bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical outcomes with frontline immunotherapy (IO) in BRAF-mutant NSCLC.
Authors: Marin-Acevedo Julian A. , Thapa Ram , Puri Sonam , Hicks James Kevin , Gray Jhanelle Elaine 
Published: June 2023

e21089 Background: Oncogenic BRAF mutations are present in approximately 4% of non-small cell lung cancers (NSCLC). They are categorized as class I, II, or III according to their effect on the MAPK pathway. Little is known about how oncogenic BRAF mutations influence tumor PD-L1 expression and response to IO. We evaluated the clinical outcomes of frontline IO among BRAF classes. Methods: We performed a retrospective analysis of patients with BR AF-mutant NSCLC from January 1, 2012 through March 30, 2020. BRAF mutations were detected using next-generation sequencing or genotyping methods. PD-L1 expression was assessed using 22C3 or SP263 assays. Patient demographics were collected through electronic medical records review. In those with advanced/metastatic disease, we captured response to anticancer therapies using standardized real-world (rw) criteria and calculated rwOS using Kaplan-Meier method with log-rank test. Results: Of all 9,004 lung cancer patients (all histologies) with genotyping testing, 79 had NSCLC and an oncogenic BRAF mutation. 52% were females, 95% had adenocarcinoma, 81% were active/former smokers, and 76% had PD-L1 ≥1%. 39 patients had class I, 24 had class II, and 16 had class III mutations. Of these, 43 patients had advanced/metastatic disease evaluable for response. Patients with class I mutations who received first-line IO trended towards improved rwOS (42.6 months) vs. frontline anti-BRAF therapy (22.7 months; p= 0.51) and chemotherapy (19.6 months; p= 0.63). Patients with non-class I mutations, also trended towards improved rwOS with frontline IO (18.8 months) compared to frontline chemotherapy (9.9 months; p= 0.25). Outcomes were better in all patients with PD-L1 levels ≥1% and ≥50% who received IO. Patients with non-class I variants tended to have shorter rwOS with IO or chemotherapy compared to those with class I mutations (Table 1). Despite an overall trend towards improved outcomes with first-line IO, results did not reach significance likely due to the limited number of evaluable patients. Conclusions: The use of frontline IO may be associated with better outcomes than frontline chemotherapy or targeted therapies in patients with BRAF-mutant NSCLC. Patients with class I mutations and/or higher tumor PD-L1 expression seem to derive the most benefit. [Table: see text]
Evaluation of the prevalence of MET and protein tyrosine kinase 7 expression in non-small cell lung cancer to evaluate overlap of ADC antigens.
Authors: Ansell Peter J. , Camidge D. Ross , Baijal Shobhit , Xia Xiaoyu , Vasilopoulos Athanasios , Li Martha , Seshadri Ramya , Arvanitis Leonidas , Lindsey Sidney S. , Cai Mona H. , Choi Yookyung Christy , Ratajczak Christine , Jeng Edwin E. , Gruber Stephen B. , Lu Shun 
Published: June 2023

e21105 Background: Biomarker-targeted antibody-drug conjugates (ADCs) have shown promise in treating lung cancer. Telisotuzumab vedotin (Teliso-V; ABBV-399) is a first-in-class MET (also known as c-Met)-directed ADC comprising the monoclonal antibody telisotuzumab (ABT-700) conjugated to a cytotoxic microtubule inhibitor, monomethyl auristatin E (MMAE), via a cleavable dipeptide linker. In the phase 2 LUMINOSITY study (NCT03539536), Teliso-V demonstrated promising anticancer activity in previously treated patients with MET-overexpressing (OE), non-squamous epidermal growth factor receptor wild type ( EGFR WT) non-small cell lung cancer (NSCLC; 52.2% overall response rate in MET OE high group, 36.5% in all MET OE cohort [intermediate and high]) and an acceptable safety profile (Camidge et al. J Clin Oncol. 2022;40:16 suppl, 9016). These data provide proof of concept that biomarker-selected MMAE-based ADCs could be beneficial to patients with NSCLC. Cofetuzumab pelidotin (ABBV-647), an ADC with a similar composition to Teliso-V, contains an anti-protein tyrosine kinase 7 (PTK7) monoclonal antibody (hu6MO24) conjugated to a microtubule-inhibiting cytotoxin, Aur0101 auristatin, via a cleavable cysteine-reactive linker. PTK7 expression and oncogenic functions have been reported in several cancers. We sought to establish the co-prevalence of MET OE and PTK7 in NSCLC to understand if both these antigens targeted by ADCs are co-expressed or present in distinct tumors. Methods: Antigen prevalence was analyzed in tumor samples from patients at the City of Hope National Medical Center with non-squamous NSCLC and EGFR WT or unknown status. Immunohistochemistry (IHC) assays used were MET (SP44) Assay for MET OE (Roche Tissue Diagnostics; positive if ≥25% cells at 3+ intensity) and an AbbVie-developed assay for PTK7 expression (positive if ≥90% cells at ≥2+ intensity). Results: A total of 148 patients (median age 67 years, 52% stage ≥III at diagnosis, 68% ECOG 0–2) were screened (data shown in table). About 24% of the patients were MET IHC positive, whereas 11% were PTK7 IHC positive. Further, MET OE and PTK7 had complementary prevalence with only 3% of the patients co-expressing both antigens. Conclusions: MET OE and PTK7 expression by IHC were found to be complementary in patients with non-squamous EGFR WT/unknown NSCLC. About 32% of patients were positive for MET OE or PTK7 expression or both. Data represent patients from a single center and more pre-treatment tissue samples that were viable and available. These IHC findings suggest that MET OE and PTK7 are indeed complementary NSCLC biomarkers. [Table: see text]
Clinical trial versus standard of care in EGFR-wild type and ALK- negative lung adenocarcinoma: A propensity-matched analysis.
Authors: Jung Hyun Ae , Park Boram , Park Sehhoon , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju 
Published: June 2023

e21116 Background: Clinical trials have been a vital role for survival improvement in recurrent or metastatic lung cancer. Recent advances in targeted therapy for EGFR-mutant or ALK-positive lung adenocarcinoma dramatically increased survival. However, EGFR-wild type and ALK negative lung adenocarcinoma still had relatively poor survival outcome. Clinical trial of targeted therapy for rare driver mutation or immunotherapy was introduced in 2015. Moreover, next-generation sequencing was reimbursed in 2017 in Korea. This study evaluated the benefit of clinical trials for EGFR-wild type and ALK negative lung adenocarcinoma in recent 5 years. Methods: This study included patients with recurrent or metastatic lung adenocarcinoma who received systemic treatment between March 2017 and June 2022 at Samsung Medical Center. We compared overall survival in group with clinical trial and the standard of care (SOC) by using propensity score matching (PSM) (1:1). We used cox proportional hazard models to calculate the hazard ratio (HR) and 95% confidence interval while accounting for clustering among matched pairs. Results: Of total, 1,686 EGFR-wild type and ALK negative lung adenocarcinoma were included for final analysis. Among them, 1,380 received SOC only and 306 patients enrolled at least one clinical trial. In a group of clinical trial, 41.5%, 29.1%, and 23,2% of patients were enrolled for first-, second-, and third-line treatment, respectively. To achieve the balance between the SOC group and the clinical trial group, 8 baseline characteristics (age, sex, smoking history, ECOG performance status, brain metastasis, liver metastasis, bone metastasis, and rare driver mutation) were included. After PSM, 612 patients were matched to group of the SOC (n = 306) and the group of clinical trial (n = 306). Among the clinical trial, 27.8% was a clinical trial of targeted therapy and 72.2% was a clinical trial of immunotherapy or others. Median follow-up duration was 32.8 months (range, 5.0–64.4). Median overall survival was 17.1 months (95% CI, 13.2–21.4) for SOC and 27.3 months (95% CI, 22.1–32.4) for group of clinical trial (HR = 0.71 (95% CI, 0.58–0.88, P = 0.002). Conclusions: This study showed the performance of clinical trials for patients with EGFR-wild type and ALK-negative lung adenocarcinoma at tertiary hospital. After PSM, clinical trials showed survival benefits that reduced the risk of death by 29% in patients with EGFR-wild type and ALK-negative lung adenocarcinoma.
Correlation of homologous recombination deficiency (HRD) score with response to the first-line treatment of immune checkpoint inhibitors plus chemotherapy in non-small cell lung cancer.
Authors: Li Guo , Zeng Lili , Wang Lingling , Cai Yuhang , Xuan Chenghao , Zhong Dian-Sheng , Zhang Linlin 
Published: June 2023

e21121 Background: Homologous recombination (HR) gene mutations were reported to be associated with efficiency of immune checkpoint inhibitors (ICIs). However, up to date, no recognized standard has been set up for definition of HR mutation (+), which limited its clinical application. Homologous recombination deficiency (HRD) score reflects genomic scar induced by HR genes alteration and disfunction. Thus, it may be worth to explore whether HRD score could predict the efficacy of ICIs-based therapy. Methods: We collected tumor tissues from metastatic non-small cell lung cancer (NSCLC) patients who received first-line treatment of ICIs combined with platinum-based chemotherapy. HRD score testing were carried by BGI genomic scar analysis kit, which calculates the sum of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), large-scale state transitions (LST) scores, and corrected by ploidy of tumor samples, through next generation sequencing(NGS) data. The association of HRD score and response to ICIs plus chemotherapy were analyzed. Results: 22 EGFR/ALK wild-type metastatic NSCLC patients were included. The average HRD score was 24.57, varying from -26.37 to 92.34. Threshold traversal was performed based on analysis of the progression free survival (PFS) data from the included NSCLC patients. HRD score 31 or more were define as HRD (+). Kaplan-Meier PFS Survival analysis showed prolonged median PFS (mPFS) in HRD (+) versus HRD (-) NSCLC patients (N/A vs. 7.0 ms, Log-rank P = 0.029; HR 0.20, 95%CI 0.04-0.96, likelihood-ratio P = 0.03). The objective response rate (ORR) was 45.5% (5/11) in HRD(+) versus 27.2% (3/11) in HRD(-) patients. In patients with PD-L1 TPS≥1% (22C3), the mPFS was N/A vs. N/A, and the ORR was 75.0% (3/4) vs. 37.5% (3/8), in HRD (+) vs. HRD(-) patients. In patients with PD-L1 TPS < 1% (22C3), the mPFS was 8.5 ms vs.2.0 ms (Log-rank P = 0.0085; HR 0.08, 95%CI 0.01-0.82, likelihood-ratio P = 0.02), and the ORR were 28.6% (2/7) vs. 0%(0/3), in HRD (+) vs. HRD(-) patients. Conclusions: In addition to PD-L1 expression level, HRD score would be a potential promising biomarker for predicting the efficiency of ICIs plus platinum-based chemotherapy in NSCLC patients.
Effect and safety of combining bevacizumab and fractionated stereotactic radiotherapy for brain metastases in patients with non-small cell lung cancer: A phase II trial.
Authors: Zhou Rui , Zheng ShiYang , Huo LanQing , Luo QiaoTing , Wang DaQuan , Guo JinYu , Liu BiaoShui , Zhang Jun , Wang Bin , Qiu Bo , Liu Hui 
Published: June 2023

e21132 Background: W e aimed to assess the efficacy and safety of c ombining b evacizumab and fractionated stereotactic radiotherapy ( FSRT ) for brain metastases (BMs) in non-small cell lung cancer ( NSCLC ) patients with stable extracranial disease status in this study. Methods: NSCLC patients with BMs were recruited between J anuary 20 20 and J anuary 202 2 . P atients were assigned to receive FSRT of 40Gy in 10 fractions (BED 56eGy) or 30Gy in 5 fractions (BED 48eGy). Meanwhile, bevacizumab was administered before FSRT (d1) and after FSRT (d21) with a dosage of 7.5mg/Kg. The primary endpoint of the study is intra-cranial progression-free survival (IPFS) . The secondary endpoints contained overall survival (OS), progression-free survival (PFS) , quality of life (QOL) score and toxicities. All time-to-event endpoints (IPFS, OS and PFS) were measured from the end of radiotherapy. Results: From J anuary 2020 and J anuary 202 2, 108 patients were recruited with a median follow-up duration was 15.2 months . The 1-year IPFS and OS rate were 82.9% ( 95% confidence interval (CI), 79.6%-86.2% ) and 80.4% ( 95% CI, 76.8%-84.0% ), respectively . The median PFS was 15.0 months ( 95% CI, 9.50-20.50 months ). The median IPFS and OS had not been reached at the time of the last follow-up. The treatment-related toxicities were mild with low incidence. Reversible mild hypertension and cerebral radio-necrosis were observed in 2 and 1 patients, respectively. No signs of ex tra-lesional haemorrhage and progression of peri-lesional oedema was found during the assessment period of treatment response. More importantly, significant improvent of QOL was observed in symptomatic patients. Conclusions: The combination of FSRT with bevacizumab in patients with NSCLC was well tolerated and achieved promising intracranial disease control. Patients maintained satisfactory QOL after receiving the combined regimen with low incidence of cerebral radio-necrosis. Clinical trial information: NCT04345146 .
Association between body mass index and survival outcomes for patients with advanced non–small-cell lung cancer treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
Authors: Sun Yanxin , Sun Yuping , Li Juan , Gao Aiqin 
Published: June 2023

e21136 Background: Growing researches have focused on obesity as an useful prognostic factor for pan-cancer patients with immmnotherapy. The role of body-mass index (BMI) in predicting response to ICIs is not consistent in different tumors. This meta-analysis was conducted to evaluate the relationship between BMI and outcome in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors, which is not clear as studies have demonstrated inconsistent results and significant interpretation biases. Methods: We searched PubMed and Embase, for relevant studies published up to December 2022. Title/abstract screening, full-text review, data extraction, and quality assessment were performed independently. Results: The correlation between BMI and prognosis in patients with advanced non-small cell lung cancer treated with ICIs was compared in ten trials encompassing 5000 individuals with the disease. The findings showedthat immunotherapy was significantly more effective for non-small cell lung cancer patients with a higher BMI compared to those with a lower BMI (OS: HR: 0.832, 95% CI: 0.725-0.955, p = 0.009; PFS: HR: 0.860, 95% CI: 0.771-0.960, p = 0.007). While，in the investigation of the obese group, no statistically significant differences were found. Conclusions: In patients with advanced non-small cell lung cancer treated with ICIs, appropriate higher BMI was significantly linked to better outcomes. However, discrepant findings from different cutoff subgroup analyses urgently call for further analysis.
Role of synthetic lethal mutations for the immune response: Exploratory studies of two non-small cell lung cancer cohorts and two pan-cancer cohorts.
Authors: Wang Jun , Liu Miao , Zhang Ding 
Published: June 2023

e21137 Background: Synthetic lethality (SL) is a phenomenon in which mutations in either of two genes do not affect cell survival, but abnormalities in both genes lead to cell death. However, it is little known whether synthetic lethality affects the response of immunotherapy. Methods: Synthetic lethal gene pairs come from the SynLethDB database, which provides a webserver to calculate the confidence scores for each SL pair by integrating individual scores derived from different evidence sources. The analysis included two immunotherapy cohorts of non-small cell lung cancer (Chan, 2015 and Hellmann, 2018) and two solid tumor cohorts (Morris, 2019 and Berger, 2020) in the published literature. Synthetic lethal gene pairs were defined as genes with a score > 0.5. The patients with synthetic lethal gene pairs were divided into one subgroup (SL group), and the other patients were divided into another subgroup (non-SL group). Kaplan-Meier analysis was used to determine progression-free (PFS) and overall survival (OS). Results: Overall, four public cohorts with 12271 patients were included in the analysis. In the cohort of Chan 2015, a total of 34 patients with non-small cell lung cancer (NSCLC) received immunotherapy. Among them, 21 patients were in the SL group and 13 were in the non-SL group, with the former having a significantly longer PFS (p = 0.0345). In the other cohort of immunotherapy (Hellmann, 2018), 90 (37.5%) patients with NSCLC were in SL group. PFS for patients with SL group was significantly longer than those in non-SL group (p = 0.0261). In cohorts with pan-cancer, patients in Morris 2019 cohort (n = 1661) received immunotherapy and patients in Berger 2020 cohort (n = 10336) received other kinds of treatment. A better prognosis was observed in patients with the immunotherapy in SL group than non-SL group (p < 0.0001). In contrast, patients with other kinds of treatment had a significantly worse prognosis in SL group than non-SL group (p < 0.0001). Conclusions: Our results suggested that synthetic lethal gene pairs containing scores greater than 0.5 may be associated with higher progression-free survival in patients with various types of tumors. The specific reasons for the impact still need to be further explored.
Pyrotinib plus antiangiogenic agents for HER2-altered advanced non-small cell lung cancer: A retrospective real-world study.
Authors: Yang Yaning , Yang Guangjian , Wang Yan 
Published: June 2023

e21141 Background: Although some targeted therapies have been shown to be effective in treating HER2-altered non-small cell lung cancer (NSCLC), the survival demands have not yet been met due to the high cost and limited availability. This study aimed to assess the effectiveness and safety of pyrotinib plus antiangiogenic agents, including apatinib, anlotinib, and bevacizumab in previously treated patients with HER2-altered advanced NSCLC. Methods: In this retrospective real-world study, patients with HER2-altered NSCLC who received pyrotinib plus antiangiogenic agents as second or later-line treatment between November 2015 and January 2022 were reviewed. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety profiles of patients were analyzed. Results: A total of 107 patients were included in the analysis. Fifty-nine patients (55.1%) have received at least two lines of prior chemotherapy or HER2-targeted regimens. Most of them (87.9%) were identified as HER2 exon 20 insertions. At the data cutoff date (May 13, 2022), the ORR, DCR, median PFS, and median OS were 19.6% (21/107), 94.4% (101/107), 7.13 months (95% confidence interval [CI]: 6.26-8.01), and 19.50 months (95%CI: 12.83-26.17), respectively. There was no difference in the PFS between patients receiving apatinib or anlotinib/bevacizumab (median PFS, 7.13 months vs. 6.27 months, hazard ratio [HR] = 1.49, 95%CI: 0.87-2.54, P = 0.15). The most frequent grade 3 or higher treatment-related adverse events was diarrhoea (17.6%), followed by hypertension (11.0%) and nausea (3.3%). No treatment-related death occurred. Conclusions: Pyrotinib plus antiangiogenic agents demonstrated promising antitumor activity and a manageable safety profile in HER2-altered NSCLC patients.
First-line pembrolizumab plus platinum-pemetrexed in metastatic non-small cell lung cancer: Clinical experience in a Spanish tertiary hospital.
Authors: Lombardero Lara , De Elejoste Ibone , Casas Raquel , Azcuna Josune , Ortega Berezi , Mohamed Lamin Failah , Jiménez Labaig Pablo , Rubio Itziar , Munoz Llarena Alberto , Azkona Eider 
Published: June 2023

e21142 Background: In the phase III trial KEYNOTE-189 first-line pembrolizumab (pembro) plus platinum-pemetrexed (pem) significantly improved OS and PFS in metastatic nonsquamous non-small cell lung cancer (NSCLC) without EGFR/ALK alterations. We report outcomes of real-world patients (pts) treated with first line pembro plus platinum-pem in our hospital. Methods: We have done a descriptive, retrospective, single center study developed in a Spanish tertiary hospital where patients with metastatic nonsquamous NSCLC treated with first-line pembro plus platinum-pem have been included. SPSS v23 software has been used to analyze clinical data for OS and PFS using the Kaplan-Meier method. PFS-2, defined as time from first treatment to objective tumor progression on next-line treatment or death from any cause, whichever occurred first, was also recorded using the Kaplan-Meier method. Adverse events (AEs) were graded according to CTCAE v5.0. Results: From December 2019 to May 2022, 79 pts (67.1% M, 26% W; 64y median age, ECOG 0, 1, 2: 5.1%; 88.6% and 6.3%; PD-L1 < 1% 36 [45.6%], PD-L1 1-49% 37 [36.8%], PD-L1 50% 3 [3.8%]; unknown PD-L1 3 [3.8%]; 95% adenocarcinoma) were assessed. After a median follow-up of 19 months, OS was 17 months (5.3-28.7). Stratified by PD-L1 expression, mOS was 9 months (6.3 -11.7) in PD-L1 < 1%; 25 months in PD-L1 1-49%, NR in the rest. Median PFS was 9 months (5.8-12.2). According to PD-L1 expression, mPFS was 6 months (4.6 - 7.4) in PD-L1 < 1%; 19 months (8.7 - 29.2) PD-L1 1-49% and 7 months (0.6 - 13.4) in PD-L1 50%. PFS-2 was 17 months (10.7 - 23.3). At the time of the cut off 66 pts (83.5%) had discontinued treatment: 35 (53%) due to progression, 23 (34.8%) due to toxicity; 2 (3%) due to both, and 6 (9.1%) due to other reasons. Grade 3-5 AEs were observed in 35/79 pts (44.3%). 15.2% pts needed dose-reduction and 32.6% glucocorticoids. Conclusions: First-line treatment with pembro plus platinum-pem has demonstrated benefit in terms of OS, PFS and PFS-2 with tolerable adverse effects. The results obtained in our hospital, taken together, are consistent with those published in KEYNOTE-189 trial. However, the survival of our pts with PD-L1 < 1% seems to be poorer. This finding could be explained by the short median follow-up, low number of patients and differences in baseline demographic characteristics.