bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences in prognostic utility of peripheral eosinophil count in first-line immune checkpoint therapy against metastatic NSCLC.
Authors: Kwon Hyunwoo , Li Mingjia , Chian Kenneth , Gauntner Timothy , Jones Nicholas , Khorasanchi Adam , Spakowicz Daniel , Lopez Gabrielle , Goodyear Evelyn , Secor Austin , He Kai , Alahmadi Asrar , Memmott Regan Michelle , Kaufman Jacob , Shields Peter G. , Carbone David Paul , Otterson Gregory Alan , Presley Carolyn J , Li Zihai , Owen Dwight Hall 
Published: June 2023

9067 Background: To date, few studies have associated elevated Absolute Eosinophil Count (AEC) with improved outcome to a single agent immune checkpoint inhibitor (ICI) as first or subsequent line of therapy in patients with NSCLC. Here, we investigated prognostic utility of AEC and the sex difference in patients undergoing standard-of-care first-line ICI with or without chemotherapy for metastatic NSCLC. Methods: This was a retrospective cohort study of 310 patients with Stage IV NSCLC treated with first-line ICI-based therapies (alone or in combination with chemotherapy) under IRB approved protocol 2021C0069. Demographic data are summarized in the table. Peripheral AEC measured by cells/microL was collected within 1 week before the start of therapy. Eosinophil count was evaluated in males and females by both descriptive statistics and Chi-squared test as a continuous and categorical variable, respectively. High level of baseline AEC was defined as 75th percentile (270 cells/microL). Overall Survival (OS) was plotted using the Kaplan-Meier method and p-values from log-rank test were reported. PD‐L1 was assessed by tumor proportion score (TPS) and classified into < 1%, 1 to 49% and ≥ 50%. Results: 14% male vs 6% female patients were found to have peripheral eosinophilia (AEC ≥ 500) at the start of immunotherapy, p = 0.02. Patients with lower AEC had a median OS of 18.6 months vs 29.3 months in those with higher AEC ( p = 0.02, HR: 1.465, 95% Cl: 1.073-2.001). Patients with higher baseline AEC showed a sex difference, with median OS of 23.9 months in males vs NR median OS in females with over 60% survival at the time of last follow up ( p = 0.04, HR: 1.934, 95% Cl: 1.040-3.597). This difference was seen with ICI monotherapy ( p = 0.02, HR: 2.630, 95% Cl: 1.192-5.805), but not ICI with chemotherapy ( p = 0.83, HR: 1.116, 95% Cl: 0.4054-3.070). Higher AEC was associated with TPS ≥ 50% in both males and females ( p = 0.004 and 0.001, respectively), though no significant sex difference was observed. Conclusions: Our data highlight critical sex differences in interpretation of baseline AEC in patients on ICI therapy for metastatic NSCLC. While males have a higher frequency of peripheral eosinophilia, higher AEC correlates to improved OS predominantly in females. Further, this female-biased outcome is seen only with ICI monotherapy, even though higher AEC is associated with high PD-L1 expression in both sexes. Future studies are indicated to assess the longitudinal trend in eosinophil count as well as their active versus passive role in anti-tumor immunity and toxicity in the presence or absence of chemotherapy. [Table: see text]
A biomarker study of atezolizumab (atezo) + bevacizumab (bev) + carboplatin (carbo) + paclitaxel (pac) (ABCP) for patients with NSCLC harboring EGFR mutations (EGFRm) after failure of TKI therapy: NEJ043.
Authors: Watanabe Satoshi , Furuya Naoki , Nakamura Atsushi , Shiihara Jun , Nakachi Ichiro , Tanaka Hisashi , Nakao Mika , Minato Koichi , Seike Masahiro , Sasaki Shinichi , Kisohara Akira , Takeuchi Susumu , Honda Ryoichi , Takamura Kei , Ling Yiwei , Okuda Shujiro , Kagamu Hiroshi , Yoshimura Kenichi , Kikuchi Toshiaki , Kobayashi Kunihiko ,   North East Japan Study Group
Published: June 2023

9079 Background: EGFRm NSCLC patients (pts) have limited treatment options after EGFR-TKI failure. We previously showed that the NEJ043 study investigating ABCP in EGFRm NSCLC pts after EGFR-TKI failure had a clinically meaningful efficacy (Furuya et al, ASCO 2022). Here we report the results of the biomarker study of NEJ043. Methods: NEJ043 study is a phase II study to evaluate the efficacy of ABCP in sensitizing EGFRm nonsquamous NSCLC pts after TKI failure. Pts received atezo (1200 mg), bev (15 mg/kg), carbo (AUC 6 mg/mL/min), and pac (175 mg/m2) every 3 weeks up to 4 cycles followed by atezo plus bev until loss of clinical benefit. Before treatment initiation and three cycles of ABCP, peripheral blood mononuclear cells (PBMCs) were collected, and immunophenotypic data at each time point was obtained by flow cytometry. Results: 60 pts were included in the NEJ043 study and PBMCs were obtained from 31 pts. Pts with a higher percentage of CD11b+DRlowCD3-CD14+ myeloid-derived suppressor cells (MDSCs) before ABCP had significantly longer PFS (median, 9.7 months (95% CI, 5.3-17.7) vs 5.6 months (95% CI, 3.9-8.1); HR 0.38; P = 0.0313). Further analysis of the immune cell phenotypes that changed between pre-treatment and the third course showed that pts with increased CD62LlowCD8+ cells (median, 12.8 months (95% CI, 5.6-20.3) vs 5.7 months (95% CI, 4.4-8.1); HR 0.25; P = 0.003) and PD-1+CCR7-CD45RA-CD8+ cells (median, 8.5 months (95% CI, 5.6-13.8) vs 5.7 months (95% CI, 2.6-8.1); HR 0.37; P = 0.0324) had significantly longer PFS. Conclusions: Inhibition of MDSCs by ABCP, especially bev, may be important for EGFRm pts whose antitumor immunity is suppressed by MDSCs before treatment. Better PFS may be expected in pts in whom ABCP therapy induced CD62LlowCD8+ effector T cells and PD-1+CCR7-CD45RA-CD8+ effector memory T cells. Clinical trial information: jRCTs031190066 .
Tislelizumab plus chemotherapy in patients with advanced brain metastases of non-squamous non-small cell lung cancer: A multicenter, prospective, open-label phase 2 study.
Authors: Huang Yan , Yu Qitao , Yang Nong , Liu Li , Yu Yan , Wang Qiming , Zhao Yuanyuan , Yang Yunpeng , Jiang Wei , Tan Liping , Zhou Chunhua , Zeng Fanxu , Zhang Kai , Qin You , Zhang Shuai , Ma Shuxiang , Zhang Li 
Published: June 2023

9080 Background: Patients (pts) with brain metastases (BM) were usually unrepresented in clinical trials assessing the efficacy of PD-(L) 1 inhibitors. Here, we investigated the efficacy and safety of tislelizumab (TIS) plus chemotherapy in NSCLC pts with asymptomatic untreated BM or with stable BM after local radiotherapy. Methods: This multicenter, prospective, open-label phase 2 study enrolled systemic treatment-naïve pts with stage IV non-squamous (nsq) NSCLC without EGFR or ALK mutations who had BM. Pts received TIS combined with pemetrexed and carboplatin for 4 cycles, followed by maintenance TIS and pemetrexed. RECIST v1.1 and RANO-BM were applied for assessment for systematic and brain disease, respectively. The primary endpoint was the investigator-assessed 1-year PFS rate per RECIST v1.1. Results: 36 pts were enrolled with 77.8% having stage IVB disease, 25.0% liver metastases and 41.7% bone metastases. 29 (80.6%) pts were with untreated, asymptomatic brain metastases, and the other 7 (19.4%) received radiotherapy for BM previously. As of 30 Nov 2022, the median follow-up was 12.3 months. 1-year systematic PFS rate was 36.8% (95% CI, 18.0-55.7), with median PFS of 7.5 months (95% CI, 5.1-NE). Systematic ORR was 50.0% (95% CI, 31.9-68.1%). Median OS was not reached, with 1-year OS rate of 70.5% (95% CI, 51.7-83.1). For intracranial efficacy assessment per RANO-BM, 1-year intracranial PFS (iPFS) rate was 56.6 % (95% CI, 31.7-75.5), with 45.5% (95% CI, 19.4, 68.5) and 100% in pts with untreated and pretreated BM, respectively. Intracranial ORR was 56.7% (95% CI, 37.4-74.5%), with 53.8% (95% CI, 33.4-73.4%) in pts with untreated BM and 75% (95% CI, 19.4-99.4%) in pretreated BM. No grade 5 toxicities were observed. Grade 3-4 TRAEs occurred in 33.3% (12/36) of pts. 13.9% of pts experienced irAEs; grade 3-4 irAEs occurred in 2 (5.6%) pts. Conclusions: TIS plus chemotherapy yielded promising systematic and intracranial PFS, and was generally well tolerated in nsq-NSCLC pts with untreated or pretreated BM. Clinical trial information: NCT04507217 . [Table: see text]
Patient-reported outcomes of furmonertinib versus gefitinib in patients with locally advanced or metastatic, EGFR mutation-positive non-small cell lung cancer (FURLONG): A multicenter, double-blind, randomized phase 3 study.
Authors: Shi Yuankai , Chen Gongyan , Wang Xiang , Liu Yunpeng , Wu Lin , Hao Yanrong , Liu Chunling , Zhu Shuyang , Zhang Xiaodong , Li Yuping , Liu Jiwei , Cao Lejie , Cheng Ying , Zhao Hui , Zhang Shucai , Zang Ai-min , Cui Jiuwei , Feng Jian , Yang Nong , Hu Jie 
Published: June 2023

9081 Background: Furmonertinib showed superior efficacy compared with gefitinib as first-line therapy in Chinese patients with EGFR mutation-positive non-small cell lung cancer (NSCLC), along with an acceptable safety profile without new signals in the FURLONG study. Here we present patient-reported outcomes (PROs). Methods: FURLONG is a multicenter, double-blind, double dummy, randomized phase 3 study done in 55 hospitals across mainland China. Eligible patients were randomly assigned (1:1) to receive either furmonertinib or gefitinib. The primary endpoint of IRC-assessed progression-free survival has been reported previously. PROs as prespecified secondary outcomes by the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) and Quality-of-Life Questionnaire Lung Cancer 13 (QLQ-LC13), were analyzed in randomly assigned patients who had received at least one dose of study drug and completed at least one PRO assessment. Changes from baseline to randomized treatment discontinuation were analyzed with mixed model for repeated measures and time-to-event analyses. This study is ongoing for survival follow-up. Results: 357 patients received at least one dose of study drug, all of them completed at least one PRO assessment. Questionnaire completion rates were ≥95% at most time points. Baseline mean scores were similar in the furmonertinib and gefitinib groups. From baseline to randomized treatment discontinuation, statistically significant differences favoring furmonertinib for physical function, nausea/vomiting, appetite loss, diarrhea, alopecia, and other pain (any pain other than chest, arm, or shoulder pain) were observed. Time to deterioration in physical function, cognitive function, nausea/vomiting, appetite loss, diarrhea, cough, dyspnea, dysphagia, and alopecia were significantly longer with furmonertinib versus gefitinib (Table). Conclusions: Furmonertinib demonstrated favorable PROs as measured by the EORTC QLQ-C30 and QLQ-L13 versus gefitinib. These data presented the positive benefit risk profile of first-line furmonertinib and further support this novel third generation EGFR-TKI as a new standard of first line treatment in EGFR mutation-positive NSCLC. Clinical trial information: NCT03787992 . [Table: see text]
Mobocertinib efficacy in patients with NSCLC and EGFR exon 20 insertion mutations (ex20ins) identified by next-generation sequencing (NGS) of circulating tumor DNA (ctDNA).
Authors: Neal Joel W. , Li Ying , Yu Ziji , Fram Robert J. , Danes Christopher , Vincent Sylvie , Piotrowska Zofia 
Published: June 2023

9082 Background: EGFR ex20ins are distinct targetable driver mutations present in ~2% of all NSCLC. While most EGFR TKIs have limited effectiveness, mobocertinib is the first oral therapy approved for this unmet need. EGFR ex20ins are heterogeneous ( > 60 variants), and PCR testing detects a limited number of variants, leading to undetected disease in ~50% of cases, whereas NGS can identify all such mutations. Testing plasma ctDNA is a noninvasive approach for detection of genomic variants, such as EGFR ex20ins. Methods: In the mobocertinib phase 1/2 study (NCT02716116), patients were enrolled based on EGFR ex20ins detected by various local tissue or liquid clinical trial assays (CTAs). Baseline plasma samples were collected and processed to extract cell-free DNA and were evaluated for EGFR ex20ins status using FoundationOne Liquid CDX (F1LCDX), an NGS-based plasma ctDNA test. Concordance between F1LCDX and the CTAs was demonstrated by testing patient samples from the phase 1/2 trial and paired tissue and plasma samples from commercially acquired and stage-matched patients with NSCLC (N = 305). Efficacy analyses by assay method were performed in EGFR ex20ins–positive platinum-pretreated patients (PPP; n = 114 [FDA approved population]; data cutoff: 1 Nov 2021) in the phase 1/2 trial. Results: Concordance between F1LCDX and CTAs was demonstrated with samples from the CTA-positive (n = 159) and CTA-negative populations (n = 87) tested by F1LCDX where tissue and plasma were assessable; the point estimate of positive percentage agreement (95% CI) was 68.6% (61.0–75.3), and the point estimate of negative percentage agreement was 100% (95.8–100). F1LCDX detected 34 individual EGFR ex20ins variant types. In the response evaluable population, patients who tested EGFR ex20ins positive by F1LCDX (n = 55) demonstrated confirmed ORR (34.5%) and disease control rate (74.5%), which was comparable to those observed among all PPP in the phase 1/2 trial (confirmed ORR: 28%; confirmed disease control rate: 78%). Conclusions: Mobocertinib has shown efficacy in PPP with EGFR ex20ins NSCLC. F1LCDX effectively identified patients with EGFR ex20ins who may benefit from mobocertinib, providing an additional noninvasive diagnostic option to guide treatment. Clinical trial information: NCT02716116 .
Impact on turnaround times (TAT) among non-squamous non-small cell lung cancer (NSCLC) patients across three time periods with varying biomarker testing techniques.
Authors: Fan Zhen (Jason) , Tudor Roxana , Le Lisa W , Law Jennifer H. , Fung Andrea S. , Kuang Shelley , Meti Nicholas , Perdrizet Kirstin , Ranich Laura , Wei Cuihong , Sabatini Peter , Pal Prodipto , Tsao Ming Sound , Liu Geoffrey , Shepherd Frances A. , Bradbury Penelope Ann , Sacher Adrian G. , Eng Lawson , Cabanero Michael , Leighl Natasha B. 
Published: June 2023

9085 Background: Biomarker testing and identification of actionable genomic alterations (AGAs) in NSCLC patients have led to targeted therapy use and improved outcomes, particularly in advanced stages. We sought to evaluate the impact of different testing paradigms on TAT, particularly with respect to treatment decision and time to initiation of treatment, across three time periods. Methods: A retrospective review of stage III or IV non-squamous NSCLC patients at the Princess Margaret Cancer Centre (Toronto, Canada) was conducted. Both de novo advanced and patients with metastatic progressions are included. Cohort 1 (C1; 01/2015 – 01/2017) underwent reflex EGFR (EntroGen) and ALK (5A4 immunohistochemistry, IHC) single gene testing. Cohort 2 (C2; 02/2017 – 09/2020) underwent reflex next generation sequencing (NGS; Trusight Tumor 15), ALK and ROS1 testing. Cohort 3 (C3; 10/2020 – 01/2022) underwent reflex comprehensive NGS (161 genes, Oncomine OCA v3). Descriptive statistics are presented, including AGAs found and TAT from biopsy to result sign-out, and treatment related TAT. Results: Three cohorts of stage III and IV patients were identified, with C1 having proportionally more females (60%), never smokers (42%) with adenocarcinomas (98%). More patients with AGA were identified using NGS with larger panels (42%, 41%, 57%, respectively across C1 – C3). However, there is a longer median time from first oncology visit to treatment (14, 22, 27 days, respectively across C1-C3), and longer biopsy to treatment TAT trended towards more comprehensive testing (34, 38, 40 days, respectively across C1 - C3) in stage IV patients. Conclusions: As more comprehensive biomarker testing became available, more AGAs are identified with an increase in TAT from biopsy to sign-out and treatment start. Despite our institutional policy of reflex testing, future endeavours will be focus on ways to reduce TAT. [Table: see text]
Immune checkpoint inhibitors use and the incidence of hepatitis B virus reactivation or immune-related hepatitis in non-small cell lung cancer patients with chronic hepatitis B.
Authors: Hong Joohyun , Lee Jiyun , Park Sehhoon , Jung Hyun Ae , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Sinn Dong Hyun , Ahn Myung-Ju 
Published: June 2023

9086 Background: The safety and efficacy of immune-checkpoint inhibitors (ICIs) has not been thoroughly investigated in non-small cell lung cancer (NSCLC) patients with chronic hepatitis B (CHB) or occult hepatitis B infection (OBI). We analyzed incidence of hepatitis B virus (HBV) reactivation, immune-related hepatitis and jaundice in NSCLC patients treated with ICIs according to HBV DNA and hepatitis B serologic markers in real-world setting. Methods: A total of 1,277, consecutive NSCLC patients treated with ICIs from January 2015 to December 2020 at the Samsung Medical Center, Seoul, Korea were analyzed. Among them, 52 patients were hepatitis B surface antigen (+) (Group A, CHB), 759 patients were HBsAg (-)/anti-HBc IgG (+) (Group B, OBI), and 466 patients were HBsAg (-)/anti-HBc IgG (-) (Group C). Among 52 patients with CHB, 38 patients (73.1%) were receiving antiviral therapy. Primary endpoint was HBV reactivation, immune-related hepatitis and jaundice. Secondary endpoints include other immune-related adverse events, objective response rate, progression free survival (PFS) and overall survival (OS). Results: HBV reactivation was observed in two patients (0.2%) which was exclusively observed in Group A (CHB). Among CHB patients who were not receiving antiviral therapy, HBV reactivation was observed for 14.3% (2/14 patients). Incidence of immune-related hepatitis were 21.2%, 30.3% and 30.5% for Group A, Group B and Group C (p > 0.05), respectively, and incidence of immune-related of jaundice was 3.8%, 4.0% and 2.8% for Group A, Group B and Group C (p > 0.05), respectively. Incidence of ≥ grade 3 other immune-related adverse events, objective response rate, PFS, and OS were comparable among three group (p > 0.05 for all comparison). Conclusions: In this large, real-world cohort study, safety and efficacy of ICIs were comparable in patients with CHB or OBI, suggesting similar outcomes can be expected with ICIs in patients with CHB or OBI. HBV reactivation was observed in patients with CHB without antiviral therapy indicating antiviral prophylaxis might be required for them. For patients with OBI, risk of HBV reactivation was null.
First line (1L) durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2): Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.
Authors: Mark Michael Thomas , Froesch Patrizia , Gysel Katrin , Rothschild Sacha , Addeo Alfredo , Ackermann Christoph J. , Chiquet Sabrina , Schneider Martina , Ribi Karin , Fischer Maranta Angela , Bastian Sara , Von Moos Roger Anton Fredy , Joerger Markus , Früh Martin 
Published: June 2023

9088 Background: The safety and efficacy of 1L durvalumab in PS2 patients (pts) with advanced NSCLC is unknown. Important safety data leading to exclusion of pts with relevant respiratory symptoms have been published as an interim report. Here we present the primary analysis of 1L durvalumab in PS2 pts, unsuitable for combination chemotherapy and PD-L1 expression in ≥25% of tumor cells. Methods: In this single-arm, multicenter, phase II trial pts with PD-L1 positive (tumor proportional score, TPS ≥25%), advanced NSCLC with PS2, unsuitable for combination chemotherapy determined by the investigators, in the absence of known contraindications for immunotherapy and sufficient organ function, received a fixed dose of 1500 mg durvalumab every four weeks. The primary endpoint was overall survival (OS) at 6 months. The statistical hypothesis was to improve OS at 6 months from ≤35% to ≥53%. Adverse events (AEs) were assessed according to National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 5.0. Results: Forty-eight pts were included (29 males, 19 females). Median age was 76 years (range, 37-87). OS at 6 months was 60% (95% CI: 45-74%). OS at 6 months after the exclusion of pts with initially relevant respiratory symptoms was 67% (95% CI: 46-84%, n = 27) compared to the subgroup of pts without this exclusion criteria who were recruited before the amendment (52%, 95% CI: 30-74%, n = 21). Median OS was 8.5 months (95%CI: 4.4-16.7). Objective response rate and median PFS were 17% (95% CI: 8-30%) and 2.5 months (95% CI: 1.8-7.1). Thirty-three deaths (69%) were observed to date. Ten early fatal events considered not treatment-related occurred during the first 5 weeks of treatment. Four out of the first 7 early fatal events (4/7; 57%) were respiratory failures in pts with advanced symptomatic primary lung tumors. Only 3 more early fatal events occurred after the protocol amendment excluding pts with severe respiratory symptoms. Thirty-nine patients (81%) had an AE grade ≥3 (G3). The most frequent AEs ≥G3 were lung infection (19%), dyspnea (15%) and hypertension (10%), respectively. Treatment-related AEs ≥G3 were reported in 9 pts (19%) and included colonic perforation in one patient (grade 5), colitis in 5 pts (10%), hepatitis and increased lipase in 3 pts each (6%). Conclusions: 1L durvalumab in PS2 pts with advanced PD-L1 positive (TPS ≥25%) NSCLC is effective and led to a promising 6-month OS of 60%. Four-weekly durvalumab can be safely offered to pts presenting without severe pulmonary symptoms who are not candidates for chemotherapy. Clinical trial information: NCT03620669 .