bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of durvalumab in patients with unresectable stage 3 non–small cell lung cancer post-chemoradiotherapy.
Authors: Thurlapati Aswani , Dhaliwal Lovekirat Singh , Chennapragada Sumasri , Gutta Pranavteja , Song Diana , Ralla Deepika , Comeau Jill , Shi Runhua , Beedupalli Kavitha 
Published: June 2022

8550 Background: The PACIFIC study (PS) concluded that the use of durvalumab from 1 to 42 days after concurrent chemoradiotherapy (CXRT) in stage 3 unresectable non-small cell lung cancer (NSCLC) increased the median overall survival (mOS) from 29 to 48 months. It also showed a benefit in tumors with PD-L1 <25%. However, a post-hoc analysis of the PS showed no survival benefit with durvalumab in patients with PD-L1 <1% but was not statistically powered. Currently in the US, durvalumab is approved irrespective of PDL-1 percentage, whereas in Europe it is not approved for tumors with PDL-1 <1%. Also, there was no survival benefit in starting durvalumab within and after 2 weeks of CXRT. Our objectives in this study are to analyze the impact of PDL-1 expression and the date of initiation of durvalumab post CXRT on mOS. Methods: We conducted a retrospective observational study of stage 3 unresectable NSCLC patients who received durvalumab post CXRT at LSU Health Shreveport from 2018 to 2021. A survival analysis was done including the following variables: age, race, sex, tumor histology, tumor PD-L1 percentage, and date of initiation of durvalumab post CXRT. P-value <0.05 was considered statistically significant. Results: We identified 83 patients who received durvalumab after CXRT for treatment of stage 3 unresectable NSCLC. Baseline characteristics are provided in table 1. Among all the tumors, 25% had a PDL-1 <1%. 33% of the study population received durvalumab less than 30 days after CXRT and 67% received it after 30 days. The mOS was not impacted by race, sex, or tumor hisotology. Compared to higher PDL-1 percentage, patients with PD-L1 <1% had a statistically significant lower survival probability. At 14 months, 87% of patients with a PD-L1 <1% were alive compared to 100% in those with a PD-L1 1-50% or a PD-L1 >50%. Less than 35% of patients with PD-L1 <1% survived beyond 30 months compared to 45% for PD-L1 1-50% and 100% for PD-L1 >50% (p-value 0.02). Patients who received durvalumab 30-60 days after concurrent CXRT had a lower OS at 30 months compared to those who started before 30 days (44% versus 90%). However, statistical significance was not reached (p-value 0.45). Conclusions: This study demonstrates that patients with a PD-L1 tumor expression of <1% had a statistically significant lower survival probability compared to those with a PD-L1 expression of 1-50% and > 50% in this patient population. Time from CXRT to the start of durvalumab was not shown to affect survival outcomes.[Table: see text]
Nab-PTX and nab-PTX combined with immune checkpoint inhibitors for relapsed small cell lung cancer.
Authors: Wan Rui , Wang Jie , Duan Jianchun , Wang Zhijie 
Published: June 2022

8576 Background: Despite sensitivity to first-line chemotherapy, most small cell lung cancer (SCLC) patients experience disease progression after initial treatment. Nab-PTX showed comparable anti-tumor activity for relapsed SCLC. Whether immune checkpoint inhibitors (ICIs) combined with nab-PTX could improve clinical outcome for relapsed SCLC has not been fully evaluated. The aim of this study is to evaluate efficacy and safety of nab-PTX and nab-PTX combined with ICIs for relapsed SCLC. Methods: We retrospectively reviewed relapsed SCLC patients who were given nab-PTX (130mg/m2, day1,8 /Q3 weeks) or nab-PTX combined with ICIs (PD-1 or PD-L1), from Feb 2017 to Sep 2021. Clinical data were collected from electronic medical records. The clinical outcome, including progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan-Meier method and standard Log-rank test. Results: A total of 56 patients with relapsed SCLC were included, 29 and 27 patients received nab-PTX (group A) and nab-PTX combined with ICIs (group B), respectively. Baseline characteristics were well balanced between the groups. Patient characteristics (group A: group B) were as follows; median age 57: 59, male 25(86.2%): 24(88.9%), heavy smoking 23(79.3%): 18(66.7%), ECOG-PS 1 19(65.5%) :19(70.4%), extensive disease 28(96.6%) :25(92.6%), liver metastasis 10(34.5%) :12(44.4%), brain metastasis 8(27.6%) :10(37%), refractory relapse 10(34.5%) :11(40.7%). ORR in group A and B were 17.2% vs 40.7%, and DCR in group A and B were 72.4% vs 66.7%, respectively. The median PFS and median OS were similar between group A and B (median PFS, 2.8months vs 3.2months; median OS, 9.3 months vs 11.0months). PFS and OS according baseline characteristics were showed in the table. Toxicity profile of group B was tolerable as well as group A. Conclusions: This retrospective study indicated nab-PTX combined with ICIs failure to improve clinical outcome for relapsed SCLC when compared with nab-PTX monotherapy.[Table: see text]
Efficacy and safety of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer: Preliminary results of a phase 1 study.
Authors: Cheng Ying , Wu Chunjiao , Chen Lulu , Xin Ying , Zhang Liang , PAN Pinghua , Wu Lin , Li Juan , Zhao Yanqiu , Li Xingya , Zhao Jun , Dong Xiaorong 
Published: June 2022

8580 Background: Lurbinectedin (Zepzelca), a selective inhibitor of oncogenic transcription, was granted accelerated approval on June 15, 2020, by the FDA for adult patients (pts) with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy, based on the results from SCLC cohort in PM1183-B-005-14 trial. Here we report the preliminary results of a phase 1 study (LY01017/CT-CHN-101) which aimed to evaluate the safety, tolerability, pharmacokinetics (PK) characters and preliminary efficacy of lurbinectedin in Chinese pts with advanced solid tumors including relapsed SCLC. Methods: In the dose-escalation stage, 10 pts with advanced solid tumors received lurbinectedin (2.5-3.2 mg/m2) as 1-hour i.v. infusion q3wk in a classical 3+3 design, without primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during Cycle 1. In the dose-expansion stage, 22 pts with relapsed SCLC after first-line platinum-based chemotherapy were treated with single-agent lurbinectedin at the recommended dose (RD) defined in the dose-escalation stage, with or without G-CSF support. Endpoints included safety (CTCAE v5.0), tolerability, PK, and confirmed objective response rate (ORR; RECIST v1.1). The data cutoff was January 13, 2022. Results: No dose-limiting toxicity (DLT) was observed in the first 3 pts treated at 2.5 mg/m2, while 1/7 pts treated at 3.2 mg/m2 had DLT (grade 4 neutropenia lasting ≥3 days) in Cycle 1, thus 3.2mg/m2 without G-CSF prophylaxis was defined as the RD of the dose-expansion stage. At cutoff, 22 SCLC pts treated in the dose-expansion stage were still ongoing, with 21 and 22 pts evaluable for efficacy and safety, respectively. The investigator-assessed confirmed ORR was 42.9% (9/21, partial responses). The duration of response (DOR) is pending. The most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (16 [72.7%]), leukopenia (13 [59.1%]), thrombocytopenia (9 [40.9%]), increased ALT (4 [18.2%]), anemia (3 [13.6%]), and increased AST (2 [9.1%]). Serious treatment-related adverse events, including neutropenia (5 [22.7%]), leukopenia (4 [18.2%]), thrombocytopenia (3 [13.6%]), increased ALT (2 [9.1%]), increased AST (2 [9.1%]), vomiting (2 [9.1%]), febrile neutropenia (1 [4.5%]), and edema (1 [4.5%]), were reported in 10 pts (45.5%). No cases of infection, sepsis and Hy’s law were reported. A total of 40.9% (9/22) had dose delay and 31.8% (7/22) had dose reduction, mainly attributed to hematological toxicities. No discontinuations occurred due to AEs. No treatment-related deaths were reported. Conclusions: Lurbinectedin at the RD (3.2mg/m2) shows promising efficacy as second-line therapy in Chinese pts with SCLC, with acceptable tolerability and manageable safety profile. Clinical trial information: NCT04638491.
Trends in treatment patterns associated with small cell lung cancer in a U.S. Medicare population.
Authors: Ramirez Robert A. , Boyd Marley , Cockrum Paul 
Published: June 2022

8584 Background: Characterizing changes in the incident small cell lung cancer (SCLC) patient population and SCLC treatment landscape is essential for understanding drivers of outcomes among patients diagnosed with SCLC. The objective of this study was to examine trends in patient characteristics and treatment patterns for SCLC in a Medicare population. Methods: A retrospective analysis was conducted using the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked data. Patients were included if they had a record with a diagnosis of SCLC in the database from 1/1/2007 – 12/31/2017 and were ≥65 years of age at diagnosis. Patients also had continuous enrollment for ≥180 days pre-SCLC diagnosis. Characteristics and treatment patterns were stratified by year of SCLC diagnosis. Results: 13,516 patients met the study criteria. Overall, 57.7% were female, mean age was 74 years, 89.5% were white, and 45.6% had a history of tobacco use. The majority (73.1%) were diagnosed with stage IV disease. Just over half (55.4%) of patients initiated first line (1L) treatment and mean time from diagnosis to 1L treatment was 6 weeks. Only 36.7% of those initiating 1L went on to second line (2L). Platinum-based chemotherapy (carboplatin or cisplatin + etoposide) was by far the most common 1L regimen (91.3%). 44.7% of patients received monotherapy in 2L, with topotecan being the most common (28.4%) regimen. Carboplatin + etoposide was used for approximately 20% of 2L patients. Over time, the demographic characteristics of patients diagnosed with SCLC was fairly stable with the exception of patients reporting a history of tobacco use, which more than tripled, increasing from 19.3% to 67.7% between 2007 and 2017. Between 2007 and 2017 the share of SCLC patients initiating 1L treatment increased 8.2% from 53.8% to 58.2% and the share initiating 2L fluctuated between 35% and 39%. Platinum-based chemotherapy was consistently used by the vast majority (88.7%–96.6%) of patients in 1L during the study period. Other chemo monotherapy (e.g., topotecan) and platinum-based chemotherapy with or without irinotecan were the most common 2L regimens from 2007-2014. Use of checkpoint inhibitors (CPIs) in 2L began in 2015 and became the most common 2L treatment following platinum-based chemotherapy by 2017 with 41.5% of patients receiving a CPI in 2L. Conclusions: While an increasing share of SCLC patients are pursuing treatment, less than 60% of SCLC patients receive any anticancer therapy. Fewer still receive more than one line of treatment, highlighting the ongoing need for effective therapies for SCLC.
Impaired seroconversion after SARS-COV-2 mRNA vaccine in patients with thymic epithelial tumors.
Authors: Pietroluongo Erica , De Placido Pietro , Morra Rocco , Ottaviano Margaret , Tortora Marianna , Saponaro Mariarosaria , Pisapia Luca , Del Gaudio Giancarlo , Del Deo Vitantonio , Malfitano Anna Maria , Cernera Gustavo , De Angelis Carmine , Arpino Grazia , Terracciano Daniela , Castaldo Giuseppe , Formisano Pietro , Palmieri Giovannella , De Placido Sabino , Giuliano Mario 
Published: June 2022

8588 Background: Thymic epithelial tumors (TET) are rare malignancies associated with dysregulation of the immune system and humoral and cell mediated immunity abnormalities. Anti-syndrome coronavirus type 2 (SARS-CoV-2) vaccine is effective at preventing COVID-19 morbidity and mortality. No published data are available regarding the immunization in TET patients (pts). The aim of this study was to evaluate the immunization in TET pts who received two doses of mRNA vaccine, by longitudinal serological detection of SARS-COV-2 spike-binding IgG antibody. Methods: Starting from April 2021 to October 2021, consecutive TET pts referred to the Rare Tumors Coordinating Center of Campania Region (CRCTR - Naples, Italy) were enrolled. All study subjects received two doses of COVID-19 mRNA vaccine (BNT162b2 by Pfizer-BioNTech). SARS-CoV-2 spike-binding IgG antibody (Ab) serological levels were analyzed by centralized chemiluminescent immunoassay (CLIA) at different time-points, including before 1st vaccine dose (T0) and 1 month after 2nd dose (T2). Cut-off for Ab titers positivity was > 25 AU/mL. Results: Forty pts were enrolled; 23 (57.5%) were female and 17 (42.5%) male. Eleven pts (27.5%) suffered from thymic carcinoma, 28 (70%) thymoma, and 1 (2.5%) thymic hyperplasia. At the time of study enrollment, 20 pts (50%) had no evidence of disease (NED) and were in follow-up; the remaining 20 pts had evidence of disease (ED) by imaging and were receiving systemic treatment (55% oral low-dose etoposide-based therapy, 40% somatostatin analogs + prednisone, 5% supportive care). Immune system disorders were diagnosed in 29 TET pts (72.5%): 19 pts (47.5%) had Good’s Syndrome (GS) and 10 (25%) other immune disorders. At T0, all enrolled pts had negative Ab titers and no prior SARS-CoV-2 infection. At T2, Ab data were available for 37 pts (92.5%): 18 pts (48.7%) had positive Ab titers, whereas 19 (51.3%) did not achieve seroconversion. Among pts with ED, seroconversion was achieved only in 2 cases (11.8%). Lack of seroconversion at T2 was significantly associated with ED (Fisher's exact test p: 0.0001) and with the presence of GS (Fisher's exact test p: 0.0489). No significant association of seroconversion with other immune disorders and disease features was found. Conclusions: Our data showed that TET pts with ED had substantially higher probability of impaired seroconversion after SARS-COV-2 vaccine as compared with NED pts. We warrant further studies to evaluate the role of disease status, anti-tumor treatments and immune disorders in post-vaccine immunization of TET pts.
Platinum-free chemotherapy in the new era of immunotherapy: A phase II study of camrelizumab combined with apatinib and albumin paclitaxel in advanced non-squamous NSCLC (CAPAP-lung).
Authors: Wu Lin , Pu Xingxiang , Lin Gen , Xiao Maoliang , Lin Jie , Wang Qianzhi , Kong Yi , Yan Xuejun , Xu Fang , Xu Yan , Li Jia , Li Kang , chen bolin , Wen Xiaoping , Tan Yali 
Published: June 2022

9034 Background: Cytotoxic chemotherapy and anti-angiogenic therapy may enhance the therapeutic efficacy of immune checkpoint inhibitors (ICIs). Platinum-containing dual-agent chemotherapy combined with ICIs is the standard first-line treatment for non-small cell lung cancer (NSCLC), however, the optimal combination regimen remains unclear. The adverse effects of platinum-based chemotherapy are relatively serious, whether platinum chemotherapy can be eliminated in the first-line treatment of non-small cell lung cancer is a hotspot and difficulty in current research. Based on these results, we initiated CAPAP-lung study, which is a single-arm, multicenter Phase II trial to evaluate the efficacy and safety of Camrelizumab in combination with apatinib and albumin paclitaxel without platinum as the first-line therapy for non-squamous non-small cell lung cancer. Methods: Patients diagnosed with ⅢB-IV non-squamous NSCLC without EGFR and ALK sensitive mutations received Camrelizumab (200mg/3w) in combination with Albumin Paclitacxel (135mg/m2, d1, d8/3w, 4-6 cycles) and Apatinib (250mg Qd po for 5 days, resting for 2 days every week). From August 2020 to February 2022, 54 of the planned 63 patients have been enrolled. The primary endpoint is progression-free survival(PFS), and secondary endpoints were overall survival (OS), duration of Response (DOR), objective response rate (ORR), and disease control rate (DCR) assessed by RECIST v1.1. This study is registered with ClinicalTrials.gov, NCT04459078 (follow-up is ongoing). Results: The data for a total of 38 patients out of 54 enrolled patients were evaluable. Median PFS was 10.97 mo (95%CI 7.1-NR).The objective response rate (ORR) and disease control rate (DCR) were 71.1% (27/38, 95%CI 53.9-84.0) and 97.4% (37/38, 95%CI 84.6-99.9), respectively. The incidence of grade 3 and worse treatment-related adverse events was acceptable, with grade 3 events in 25(46.3%) patients and grade 4 events in 3(5.6%) patients. The most common grade 3 treatment-related adverse events were decreased neutrophil count (8 [14.8%]), liver function damage (9 [16.7%]), rash (3 [5.6%]), and decreased white blood cell count (3 [5.6%]). Conclusions: Camrelizumab combined with albumin paclitaxel and apatinib showed encouraging antitumor activity with an acceptable safety profile for the first-line treatment of advanced lung adenocarcinoma. Clinical trial information: NCT04459078.
Durvalumab (D) +/- tremelimumab (T) + chemotherapy (CT) in first-line (1L) metastatic (m) NSCLC: AE management in POSEIDON.
Authors: Cho Byoung Chul , Reinmuth Niels , Luft Alexander , Alatorre-Alexander Jorge , Geater Sarayut Lucien , Trukhin Dmytro , Kim Sang-We , Ursol Grygorii , Hussein Maen A. , Lim Farah Louise , Yang Cheng-Ta , Araujo Luiz H. , Saito Haruhiro , Marotti Miriam , Barrett Karen , Shi Xiaojin , Peters Solange , Garon Edward B. , Mok Tony S. K. , Johnson Melissa Lynne 
Published: June 2022

9035 Background: In the Phase 3 POSEIDON study in 1L mNSCLC, adding T to D+CT resulted in statistically significant improvements in PFS and OS vs CT. No new safety signals were identified and treatment discontinuations due to treatment-related AEs (TRAEs) were similar for the T+D+CT and D+CT arms (15.5% and 14.1%). Here we present details of AEs and their management. Methods: 1013 pts with EGFR/ ALK wild-type mNSCLC were randomized 1:1:1 to 1L T+D+CT, D+CT or CT. Safety was assessed in all treated pts. Results: 330, 334 and 333 pts received T+D+CT, D+CT and CT; 78%, 82% and 74% received at least 4 cycles of platinum-based CT. The most common grade 3/4 TRAEs were hematologic (anemia in 17%, 15% and 20% of pts in the T+D+CT, D+CT and CT arms and neutropenia in 16%, 13% and 12%) and most were managed using standard approaches per local practice; 22%, 18% and 16% of pts received colony stimulating factors and 22%, 21% and 26% received blood transfusions. All grade immune-mediated AEs (imAEs) occurred in 34%, 19% and 5% of pts in the T+D+CT, D+CT and CT arms; a higher incidence of diarrhea/colitis, dermatitis/rash and endocrinopathies was seen with the addition of T to D+CT (Table). Grade 3/4 imAEs occurred in 10%, 7% and 2% of pts in the T+D+CT, D+CT and CT arms, and serious imAEs in 10%, 6% and 1%; imAEs led to discontinuation of any study treatment in 6%, 4% and 0.6%, and led to death in 0.6%, 0.3% and 0%. Most imAEs were low grade and manageable with systemic corticosteroids (received by 26%, 13% and 4% of pts in the T+D+CT, D+CT and CT arms) or endocrine therapy (12%, 8% and 1%). Median time from first dose to onset of imAEs (TTO) was generally > 60 days and the majority of non-endocrine imAEs resolved (Table). Conclusions: In POSEIDON, the safety profile of all regimens was manageable per standard guidelines and in line with the known profiles of D, T+D and CT; the most common grade 3/4 TRAEs were those typically associated with CT. As expected, more imAEs occurred with T+D+CT than D+CT, but the incidence of grade 3 or 4 imAEs, imAE-related deaths and treatment discontinuations due to imAEs was generally similar in the IO arms. T+D did not compromise the ability to administer planned CT. Clinical trial information: NCT03164616. [Table: see text]
Association between immune-related adverse events and microbiome composition in patients with advanced non–small cell lung cancer treated with immunotherapy.
Authors: Tonneau Marion , Richard Corentin , Nolin-Lapalme Alexis , Auclin Edouard , Benlaifaoui Myriam , Ponce Mayra , Al-Saleh Afnan , Blais Normand , Florescu Marie , Tehfe Mustapha , Malo Julie , Messaoudene Meriem , Okuma Yusuke , Hakozaki Taiki , Routy Bertrand 
Published: June 2022

9036 Background: Despite immune-checkpoint inhibitors (ICI) achieving high response rates in patients (pts) with advanced non-small cell lung cancer (NSCLC), immune-related adverse events (irAE) remain an important therapeutic hurdle. The gut microbiome represents a novel prognostic marker of ICI response and early clinical evidence suggests that the microbiome may also regulate the development of irAE. We aimed to assess the association between irAE and the gut microbiome composition in advanced NSCLC pts amenable to ICI. Methods: In this study, we enrolled 464 pts from two independent cohorts (Montreal and Tokyo) with advanced NSCLC treated with ICI monotherapy or combination with chemotherapy. Fecal samples were collected prior to ICI initiation. Metagenomics microbiome profiling and 16S rRNA microbiome sequencing were performed for 81 pts and 133 pts respectively. The irAE were classified as CTCEA grade 0-1 (G0-1 irAE) and grade > 2 (G2-5 irAE). Microbiome composition of both groups was represented using alpha diversity, beta diversity indexes and LEfSe relative abundances. Results: Median follow-up was 28.3 months (mos) and the incidence of G2-5 irAE was 25.1% in the Montreal cohort. For the Tokyo cohort, the median follow-up was 19.6 mos and 30.8% pts developed G2-5 irAE. First, in both cohorts, overall survival (OS) and progression-free survival (PFS) were significantly improved for pts with G2-5 irAE compared to G0-1 irAE (OS: HR: 1.71, p = 0.008 and PFS: HR: 1.65, p < 0.001) and (OS: HR: 2.34, p = 0.001, and PFS: HR = 2.34, p = 0.006) respectively. Second, metagenomics analysis of 81 pts demonstrated a numerical decrease of the alpha diversity in terms of observed species in the G2-5 irAE. Dorea sp CAG 31, Anaerosporobacter mobilis, Butyricicococcus, and Enterococcus faecium were overrepresented in pts with G2-5 irAE. Conversely, Gordonibacter was increased in G0-1 irAE. Next, 16S rRNA profiling from the Tokyo cohort revealed an enrichment of Dorea, Butyricicococcus, and Eubacterium ventriosum in G2-5 irAE . Finally, we observed an enrichment in Dorea and Butyricicococcus in the pts with PFS > 6 months, as observed in the G2-5 irAE group. Conclusions: IrAE correlated with clinical outcome and microbiome composition in two independent cohorts of pts with advanced NSCLC. These results prompt further research on the potential mechanism underling the role of the microbiome in the development of irAE.