tbuckley/cabot-search huggingface dataset:
Impact of timing of immunotherapy in survival among patients with advanced lung adenocarcinoma treated with first-line immunochemotherapy: A propensity score matching.
Authors: Yanxin Sun, Leirong Wang, Yuping Sun, Qi Dang, Yihui Ge, Aiqin Gao, Qinglei Cheng, Haifeng Sun, Jian Zhang, Jiake Wu, Juan Li
Journal: Journal of Clinical Oncology (2024)

e20560 Background: Immunochemotherapy combinations have been the mainstream first-line standard treatment of advanced non-small cell lung cancer (NSCLC), wherein concurrent chemotherapy and immunotherapy are conventionally fixed to an established dosing regimen. Few studies had suggested the remarkable impact of the timing of immunotherapy on immunochemotherapy combined therapy. However, this issue has not been addressed in advanced NSCLC cohort. Methods: This study was a retrospective analysis of 532 patients with advanced lung adenocarcinoma (LUAD) without EGFR/ALK mutations who underwent immunochemotherapy as first-line systemic treatment between June 2018 to June 2022 at 3 facilities. Patients were divided into two groups (induced and non-induced) according to the different timing of immunotherapy in combined therapy, which defined induced as receiving 1 or more cycles of full-dose chemotherapy alone before concurrent immunochemotherapy. The bias between induced and non-induced groups was minimized with Propensity Score Matching (PSM). Patients outcomes, including progression-free survival (PFS) and overall survival (OS), were compared between the two groups by Kaplan-Meier survival curves and Cox regression analyses. Results: Survival analysis showed that both PFS and OS of the induced chemotherapy group patients were significantly longer than that of non-induced group (PFS: 14.63 months vs. 10.13 months, p = 0.004; OS: Not reached vs. 20.27 months, p = 0.0013). In the COX regression, after adjusting for confounders, induction chemotherapy was found to be a remarkable favorable factor for both PFS and OS (PFS: HR = 0.73, p= 0.018; OS: HR = 0.69, p= 0.034). After pretreatment features and treatment parameters were included in PSM, 104 patients were identified in each groups with matched characteristics, and moreover, the results of survival analysis remained consistent and showed significant difference between induced and non-induced group (PFS: 14.63 months vs. 10.23 months, p = 0.029; HR = 0.71, p= 0.030. OS: Not reached vs 18.27 months, p = 0.0013; HR = 0.52, p= 0.002). Conclusions: For advanced LUAD patients treated with first-line immunochemotherapy combinations, the timing of immunotherapy had significant impact on prognosis, which suggested notable benefit of induction chemotherapy before concurrent immunochemotherapy.
Dermatologic adverse events in EGFR-TKIs: A real-world analysis.
Authors: Emily Paton, Ryan Jeremy Friedman, Jeremy Paul Cetnar
Journal: Journal of Clinical Oncology (2024)

e20572 Background: Dermatologic adverse events (DAEs) affect a significant number of patients with non-small cell lung cancer (NSCLC) who are treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). While many DAEs have been identified during clinical trials and included in FDA drug labels, patients have raised concerns about experiencing unexpected DAEs. This study reviews the FDA Adverse Events Reporting System (FAERS) to identify DAEs in EGFR TKIs approved in NSCLC that are not included in drug labels. Methods: FAERS was queried for DAEs between 2003 – 2023 for osimertinib, afatinib, ertlotinib, gefitinib and mobocertinib. The reporting odds ratio (ROR) was calculated to compare DAEs between these EGFR-TKIs and all other drugs in the database. DAEs were considered statistically significant if the lower limit of the ROR 95% confidence interval (CI) was &gt; 1 and if there were ≥ 3 reported adverse reactions. Results: 67,480 adverse events were reported for the 5 EGFR-TKIs studied. DAEs constituted 30.3% (20,426) of all adverse event reports. We identified skin (skin fissures, eczema, lip swelling, and skin infection), nail (onychalgia and onychomadesis), and hair (abnormal hair growth and hair disorder) DAEs not previously included in EGFR-TKI drug labels. RORs with 95% CIs are summarized in the table. Conclusions: Real-world FAERS data complements clinical trial data in identifying specific DAEs affecting NSCLC patients treated with EGFR TKIs. Our findings highlight DAEs that were previously not described, aiding clinicians in educating patients about side effects and giving patients a more nuanced understanding of what to expect before undergoing treatment. [Table: see text]
Response to first-line therapies in metastatic lung adenocarcinoma with low PD-L1 expression: A multi-center retrospective study.
Authors: Yihui Ge, Aiqin Gao, Yuping Sun, Juan Li, Shuyun Wang, Jian Wang, Xiaojuan Wei, Leirong Wang, Qinglei Cheng, Xiufen Wang, Jian Zhang, Xuebing Fu
Journal: Journal of Clinical Oncology (2024)

e20574 Background: For metastatic lung adenocarcinoma with low PD-L1 expression (tumor proportion score:1-49%), chemotherapy in combination with immune checkpoint inhibitors (IC), with bevacizumab (BC), or with both (IBC) have been established as standard first-line options. However, the optimal scheme is still undetermined. Methods: This retrospective study enrolled 125 metastatic lung adenocarcinoma patients with low PD-L1 expression from four cancer centers. All the patients received IC, BC, or IBC as the first-line therapies. Propensity score matching (PSM) with a ratio of 1:1:1 was used to balance the inter-group clinical characteristics. Efficacy, including objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS), as well as safety were evaluated. Results: 35 of the 125 patients received IBC, 37 received BC, and 53 received IC. After PSM, a total of 35 pairs of patients were enrolled in the analysis. Patients receiving IBC (ORR: 57.1%, DCR:100%) or IC (ORR: 57.1%, DCR: 91.4%) obtained superior ORR and DCR in relative to those receiving BC (ORR: 45.7%, DCR: 82.9%). However, only IBC (median PFS: 20.47m; median OS: not research) rather than IC (median PFS: 10.0m; median OS: 21.36m) treatment generated significantly prolonged PFS and OS compared with BC (median PFS: 9.43m, P = 0.007; median OS: 23.2m, P = 0.048). We further analyzed the survival benefit based on different clinical and molecular features. We found patients with female gender had more significant OS benefit from IBC treatment over IC or BC treatment. In addition, non-smokers benefit more from IBC compared with IC. The occurrence of adverse events (AEs) was more frequent in IBC (74.3%) and IC (85.7%) group in relative to BC group (42.8%). Meanwhile, ≥ grade 3 AEs (22.9%) was markedly higher in IBC group compared with that in BC group (5.7%). However, leukopenia and neutropenia represent the most common ≥ grade 3 AEs, which are easy to be clinically managed. Conclusions: For metastatic lung adenocarcinoma patients with low PD-L1 expression, IBC is the preferred first-line therapy in terms of survival. However, the AEs should be carefully concerned.
PD-(L)1 inhibitors plus bevacizumab and chemotherapy as first-line therapy in PD-L1 negative metastatic lung adenocarcinoma: A real-world data.
Authors: Yihui Ge, Yuping Sun, Aiqin Gao, Juan Li, Dahai Wang, Jiake Wu, Yanxin Sun, Haifeng Sun, Haodong Sun, Jie Li
Journal: Journal of Clinical Oncology (2024)

e20577 Background: Chemotherapies combined with immune checkpoint inhibitors (ICIs) and/or bevacizumab (named IC, BC and IBC respectively) are the preferred first-line options for PD-L1 negative and oncogenic driver wild-type metastatic lung adenocarcinoma. However, the optimal strategy is still undetermined. Methods: This retrospective real-world study enrolled PD-L1 negative metastatic lung adenocarcinoma patients from four cancer centers between January 1, 2018 and June 30, 2022. All the patients received IC, BC, or IBC as the first-line therapies. The efficacy and safety were evaluated. Results: A total of 205 patients were included, with 60, 83, and 62 patients in IC, BC, and IBC groups, respectively. Patients receiving IBC obtained the highest objective response rate (ORR) (43.5%) and disease control rate (DCR) (100%) relative to those receiving IC (40.4%, 84.2%) or BC (40.5%, 96.2%). Compared with the IC (6.74m) or BC (8.28m) group, IBC group improved significantly median progression-free survival (mPFS) (9.53m, P = 0.005). However, the difference in overall survival (OS) were not observed among the three groups. When analyzed based on different clinical and molecular information, we found that male gender, ever smoking, wild-type genes, and adrenal metastasis predicts superior PFS benefit when treated with IBC. In patients with liver metastasis, IBC or BC treatment achieved better PFS compared with IC. No additional adverse reactions were observed in IBC group compared with other two groups. Conclusions: Combined IBC treatment achieved superior DCR and PFS compared with IC or BC treatment in patients with PD-L1 negative metastatic lung adenocarcinoma, while did not increase the adverse events.
Cost-effectiveness of sotorasib as a second-line treatment for non-small cell lung cancer with KRAS<sup>G12C</sup> mutation in China and the US.
Authors: 亚宁 朱, Peng Zhāng, Nong Xu
Journal: Journal of Clinical Oncology (2024)

e20567 Background: Sotorasib was used for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer with KRAS G12C mutation who had received at least one systematic therapy, showing good antitumor activity and safety. However, it was unclear whether the high-cost sotorasib was cost-effective. Methods: A Markov model was developed to compare the lifetime cost and efficacy of sotorasib to treat non-small cell lung cancer with KRAS G12C mutation from the CodeBreak 200 randomized placebo-controlled trial, which included 345 patients with previously treated non-small cell lung cancer with KRAS G12C mutation. Incremental cost-effectiveness ratio(ICER), quality-adjusted life-year (QALY), incremental QALY were calculated for the 2 treatment strategies. One-way sensitivity analysis was used to investigate the factors that had a greater impact on the model results, and tornado diagram was used to verify the model stability, probabilistic sensitivity analysis was performed by Monte Carlo simulation, random factors were introduced into the model to simulate a certain number of large samples, and the results were presented as cost-effectiveness acceptable curves. Results: This economic evaluation of data from the CodeBreak 200 randomized trial. In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59. Compwered with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than WTP, so sotorasib had no economic advantage. In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50 /QALY, which was low than WTP, indicating that the increased cost of sotorasib was acceptable. Conclusions: Sotorasib had cost effect from the perspective of the US. Howere, sotorasib had no cost effect from the perspective of China, and only when the willingness to pay(WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0 to 49%.
Pre-treatment CT radiomics for predicting immunotherapy response in non-small cell lung cancer(NSCLC): RECIST vs. irRECIST criteria.
Authors: Monica Yadav, Jeeyeon Lee, Haseok Kim, Seyoung Lee, Taegyu Um, Salie Lee, Trie Arni Djunadi, Liam IL-Young Chung, Jisang Yu, Darren Rodrigues, Nicolo Gennaro, Leeseul Kim, Myungwoo Nam, Yuchan Kim, Ilene Hong, Jessica Jang, Grace Kang, Amy Cho, Yury Velichko, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

e20613 Background: Accurate prediction of how patients with non-small cell lung cancer (NSCLC) will respond to immunotherapy is essential for customizing individual treatment plans. This research explores the use of radiomics analysis from pre-treatment CT scans as a method to predict the effectiveness of immunotherapy in individuals with NSCLC. Methods: This IRB-approved retrospective study investigated radiologic and clinical data from 159 patients with stage III-IV NSCLC treated with immunotherapy. Imaging responses were assessed according to RECIST 1.1 and immune-related RECIST (irRECIST) criteria at least twice during a 24-week period. Responses were categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). 3D radiomics features were extracted from both the tumor and a 1 cm thick peritumoral region. A linear mixed-effect harmonization model was employed to correct for scanner-associated variations. A Random Forest algorithm was used to develop a classification model to predict response according to RECIST 1.1 or irRECIST. The dataset was split into training (70%) and test (30%) sets. The accuracy of predictions was evaluated using confusion matrix statistics and bootstrapping with 1,000 iterations for median and 95% confidence interval (CI). Results: Using RECIST 1.1 criteria, 41 patients (25.2%) achieved PR and CR(0.6), 62 (39.0%) achieved SD, and 56 (35.2%) achieved PD. IrRECIST criteria yielded slightly higher CR/PR rates with 52 patients (32.7%), while SD decreased to 65 (41.0%) and PD remained at 42 (26.4%). For predicting CR/PR and SD responses, the models achieved a sensitivity of 0.45 (95% CI: 0.38-0.50) and 0.64 (0.60-0.68) for irRECIST, compared to 0.34 (0.28-0.38) and 0.55 (0.52-0.60) for RECIST 1.1. The corresponding specificity was 0.85 (0.83-0.87) and 0.63 (0.59-0.67) for irRECIST, compared to 0.91 (0.89-0.93) and 0.67 (0.63-0.72) for RECIST 1.1. For predicting PD response, the models achieved a sensitivity of 0.49 (0.45-0.56) for irRECIST and 0.57 (0.52-0.62) for RECIST 1.1. The models' balanced accuracy for predicting CR/PR, SD, and PD were 0.65 (0.61-0.68), 0.64 (0.61-0.67), and 0.65 (0.63-0.69) for irRECIST, compared to 0.62 (0.59-0.64), 0.61 (0.59-0.64), and 0.62 (0.59-0.64) for RECIST 1.1, respectively. Conclusions: This study demonstrates the potential of pre-treatment CT radiomics to predict immunotherapy responses in NSCLC patients, offering insights into personalized treatment approaches. However, larger studies are needed to validate our findings.
First- and second-line biomarker utilization in non-small cell lung cancer.
Authors: Matthew Leong, Mahzad Azimpouran, Audrey McCloskey, Kamya Sankar, Eric Vail
Journal: Journal of Clinical Oncology (2024)

e20564 Background: Targeted therapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) since FDA-approval of the first EGFR-inhibitor in 2003. While number of actionable mutations and FDA-approved therapies has drastically increased, numerous studies have reported lackluster utilization rate of these therapies. Many of these studies take place in the community setting and focus on first line targeted therapy utilization. We aim to investigate the utilization rate of targeted therapies in an academic center, as well as explore utilization rate of newer second line therapies. Methods: The pathology database was queried for all stages of NSCLC cases with molecular testing (including qPCR, FISH, and NGS) from Jan 2016-Jan 2024. Patients with actionable alterations in EGFR, ALK, ROS1, BRAF, MET, RET, NTRK, KRAS, and ERBB2 ( HER2) that were detected six months prior to the first FDA approval for their respective targeted therapy were included. Patients who were lost to follow-up, those with early-stage non-metastatic tumors, or without progression on first line therapy at time of data cutoff (for actionable mutations with approved targeted second-line treatment) were subsequently excluded. Therapy plans and clinical course for the remaining patients were reviewed. Results: 355 NSCLC patients with actionable mutations were identified (210 EGFR, 63 ALK, 15 BRAF, 18 ROS1, 6 RET, 26 MET, 1 NTRK, 17 KRAS, 0 ERBB2). The following patients received an FDA-approved targeted first line therapy: EGFR (non-exon 20 insertion) 194/207 (94%), BRAF 8/15 (53%), ALK 60/63 (95%), ROS116/18 (89%), RET 5/6 (83%), MET 22/26 (85%), and NTRK 1/1 (100%). For FDA-approved second line therapy, KRAS 10/17 (59%) and EGFR (exon20 insertion) 2/3 (67%) patients received targeted therapy. No ERBB2 patients progressed. There was statistically significant difference between treatment rates between BRAF and non- BRAF first line therapies (p &lt; .0002) and between rates of treatment with first and second line therapies (p &lt; .0002). For those that did not receive eligible therapy, 15/37 (41%) received chemotherapy or immunotherapy treatment and 20/37 (54%) were too clinically severe for treatment. Conclusions: Despite most eligible patients receiving the appropriate targeted therapy (89%), there remains distinct subsets with significantly lower treatment rates. In particular, there is a large gap in treatment between the FDA-approved first and second line therapies as well as patients with BRAF mutations compared to other first line therapies. While the overall treatment rate based on molecular findings are higher than those reported from community settings, there remains patient populations which seemingly have their molecular findings overlooked. [Table: see text]
Current status of PD-(L)1 inhibitor usage in advanced or metastatic non-small cell lung cancer: A national survey of oncologists in China.
Authors: Baocheng Wang, Caicun Zhou, Jun Wang, Jie Hu, Jianchun Duan, Yu Yao, Guohui Li, Yun Fan, Cheng Huang, Qian Chu, Chunling Liu, Lihua Liu, Zhiyong Ma, Yueyin Pan, ChunXia Su, Yongqian Shu, Yongsheng Wang, Chengzhi Zhou, Mingfang Zhao, Xiaotao Zhang
Journal: Journal of Clinical Oncology (2024)

e20559 Background: The aim of the present study conducted by Chinese Society of Clinical Oncology Expert Committee on Immunotherapy was to obtain real-world information on the use of PD-(L)1 inhibitors for non-small cell lung cancer (NSCLC) in different regions of China via a national questionnaire survey for oncologists. Methods: This survey was distributed online to cancer-related medical departments in 202 first-tier to fourth-tier cities of China between March to April 2023. The national survey consisted of four sections regarding oncologists’ concerns about immunotherapy as follows: treatment choice, response assessment, treatment duration, and management of immune-related adverse events (irAEs). Results: A total of 2,018 oncologists completed this survey. For advanced squamous (SQ) and non-squamous (NSQ) NSCLC without targetable genetic alterations, PD-(L)1 inhibitor-based regimens were the most widely used first-line treatment regimen (SQ: 52%, NSQ: 46%), followed by chemotherapy alone (SQ: 37%, NSQ: 37%) and other regimens (SQ: 11%, NSQ: 17%). The average treatment duration of 1L PD-(L)1 inhibitor-based regimens in SQ NSCLC and NSQ NSCLC were 6.4 and 6.2 cycles, respectively. 67% of oncologists may discontinue immunotherapy or change regimens when the first radiographic tumor assessment was SD per RECIST 1.1. Other reasons for early discontinuation of PD-(L)1 inhibitors before PD or unacceptable toxicity included economic reasons (78%) and patients’ low willingness to continue immunotherapy even they reached CR/PR (62%). Oncologists in the second-tier cities and below were more likely to discontinue immunotherapy when the tumors were stable, with shorter treatment duration of 5.7 cycles versus 7.1 cycles in the first-tier cities. The most common irAEs included dermatologic, endocrine, pulmonary, gastrointestinal, and hepatic toxicities. Conclusions: PD-(L)1 inhibitor-based regimens have become the priority choice for advanced NSCLC in China, however, the status of standardized continuous use of immunotherapy is obviously insufficient. There is a gap between clinical practice and clinical trials regarding PD-(L)1 inhibitor usage, which need more attention. [Table: see text]
Are the results of clinical trials in patients with NSCLC reflected in real life? The Registurk-Lung study.
Authors: Mehmet Artac, Mahmut Emre Yildirim, Ahmet Taner Sümbül, Akin Ozturk, Nuri Karadurmus, Lokman Koral, Umut Demirci, Cagatay Arslan, Mahmut Gumus, Umut Kefeli, Ozlem Ercelep, Sinemis Celik, Oktay Bozkurt, Bala Basak Oven, Erdem Cubukcu, Mustafa Karaca, Ahmet Bilici, Deniz Tural, Hakan Harputluoglu, Faysal Dane
Journal: Journal of Clinical Oncology (2024)

e20512 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. Methods: In our country, within the scope of the Registurk-Lung observational study (NCT05254119), a total of 4250 patients without driver mutation, metastatic non-small cell lung cancer were recorded 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: 4250 patients were evaluated. The median age was 64 (26-90) years and 15.1% of the patients were female. The proportion of patients who never smoked was 10.4 %. Histopathologically, 36.4% of the patients were diagnosed with squamous cell carcinoma. PDL-1 level was higher than 50% in 24.0% of patients and &lt; 1 in 40.4% of patients. Only 11.8 percent of patients received single agent immunotherapy or chemoimmunotherapy. Other patients had received only a combination of doublet chemotherapy. The PFS was 6.9 months (95% CI: 6.4-7.3) and OS 14.6 (95% CI: 12.3-16.8) months in the whole patient group. Compared to the group that received chemotherapy alone, PFS and overall survival were longer in the group that received chemoimmunotherapy. This difference between the two groups was found to be statistically significant (p:0,001 and 0,031 respectively). Conclusions: As shown in clinical studies, immunotherapy alone or chemoimmunotherapy according to PDL-1 expression status provides a significant survival contribution compared to chemotherapy alone.