bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lung cancer MDT quality assessment: A nationwide study.
Authors: Berg Janna , Aamelfot Christina , Aanes Siv-Gyda , Wilskow Marit , Bjaanæs Maria Moksnes , Brustugun Odd Terje , Fluge Sverre , Flåtten Per Andersen , Gronberg Bjorn Henning , Skraastad Terje , van Helvoirt Rene P , Petersen Martin , Tilseth Rune , Rasmussen Torben Riis , Neumann Kirill 
Published: June 2024

8594 Background: This observational study evaluates concordance between lung cancer multi-disciplinary team (MDT) meetings, focusing on diagnosis, staging, and treatment recommendations, especially for curative options. Assessing MDT decisions aims to identify factors potentially affecting survival rates, promoting equal treatment access for patients nationwide. Methods: In Norway, patients with lung cancer are discussed at local MDT (without a thoracic surgeon present) and at university hospital MDT (with a thoracic surgeon present). All hospitals received 35 fictitious case reports of patients with inoperable non-small cell (NSCLC) and small cell lung cancer (SCLC) with anonymized CT and PET images for discussion at the ordinary MDT meetings. Of the 12 participating hospitals, 5 were university hospitals. Results: Of the 35 patient’s cases, 12 were assessed as having stage III NSCLC. For 10 of the 12 there were differences in stage assessment, from stage IIIA-B-C to IV, and in recommended treatment (Table). For each case, curative treatment was recommended by a varying number of MDTs, from zero to nine of 12. Treatment suggestions for the four SCLC patients were identical except for one patient with stage IV, performance status (PS) score 2-3 and stroke, for whom the recommended treatment ranged from best supportive care (BSC) to triple therapy. There was generally good consensus between recommending treatment with a tyrosine kinase inhibitor (TKI) in patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) translocation positivity. We found that factors leading to discrepancies in MDT decisions were patients age >75-80 years, comorbidities, PS 2 or lack of a stated PS, PD-L1 more than 50-75% in stage IV and large cell neuroendocrine carcinoma (LNEC). Conclusions: MDT-recommendations regarding treatment varied between MDT sites, and this may have the greatest consequences for patients in stage III. MDT treatment recommendations varied between the sites, confirming that treatment choice can be challenging in certain type of cases like elderly, poor PS or LNEC. Shared decision-making (SDM) with patients was often recommended. As an important outcome of the study, we found no difference in treatment choice between local and university hospital MDTs. [Table: see text]
FDA analysis of immune checkpoint inhibitors in combination with vascular endothelial growth factor tyrosine kinase inhibitors in the second-line treatment of patients with advanced non-small cell lung cancer.
Authors: Malinou Justin Nathaniel , Mehta Gautam , Vellanki Paz J. , Larkins Erin A. , Kluetz Paul Gustav , Singh Harpreet 
Published: June 2024

8595 Background: Immune checkpoint inhibitors (ICIs) targeting PD-(L)1 in combination with platinum-based chemotherapy is standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC). The majority of these patients progress and there remains a high unmet medical need in the second-line setting given the limited FDA approved available therapies. The ICI plus vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI) combination, successful across several tumor types, was studied in NSCLC as a potential treatment option. Methods: The FDA identified 3 randomized trials conducted between June 2019 and August 2023, comparing the combination regimen ICI plus VEGF TKI to docetaxel in patients with advanced NSCLC who had progressed on both platinum-based chemotherapy and an ICI. All 3 trials were publicly reported to have not met their primary endpoint. Topline results for key efficacy and safety outcomes from each of the 3 trials were provided by the commercial sponsors. Results: 1317 total patients across 3 trials (LEAP-008, SAPPHIRE and CONTACT-01) were randomized to receive either an ICI plus VEGF TKI or docetaxel. The results are presented (Table). Efficacy parameters demonstrated similar results across trials between arms. There was no clear signal that the combination is more effective than single agent docetaxel. Safety parameters across trials consistently demonstrated higher rates of toxicity with the combination. Conclusions: ICI plus oral VEGF TKI combinations have not demonstrated an advantage over docetaxel in randomized trials of patients with advanced NSCLC. In 2 of the 3 trials, response rate data did not demonstrate superior efficacy compared to docetaxel. Additionally, any observed PFS benefit was small in magnitude. The relatively low efficacy, in combination with the additive toxicity of the regimen, may curtail a potential OS benefit. There remains a high unmet medical need in this patient population and further analysis is necessary to explore potential NSCLC subgroups which may derive benefit. [Table: see text]
Efficacy and safety of MCLA-129, an EGFR/c-MET bispecific antibody, in advanced non-small cell lung cancer (NSCLC).
Authors: Wang Jie , Zhong Jia , Wu Lin , Chen Bolin , Wang Zhe-Hai , Yao Yu , Dong Xiaorong , Li Wei , Ren Xiubao , Hou Xiaoming , Zang Ai-min , Qu Xiujuan , Zhang Guojun , Wang Yongsheng , Bai Yuansong , Liu Linlin , Yu Guohua , Chen Xingwu , Ding Lieming 
Published: June 2024

8604 Background: MCLA-129 is a common light chain, Biclonics, bispecific antibody targeting EGFR and c-MET with enhanced antibody-dependent cellular cytotoxicity. Here we describe the ongoing first-in-human phase 1/2 study of MCLA-129 in patients with NSCLC, including patients with MET exon 14 skipping (METex14) mutation (cohort A), EGFR exon 20 insertion (exon20ins)-mutated (cohort B) and sensitized EGFR-mutated disease (cohort C). Methods: Patients received MCLA-129 (100–2000 mg) IV biweekly or 1000-1500 mg IV weekly in a 28-day cycle in dose escalation. Doses at 1500 and 2000 mg IV biweekly are being explored in dose expansion. The primary endpoint was safety and tolerability. Objective response rate by investigator assessment per RECIST v1.1 of patients with NSCLC treated at 1500 and 2000 mg IV biweekly in three cohorts is reported. Results: As of 26 May 2023, 217 enrolled patients received MCLA-129 in China. The data cut-off was 24 Nov 2023. The most common treatment-emergent adverse events (TEAEs) were infusion related reaction (71.9%), hypoalbuminemia (54.8%), decreased neutrophil count (46.1%), and decreased white blood cell count (40.1%). TEAEs mostly were grade 1-2. Grade ≥3 TEAEs and drug-related TEAEs were reported in 51.6% and 39.2% of patients, respectively. 176 of the 215 NSCLC patients were evaluable. The confirmed objective response rates (ORR) in Cohort A, B and C were 43.5%, 28.6% and 21.8%, respectively. Especially, for patients in Cohort A receive prior MET TKI, the ORR was 37.5% and disease control rate (DCR) was 93.8%. Overall efficacy is shown (Table). Conclusions: MCLA-129 demonstrates robust and durable antitumor activity in patients with NSCLC harboring METex14, EGFR exon20ins and sensitized EGFR mutations, with a manageable safety profile; enrollment in dose expansion is ongoing. Clinical trial information: NCT04930432 . [Table: see text]
Final analysis of SCARLET study: A single-arm, phase II study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer KRAS G12C mutation.
Authors: Yoshioka Hiroshige , Akamatsu Hiroaki , Sakata Shinya , Azuma Koichi , Uemura Takehiro , Tsuchiya-Kawano Yuko , Osuga Mitsuo , Koh Yasuhiro , Morita Satoshi , Yamamoto Nobuyuki 
Published: June 2024

8616 Background: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Methods: Efficacy and safety of sotorasib in combination with platinum-doublet chemotherapy in KRAS G12C-mutated non-squamous, non-small cell lung cancer (non-Sq, NSCLC) has been reported with a limited follow-up period. Results: Between Oct 2021 and Jul 2022, 30 patients were enrolled and the median follow-up time was 14.8 months (range, 0.6-21.7). The primary endpoint, ORR by independent review was 88.9% (80%CI 78.5-94.8%, 95%CI 70.8-97.6%). Median PFS was 6.6 months (95%CI 5.3-16.7 months) and PFS rate at 12 months was 37.0%. Median time to treatment failure was 7.9 months (95%CI 5.4-13.9 months). Median OS was 20.6 months (95%CI 8.1 moths - not estimated) and OS rate at 12 months was 66.7%. Similar to the initial report, efficacy did not differ by PD-L1 expression level. In patients with PD-L1 expression level ≥50% / 1-49% / < 1%, ORR was 76.9% / 100.0% / 100.0%, and median PFS was 7.6 / 5.7 / 9.7 months, respectively. Common adverse events were anemia, platelet count decreased, neutrophil count decreased, decreased appetite and nausea. Grade≥3 AEs were mostly hematological toxicities, and one treatment-related death (pneumonia) occurred. Twenty-two plasma samples were collected and analyzed using NGS at the time of disease progression. Of those, an increased allele frequency of KRAS G12C was observed in 73% of the patients. TP53 mutation was detected in 55%, and other resistance mechanisms included CDKN2A, BRAF and PIK3CA mutations. Conclusions: Sotorasib in combination with CBDCA/PEM demonstrated favorable ORR with modest PFS and good tolerability in advanced non-Sq, NSCLC patients with KRAS G12C mutation. Clinical trial information: jRCT2051210086 .
Efficacy of immunotherapy retreatment in patients with non-small cell lung cancer receiving consolidative durvalumab.
Authors: Carroll Allison Baker , Kohler Lindsay Renee , Cipriani Amber Britton , Patel Shetal Arvind , Chen Kevin Yanjun 
Published: June 2024

8625 Background: The standard of care for patients with stage III, unresectable non-small cell lung cancer (NSCLC) is curative intent chemoradiation followed by durvalumab consolidation. However, most patients progress necessitating further treatment. Although immunotherapy (IO) is the cornerstone of treatment in advanced/metastatic disease, the benefit in patients who received prior durvalumab is unclear. Clinical trials excluded prior IO exposure and current guidelines do not provide specific recommendations. This study aims to characterize the efficacy of post-durvalumab IO treatment. Methods: This was a retrospective cohort study conducted at the University of North Carolina (UNC) Medical Center. Adult patients with unresectable NSCLC who received chemoradiation and consolidative durvalumab followed by subsequent systemic therapy for disease progression between February 2018 to May 2023 were included. Patients were excluded if they received targeted therapy as subsequent systemic treatment. The primary endpoint was real-world progression-free survival (rwPFS) of post-durvalumab treatment. Key secondary outcomes included physician assessed response, overall survival (OS), and subgroup analyses to identify biomarkers which may predict benefit from IO retreatment. Results: A total of 66 patients met inclusion criteria, of which 39 (59%) received subsequent chemotherapy alone and 27 (41%) received IO-containing therapy. Of those who received IO-containing treatments, 18 received chemotherapy plus IO (chemoIO) and 9 received IO alone. Durvalumab was discontinued for therapy completion (chemotherapy: 18%, IO: 26%), disease progression (chemotherapy: 54%, IO: 48%), or side effects (chemotherapy: 26%, IO: 19%). No significant difference was observed between median rwPFS of chemotherapy versus IO-containing therapy (7.0 months vs 5.8 months, respectively; p = 0.9419) or OS (13.0 months vs 12.6 months, respectively; p = 0.5769). Notably, patients in our cohort who received IO alone had a numerically longer rwPFS compared to chemoIO (12.6 months vs 5.8 months, respectively; p = 0.3951), as well as a numerically longer OS (12.6 months vs 6.4 months, respectively; p = 0.8885). Conclusions: This study found that there were no statistically significant differences in median rwPFS or OS between chemotherapy or IO-based regimens following the conclusion of durvalumab consolidation. Interestingly, we observed a numerically improved rwPFS and OS in those who received IO alone compared to chemoIO, which suggests there may be key clinical or molecular features that may help identify patients who benefit from IO therapy. We acknowledge the limitations of this small, retrospective study. The efficacy of IO-based regimens post-durvalumab warrants further investigation in a larger, prospective manner to assess the risks and benefits of IO retreatment.
High PD-L1 expression among patients with ALK rearranged non–small cell lung cancer and response to first line ALK tyrosine kinase inhibitors.
Authors: Nie Yunan , Staley Alyse , Hinz Trista , Merrick Dan , Yang Michael , Schenk Erin L. , Bunn Paul A. , Camidge David Ross , Heasley Lynn , Patil Tejas 
Published: June 2024

8626 Background: Patients with ALK rearrangements are highly responsive to ALK tyrosine kinase inhibitors (TKIs). Negative prognostic markers to ALK TKIs include TP53 alterations and ALK Variants 3a/b. The prognostic role that PD-L1 expression plays in first line ALK TKI outcomes is less clear. Methods: Retrospective review of patients with metastatic ALK-rearranged NSCLC seen between 2015 - 2022 at the University of Colorado who received first line ALK TKIs was performed. PD-L1 expression was denoted as high (≥50%) or low (< 1% or 1-49%) based on pre-treatment biopsies. Clinicopathologic features, treatment outcomes, and genomic data were collected. Survival outcomes were assessed using Kaplan Meier methods. Multivariate modeling adjusted for brain metastases, TP53 mutations, ALK variant status, and ALK TKI. PD-L1 was overexpressed in EML4-ALK murine cell lines with lentiviruses. In vitro and in vivo response to ALK TKIs were compared to non-infected cell lines. Neutrophils and lymphocytes were quantified on pre-treatment H&E slides. Results: Baseline characteristics of 130 patients are shown. Median PFS was significantly (p < 0.001) longer in the PD-L1 low cohort than the PD-L1 high cohort (21 vs 11 mos, HR 0.44, 95% CI 0.29 – 0.66). There was no difference in OS between the PD-L1 low and PD-L1 high cohort (p = 0.4, 107 vs 91 mos, HR 0.86, 95% CI 0.46 – 1.61). In an alectinib sub-group analysis (n = 89), PD-L1 high expressers had a higher rate of CNS progression (93.0 vs 73.9%, p = 0.022). Forced overexpression of PD-L1 in murine EML4-ALK cell lines exerted no difference to in vitroor in vivo response to alectinib. Pre-treatment biopsies from the PD-L1 high cohort (n = 19) revealed significantly more neutrophils (p = 0.021), but not lymphocytes (p = 0.904). Conclusions: High PD-L1 expression (≥50%) is associated with worse PFS and higher intracranial progression rate among those receiving ALK TKIs. Induced PD-L1 expression in ALK cell lines did not alter in vitro or in vivo ALK TKI sensitivity. Higher neutrophil counts track with high PD-L1 expression (≥50%), suggesting that differences within the immune tumor microenvironment may be relevant. [Table: see text]
Clinical-genomic characteristics in patients with EGFR-mutated non-small cell lung cancer harboring MET copy number gains after progression on EGFR-TKI: A report from LC-SCRUM-TRY.
Authors: Hirata Tsuyoshi , Izumi Hiroki , Matsumoto Shingo , Nishino Kazumi , Kato Terufumi , Kodani Masahiro , Chikamori Kenichi , Hosomi Yukio , Hara Satoshi , Kawashima Yosuke , Kuyama Shoichi , Shibata Yuji , Udagawa Hibiki , Sakai Tetsuya , Sugiyama Eri , Nosaki Kaname , Zenke Yoshitaka , Umemura Shigeki , Yoh Kiyotaka , Goto Koichi 
Published: June 2024

8628 Background: MET amplification (amp) account for 10-15% of resistance mechanism in EGFR-mutated non-small cell lung cancer (NSCLC) to EGFR-tyrosine kinase inhibitor (TKI) treatment. MET copy number (CN) gains consists of MET focal amp and polysomy (poly), but the clinical characteristics and outcome of EGFR-TKI resistant NSCLC patients harboring MET amp, poly remains unclear. Methods: The clinical-genomic characteristics and treatment outcome ofEGFR-TKI resistant EGFR-mutated NSCLC registered in LC-SCRUM-TRY (UMIN000041957) were analyzed. Genetic resistant alterations were screened using next-generation sequencing (NGS) (Tissue; Oncomine Precision Assay [OPA] or Plasma; Guardant360 [G360]), and MET-fluorescence in-situ hybridization (FISH). MET amp was defined as MET CN ≥4 (OPA), MET CN ≥2.12 (G360) or MET/CEP7 ratio ≥2 (FISH). MET poly was defined as MET CN≥5 and MET/CEP7 ratio <2 by FISH. Results: A total of 1559 patients had been enrolled in LC-SCRUM-TRY between Sep 2020 and Jan 2024. Of 1537 analyzed samples, 666 (43%) were EGFR-TKI resistant samples. Of these, 92 (14%), 239 (36%) and 335 (50%) had MET amp, poly, and no CN gain (no CNG), respectively. Patient characteristics and treatment outcome with 1st line EGFR-TKI and platinum-based chemotherapy (PBC) post EGFR-TKI is summarized (Table 1). The overall response rate (ORR) of PBC post EGFR-TKI in the patients with MET amp, poly and no CNG was 41%, 29% and 31%, respectively (p=0.34), with median progression-free survival (mPFS) being 5.7 months, 6.8 months, and 6.7 months (p=0.02). In addition, 12 and 11 of patients with MET amp and poly were enrolled into clinical trial of MET-targeted therapy (MET-TKI, n=2; MET-antibody-drug conjugate [ADC], n=4; EGFR/MET-antibody, n=2), and MET non-targeted therapy (EGFR-TKI, n=5; other ADCs, n=10: immunotherapy; n=1). The ORR of MET-targeted therapy/MET non-targeted therapy were 60/0% for MET amp, and 0/33% for MET poly, respectively. Conclusions: Patients with shorter PFS with prior 1st line EGFR-TKI are more likely to have MET amp. The efficacy of standard PBC post EGFR-TKI in patients with MET CNG is limited. Current MET-targeted therapy may not be effective for EGFR-mutated NSCLC harboring MET poly after progression on EGFR-TKI. [Table: see text]
Preliminary results from a FIH, open-label phase 1 study with BMC128, a rationally designed live bacterial consortium, in combination with nivolumab.
Authors: Perets Ruth , Meshner Shiri , Tirosh Osnat , Eshar Shiri , Metz-Breiner Alona , Kruger Ben-Shabat Sheerli , Ben-Yehuda Hila , Haber Elran , Cohen-Asis Meital , Maurice-Dror Corinne , Ringel Yehuda , Holland Roy , Shirman Yelena , Shentzer kutiel Talia 
Published: June 2024

8631 Background: Immune-Checkpoint inhibitors (ICI) have transformed the treatment of solid tumors, specifically in cutaneous melanoma, clear cell renal cell carcinoma (ccRCC) and non-small cell lung cancer (NSCLC). Despite these advances, resistance to ICI eventually occurs in many patients. Recent reports have found that patients showing poor response to ICI are characterized by a reduced gut microbiome diversity, suggesting that the gut microbiome might affect immune activation by ICI. BMC128 is a live bacterial consortium of 4 bacterial strains designed to induce anti-tumor immune function when given in conjunction with ICI. These strains were identified by analyzing microbiome data obtained from NSCLC and ccRCC patients presenting varied responses to ICI, using a proprietary computational discovery platform enabling high-resolution functional microbiome analysis. In pre-clinical studies, treatment with BMC128 potentiated the efficacy of ICI in breast cancer and melanoma mouse models, reducing tumor volume, increasing the number of responders, and demonstrating an increase in infiltrating immunocytes: CD4, CD8 and NK cells. The aim of this study was to assess the safety and tolerability of BMC128 in combination with nivolumab. Methods: 12 patients with ccRCC, cutaneous melanoma and NSCLC-adenocarcinoma (EGFR/ALK wild-type) (6, 1 and 5 patients, respectively), who previously progressed on PD1/PDL-1 inhibitors were recruited to this FIH open label phase 1 study. Patients were treated with a daily oral dose of BMC128 4*108 live cells/ strain in combination with nivolumab 480mg q4weeks. The study treatment consisted of 4 stages: depletion with antibiotics, induction with BMC128 monotherapy, combination treatment, and nivolumab monotherapy. Results: No SAEs related to BMC128 were reported throughout the duration of the study. Two patients exhibited minor AEs that were potentially associated with BMC128. At the current time point, 4 out ofthe first 8 patients in the study showed SD and sustained benefit beyond the first imaging timepoint, following the combination treatment. Altogether demonstrating clinical benefit for a total of 16 weeks (2 patients), 24 weeks (1 patient), and 68 weeks (1 patient). Conclusions: BMC128 has demonstrated an excellent safety profile and preliminary beneficial clinical effect. A phase 2 study to investigate the efficacy of BMC128 is planned to be initiated in late 2024. Clinical trial information: NCT05354102 .
Safety and efficacy of osimertinib in patients with NSCLC and uncommon tumoral EGFR mutations: A systematic review and meta-analysis.
Authors: N. Priantti Jonathan , Vilbert Maysa , Moraes Francisco Cezar A , Michelon Isabella , Castro Caio , Leighl Natasha B. , Cavalcante Ludimila , Fujiwara Yu , Addeo Alfredo , Bar Jair , Cortellini Alessio , Nassar Amin , Naqash Abdul Rafeh 
Published: June 2024

8642 Background: Osimertinib is broadly used for advanced EGFR-mutant NSCLC patients. However, the activity of osimertinib is not fully characterized in tumors harboring uncommon EGFR mutations, which represents about 10% of EGFR-mutated NSCLC cases. Hence, we conducted a systematic review and meta-analysis to assess the efficacy and safety of osimertinib in patients with NSCLC and uncommon tumoral EGFR mutations. Methods: PubMed, Embase, and the Cochrane Library were searched for eligible studies. Uncommon EGFR mutations were defined as any mutation other than the exon 19 deletion, L858R and T790M mutations, and exon 20 insertion, except when in compound. Efficacy was assessed by objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Heterogeneity was examined with I2 statistics and random-effect model was used for a meta-analysis. Results: Nine studies comprising 331 patients were included. Median follow-up ranged from 12.6 to 22.0 months (mos). Median age in each study ranged from 51 to 72 years old (table). Overall, 62% (205/331) of patients were female and 77% (256/331) of patients had an ECOG PS ≤1. About 78% (258/331) of patients received Osimertinib in a 1st line setting. Uncommon tumoral EGFR mutations included G719X in 40% (131/331) of patients, L861X in 27% (91/331), and S768I in 15% (49/331). Pooled analysis showed an overall ORR of 49.5% (95% CI, 42.2 – 56.9), a DCR of 90.2% (95% CI, 86.2 – 94.3), a median OS of 24.5 mos (95% CI, 11.9 – 24.5), a median PFS of 9.5 mos (95% CI, 8.2 – 11.0), and a median DOR of 17.4 mos (95% CI, 7.9 – 22.7). Intracranial (i) efficacy had an iORR of 50.3% (95% CI, 30.3 – 70.3), an iDCR of 92.8% (95% CI, 76.2 – 100), and a median iPFS of 6.1 mos (95% CI, 4.5 – 6.6). In a subgroup analysis according to EGFR mutation, overall ORR was significantly different in patients with tumoral G719X, S768I and L861 mutations (ORRs of 28.8%, 33.3%, and 67.7%, respectively, p for subgroup differences < 0.01). Overall, osimertinib was well tolerated with a frequency of all-grade AEs of 86.2% (95% CI, 61.2 – 100) and ≥ G3 of 18.0% (95% CI, 1.2 – 34.7). Conclusions: This systematic review and meta-analysis suggests that patients with NSCLC with uncommon tumoral EGFR mutations may benefit from osimertinib treatment. Patients harboring tumoral L861 mutation achieved a significantly higher ORR compared to the modest ORR in G719X, S768I cases. [Table: see text]