0.40), and threonine (2.19 ± 0.50 vs. 1.53 ± 0.40) levels were significantly lower in EGFR exon 19 mutation compared to exon 21 mutation patients. The logistic model achieved area under the receiver operating characteristic curves of 0.851 and 0.931 for classifying EGFR-mutant patients from wild-type controls and distinguishing between exon 19 and exon 21 mutations, respectively.

The study concluded that amino acid profiles in MPE are significantly altered and aid in accurately diagnosing EGFR-mutant patients from wild-type controls and distinguishing between exon 19 and exon 21 mutations. Further investigation into these biomarkers is warranted.

No funding information was provided.

Source: https://pubmed.ncbi.nlm.nih.gov/38868885/

Yu J, Xu H, Feng T, et al. (2024). “Identification of Potential Biomarkers of EGFR Mutation in Pleural Effusion of Non-Small Cell Lung Cancer Patients Based on Metabolomics.” Clin Lab. 2024 Jun 1;70(6). doi: 10.7754/Clin.Lab.2023.231105. PMID: 38868885.

ALI Enables Individualized Treatment In Operable NSCLC

KEY TAKEAWAYS

  • The study aimed to assess the potential of ALI in pts with NSCLC prognosis by constructing a nomogram model.
  • ALI and the nomogram model serve as reliable prognostic indicators and assist in individualized treatment for NSCLC.

Shixin Ma and the team determined the significance of the advanced lung cancer inflammation index (ALI) in patients (pts) with operable non-small-cell lung carcinoma (NSCLC). They constructed the nomogram model that offered valuable guidance for clinical practice.

Researchers selected a total of 899 pts diagnosed with NSCLC who underwent surgery at our hospital from January 2017 to June 2021 and evaluated the prognostic significance of the ALI, which was calculated using the formula body mass index (BMI) × serum albumin/neutrophil to lymphocyte ratio (NLR).

The receiver operating characteristic (ROC) curve was employed to obtain the optimal cutoff value of ALI while the Kaplan-Meier method was utilized for conducting survival analysis. OS was obtained by using a single-factor and stepwise regression multifactor analysis, employing the Cox proportional hazards model.

Results of multi-factor Cox proportional hazards regression analysis formed a firm basis to construct a nomogram model utilizing the R survival package. Internal validation of the nomogram model was conducted using the bootstrap method with 1,000 iterations. The prediction performance of the nomogram model was assessed using the concordance index (C-index), and its calibration was visually represented using calibration plots. The clinical utility of the nomogram model was further evaluated through decision curve analysis (DCA).

The optimal cut-off value of ALI was 70.06 while pts in the low ALI group (ALI < 70.06) exhibited significantly poorer survival outcomes. In multivariate analyses, tumor location, pathological stage, neuroaggression, and ALI-like factors were found to be independent predictors of operable NSCLC-specific survival.

From the above findings, the nomogram model was developed which demonstrated strong predictive accuracy, with a C-index of 0.928 (95% CI: 0.904-0.952) for OS and was internally validated by using the bootstrap method (B = 1000).

Excellent agreement between predicted and observed survival rates at 1-year, 2-year, and 3-year intervals was seen. ROC curves further highlighted the model’s predictive power, having area under the curve (AUC) values of 0.952 (95% CI: 0.925-0.979), 0.951 (95% CI: 0.916-0.985), and 0.939 (95% CI: 0.913-0.965) for 1-year, 2-year, and 3-year survival, respectively. DCA confirmed the clinical relevance and utility of the model in clinical relevance.

The study concluded that ALI serves as a reliable prognostic indicator in assessing pts with operable NSCLC, and its integration into a nomogram model enhanced the precision of personalized treatment and prognosis evaluation.

The study received no funds.

Source: https://pubmed.ncbi.nlm.nih.gov/38877553/

Ma S., Li Z. and Wang L. (2024). “The advanced lung cancer inflammation index (ALI) predicted the postoperative survival rate of patients with non-small cell lung cancer and the construction of a nomogram model.” World J Surg Oncol. 2024 Jun 14;22(1):158. doi: 10.1186/s12957-024-03432-3. PMID: 38877553; PMCID: PMC11177447.

cfDNA & DII as Early Prognostic Biomarkers in NSCLC

KEY TAKEAWAYS

  • The study aimed to evaluate the potential of DII as a diagnostic and prognostic biomarker in pts with NSCLC.
  • The cfDNA and DII represent a promising early prognostic tool.

Analysis of free DNA molecules shed from tumour cells in the plasma of patients (pts), referred to as circulating tumour DNA (ctDNA), in contrast to physiological circulating cell-free DNA (cfDNA), is nowadays exploited as liquid biopsy, a new emerging promising biomarker for diagnosis which assists in selection of proper treatment, and prognosis of cancer.

DNA integrity index (DII) is assessed by calculating the ratio between the concentration of long cfDNA strands released from tumour cells (ALU247) and the short strands released from normal cells (ALU115).

Nada Ezzeldin and the team determined to assess the DII, evaluated by the ratio of long to short cfDNA strands, as a potential diagnostic and prognostic biomarker for non-small cell lung cancer (NSCLC).

Researchers selected 48 NSCLC pts diagnosed with primary NSCLC before treatment initiation. About 30 COPD pts diagnosed clinically and radiologically, and subjected to chest high-resolution computerized tomography (CT), along with 40 healthy controls, were included. The cfDNA concentration and DII were measured using quantitative real-time polymerase chain reaction (qPCR).

The ALU115, ALU247, and DII levels were found to be significantly higher in NSCLC pts compared to both COPD pts (P< 0.0001) and healthy controls (P< 0.0001), and also higher in COPD pts compared to controls (P< 0.0001).

Furthermore, DII showed positive correlations with the stage of the tumour (P= 0.01), presence of tumour metastasis (P= 0.004), and adenocarcinoma histopathological subtype compared to other types (P= 0.02).

In evaluating the clinical utility of DII in NSCLC, ROC curve analysis revealed an area under the curve (AUC) of 0.91 at a cut-off value of 0.44, demonstrating overall accuracy of 85.6%, sensitivity of 90%, specificity of 83%, positive predictive value (PPV) of 78.1%, and negative predictive value (NPV) of 92.1%.

The study concluded that cfDNA and DII offer a promising noninvasive tool for the diagnosis and prognosis of NSCLC, demonstrating potential in screening, early detection, and disease monitoring.

The study was funded by the National Research Centre (NRC), Cairo, Egypt.

Source: https://pubmed.ncbi.nlm.nih.gov/38880832/

Ezzeldin N., El-Lebedy D., Hassan M., et al. (2024). “Evaluating circulating cell-free DNA and DNA integrity index as biomarkers in non-small cell lung cancer.” J Egypt Natl Canc Inst. 2024 Jun 17;36(1):21. doi: 10.1186/s43046-024-00219-1. PMID: 38880832.

Lorlatinib Shows Promise in TKI-Naive Advanced ROS1+ NSCLC

KEY TAKEAWAYS

  • The phase 2 trial aimed to investigate the antitumor activity and safety of lorlatinib in TKI naïve in patients with advanced ROS1-positive NSCLC.
  • The primary endpoint was to determine ORR.
  • Researchers noticed lorlatinib’s effectiveness and safety, supporting earlier treatment for ROS1-positive NSCLC.

ROS1 rearrangement is rare but an attractive therapeutic target in advanced non-small cell lung cancer (NSCLC). Currently, crizotinib, entrectinib, and reprotrectinib have been approved for ROS1-positive NSCLC. Lorlatinib is a potent, brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) that targets ROS1 as well as ALK.

Beung Chul AHN and the team aimed to investigate the antitumor activity and safety of lorlatinib in TKI naïve, advanced ROS1-positive NSCLC.

They conducted a prospective multi-center, single-arm, phase II study that enrolled TKI-naïve patients diagnosed with histologically or cytologically confirmed advanced ROS1-positive NSCLC, presenting with an Eastern Cooperative Oncology Group performance status of 2 or less and having received one or no prior platinum-based chemotherapy. Lorlatinib 100mg once daily was administered orally in continuous 21-day cycles until disease progression, unacceptable toxicity, consent withdrawal, or death.

The primary endpoint assessed was the objective response rate (ORR), with secondary endpoints including progression-free survival (PFS), overall survival (OS), and safety. Sample size calculation employed a 2-stage design to evaluate the null hypothesis (40%) and the alternative hypothesis (60%), with type I error (α) level of 10% and type II error (β) of 0.20.

About 32 patients with ROS1-positive NSCLC were enrolled between June 03, 2019, and April 26, 2023. The median age was 60, with 63% females, and all (100%) had adenocarcinoma histology. Among them, 21 (66%) were treatment-naive, and 11 (34%) had previously received platinum-based chemotherapy. The median duration of follow-up for response was 15.6 months (Interquartile Range [IQR], 10.3–30.4). Objective responses were observed in 22 patients (69%; 95% confidence interval [CI], 52 to 83). Median PFS was 35.8 months (95% CI, Not Reached [NR] to NR), and OS was NR.

Among treatment-naive vs. previously treated patients, the objective response rates (ORR) were 81% vs. 46% (P = 0.042), and PFS was NR vs. 13.9 months (P = 0.25), respectively. The most common grade 3–4 treatment-related adverse events were hypertriglyceridemia (8 [25%] of 32 patients) and hypercholesterolemia (5 [16%]). No treatment-related deaths occurred.

The study concluded that lorlatinib demonstrated durable clinical activity in TKI-naïve, advanced ROS1-positive NSCLC, including patients with CNS metastases. Adverse events were predominantly low grade and manageable for long-term use. Given its limited treatment alternatives, lorlatinib may be considered for earlier intervention in ROS1-positive NSCLC treatment strategies.

The trial was sponsored by National Cancer Center, Korea.

Source: https://meetings.asco.org/abstracts-presentations/232887

Clinical Trial: https://clinicaltrials.gov/study/NCT03612154

AHN B. C., Kim Y. J., Kim D. W., et al. (2024). “Lorlatinib in TKI naïve, advanced ROS1-positive non-small-cell lung cancer: A multicenter, open-label, single-arm, phase 2 trial.” Presented at ASCO 2024. J Clin Oncol 42, 2024 (suppl 16; abstr 8519), 10.1200/JCO.2024.42.16_suppl.8519

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