bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy and safety of taletrectinib in patients with TKI-naïve or crizotinib-pretreated ROS1-positive non–small cell lung cancer (NSCLC).
Authors: Li Wei , Yang Nong , Ma HuiWen , Fan Huijie , Li Kunyan , Wu Huijuan , Yu Qitao , Wang Yongsheng , Meng Xue , Wang Xicheng , Qin Xintian , Wang Ziping , Liu Yunpeng , Tao Min , Zhuang Wu , Fang Yong , Sun Ping , Lu Kaihua , Wu Jingxun , Zhou Caicun 
Published: June 2022

8572 Background: Taletrectinib (AB-106 / DS-6051b) is a next-generation, potent, CNS- penetrant, selective ROS1 tyrosine kinase inhibitor. The ongoing TRUST study (NCT04395677) is a multicenter, open-label, single-arm, Phase 2 study of taletrectinib in Chinese ROS1-positive NSCLC patients who are TKI -naïve or crizotinib-pretreated. Here we present the updated efficacy and safety results of the study. Methods: The eligible ROS1-positive NSCLC patients were enrolled into either TKI-naïve or crizotinib-pretreated cohorts, and treated with taletrectinib 600mg once daily. The study endpoints included overall response rate (ORR), duration of response (DOR), disease control rate (DCR), overall intracranial response rate (IC-ORR), progression-free survival (PFS), and safety profile. Results: As of the data cutoff date of September 7, 2021, 61 of the 86 stage IV patients enrolled in the study have at least three postbaseline tumor assessment of which 40 patients in the TKI-naïve cohort, and 21 patients in the crizotinib-pretreated cohort (50% patients having at least one prior chemotherapy). In the TKI -naïve cohort, the confirmed ORR by investigators per RECIST 1.1 was 90.0%: [95%CI: 76.3%; 97.2%] (36/40); and the DCR was 95% [95%CI: 83.1%; 99.4%] (38/40). In the crizotinib-pretreated cohort, the confirmed ORR by investigators was 47.6% [95%CI: 25.7%; 70.2%] (10/21); and DCR was 76.2%: [52.8%; 91.8%] (16/21). The mDOR and mPFS are not reached yet for both cohorts. Of 6 patients having brain metastasis and measurable target brain lesions at baseline, the intracranial ORR and IC-DCR were 83.3% and 100%, respectively. Of 4 patients with ROS1 G2032R mutation, 3 patients achieved partial response (PR), and 1 patient achieved stable disease (SD). The most common treatment-related adverse events (TRAEs) include diarrhea, nausea, vomiting, transaminase elevation, anemia, neutrophil count decrease, etc. were Grade 1 or 2, and the most common AEs (below 10%) were ALT/AST increased but reversible. Conclusions: Taletrectinib demonstrated meaningful clinical efficacy in both TKI-naïve and crizotinib-pretreated ROS1 positive NSCLC patients. In particular, taletrectinib showed clinical effectiveness in patients with ROS1 secondary G2032 mutations and patients with brain metastasis. Taletrectinib was well tolerated in this patient population. Clinical trial information: NCT04395677.
Total metabolic tumor volume on 18F-fluorodeoxyglucose-positron emission tomography ([18F]-FDG-PET) scan: A potential prognostic factor in extensive-stage small cell lung cancer.
Authors: Andrini Elisa , Lamberti Giuseppe , Argalia Giulia , Fortunati Emilia , Fanti Stefano , Campana Davide , Ardizzoni Andrea 
Published: June 2022

8574 Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine lung cancer, accounting for 10-15% of all lung cancers, commonly classified in limited stage (LS-SCLC) and extensive stage (ES-SCLC). Despite the introduction of chemoimmunotherapy as new standard first-line therapy for ES-SCLC, the benefit of addition of the programmed-death ligand 1 (PD-L1) inhibitors is limited to a subset of patients, suggesting the importance to identify predictive biomarkers of response. [18F]FDG-PET/CT is commonly used for the staging and therapeutic planning of SCLC patients. Metabolic parameters derived from [18F]FDG-PET could predict patient outcomes by measuring the extension of metabolically active tumor (metabolic tumor volume [MTV]) or its metabolic heterogeneity (total lesion glycolysis [TLG]). Methods: We retrospectively collected patients with pathologically confirmed diagnosis of SCLC, who had undergone an [18F]FDG PET/CT scan within 30 days from the start of first-line treatment for ES-SCLC. Patients with LS-SCLC at diagnosis were included if presenting relapse at pre-treatment scans performed at least 90 days from the end of treatment with radical intent. We calculated metabolic parameters, MTV and TLG, by summing each single lesion’s MTV and TLD respectively. The primary endpoint of the study was overall survival (OS), defined as the time from [18F]FDG PET/CT scan acquisition to death from any cause. Results: A total of 86 SCLC patients ES-SCLC were included. Patients with hyponatremia, hypoalbuminemia and elevated LDH levels were associated with greater number of lesions, greater total MTV, and higher total TLG at [18F]FDG-PET/CT/CT scan. At a median follow-up of 20.9 months, the median OS was 11.1 months. Median survival was longer among patients with Na + ≥135 mEq/L, with normal albumin levels and in those with normal LDH levels and without bone metastases. Patients with low total MTV had longer OS compared with those with high total MTV (11.9 months vs 4.8 months, respectively). High total MTV was independently associated with the risk of death (p < 0.001) but not with the risk of progression. Conclusions: Our preliminary data showed that total MTV could provide prognostic information in patients with ES-SCLC, suggesting a potential role as stratification factor in immunotherapy-based clinical trials.
Antitumor activity of sunvozertinib in NSCLC patients with EGFR Exon20 insertion mutations after platinum and anti-PD(L)1 treatment failures.
Authors: Janne Pasi A. , Wang Mengzhao , Camidge D. Ross , Mitchell Paul , Fang Jian , Nian Weiqi , Chiu Chao-Hua , Zhou Jianying , Zhao Yanqiu , Su Wu-Chou , Yang Tsung-Ying , Zhu Viola Weijia , Millward Michael , Fan Yun , Huang Wen-Tsung , Cheng Ying , Jiang Liyan , Brungs Daniel , Zheng Li , Yang James Chih-Hsin 
Published: June 2022

9015 Background: Platinum-based chemotherapy is the 1st line standard of care for NSCLC patients with EGFR exon 20 insertion mutations (Exon20ins), with anti-PD(L)1 frequently used as well. Here we present anti-tumor activity of sunvozertinib in these patients whose disease had progressed on these therapies from two ongoing phase 1/2 studies (WK-KONG1, NCT03974022 and WU-KONG2, CTR20192097). Based on these data, sunvozertinib was granted the Breakthrough Therapy Designation by both US FDA and China NMPA. Methods: The objective of this study is to characterize the safety and efficacy of sunvozertinib in platinum-pretreated advanced NSCLC patients harboring EGFR Exon20ins, with or without anti-PD(L1) treatment. In addition, the effect of prior treatment on sunvozertinib’s safety and efficacy were explored. Results: As of July 30, 2021, a total of 52 locally advanced or metastatic NSCLC patients harboring EGFR Exon20ins post platinum treatment were enrolled into WU-KONG1 and WU-KONG2 studies, and included in the efficacy analysis set (dose range: 50 mg to 400 mg, once daily). Male/Female: 21/31; Median age 59; Asian/White: 44/8; Prior therapies: median 2.5 (range 1-10); 31% received prior anti-PD(L)1 treatment (all in £ 300 mg cohorts); 40% of the subjects with baseline brain metastasis. Partial response was observed at ≥ 100 mg. At the dose level of 100 mg, 200 mg, 300 mg and 400 mg, confirmed ORR was 50% (1/2), 55.6 % (5/9), 44.8% (13/29) and 22.2% (2/9), respectively. With a median follow-up time of 10.5 months, median DoR was not reached for 200 mg cohort; with a median follow-up of 7 months, median DoR of 300 mg group was 5.6 months. Progression free survival (PFS) rate at 6 months for 100 mg, 200 mg, 300 mg and 400 mg cohorts was 50%, 53.3%, 44.6% and 44.4%, respectively. In patients with/without prior anti-PD(L)1 treatment, comparable efficacy and safety profiles were observed. Conclusions: The data suggest sunvozertinib is active in platinum-pretreated patients with EGFR Exon20ins, irrespective of prior or after anti-PD(L)1 treatment. The updated data will be presented at the meeting. Sunvozertinib is currently in phase 2 pivotal clinical development (NCT03974022 and China CTR20211009). Clinical trial information: NCT03974022.
Identifying prognostic and predictive value of mutations associated with clinical outcomes in first line (1L) patients with advanced or metastatic non–small cell lung cancer (aNSCLC).
Authors: Perez Parente Diego , Cobo-Dols Manuel , Hasan Haroon , Olson Sara , Pal Navdeep , Wilkinson Samantha , La Orden Tévar Beatriz , Pérez Fernández Mar , Provencio-Pulla Mariano 
Published: June 2022

9047 Background: Whilst the impact of certain mutations on aNSCLC survival outcomes has been evaluated, real-world (rw) evidence on its predictive and prognostic value remains limited. We aimed to identify the predictive and prognostic value of non-driver mutations that are deemed to be clinically relevant in aNSCLC. Methods: This retrospective cohort study analysed de-identified electronic medical records from the Flatiron Clinico-Genomic (FCGD) and FoundationCORE™ databases of aNSCLC patients who have initiated 1L cancer immunotherapy (CIT, alone or in combination) or chemotherapy (chemo) under routine care between 2016 and 2021. Propensity-based multivariable models were used to determine associations between mutational status and progression-free survival (rwPFS), overall survival (rwOS) and overall response (rwR). Results: Of 10,795 patients identified, 2,999 met inclusion criteria (1,042 chemo, 1,957 CIT). Among these, 53% were men and 65% were ≥65 years old. Patients mostly had non-squamous histology (68%), a previous history of smoking (95%) and ECOG ≤1 (61%). 58% of patients were diagnosed as de novo. A total of 185 different mutations were identified in this population, and variants of the same mutation were grouped, identifying 58 mutation families. STK11, KEAP1 and CDKN2A/B mutations were significantly associated with all effectiveness outcomes (Table), indicating lower response (rwR OR<1) and shorter survival (rwOS and rwPFS HR>1) in patients harbouring mutated vs. wild type genes. APC and KRAS mutations were only significantly associated with lower rwR, while FGRF and HRAS mutations were related to worse rwPFS and rwOS, respectively. In contrast, a significantly higher likelihood of response or PFS was associated with ATM/R/RX and GATA3 mutations, respectively. Moreover, our results suggest that KRAS mutations potentially have predictive value for PFS in CIT-treated patients. Mutations with prognostic value on clinical outcomes (overall population). HR, hazard ratio; PFS, progression-free survival; OR, odds ratio; OS, overall survival; rw, real-world. Conclusions: STK11, KEAP1 and CDKN2A/B mutations were significantly associated with poor prognosis in all effectiveness outcomes. In addition, KRAS mutations resulted in clinically significant differences in terms of PFS. Further analyses should be conducted to confirm this clinical significance and to evaluate the relevance of these mutations in future clinical trials design.[Table: see text]
Immunophenotypic correlates and response to first-line pembrolizumab among elderly patients with PD-L1-high (≥ 50%) non–small cell lung cancer.
Authors: Barrichello Adriana Paula de Castro , Alessi Joao Victor Machado , Ricciuti Biagio , Pecci Federica , Vaz Victor R. , Lamberti Giuseppe , Turner Madison M. , Pfaff Kathleen L. , Rodig Scott J. , Awad Mark M. 
Published: June 2022

9054 Background: Older age is associated with increased levels of systemic inflammation and altered immunosurveillance in cancer. Whether aging correlates with a distinct immunophenotype or impacts clinical outcomes to first-line pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC) and a PD-L1 tumor proportion score (TPS) of ≥50% is unclear. Methods: We performed a retrospective analysis of patients with NSCLC. Multiplexed immunofluorescence (mIF) for CD8+, PD-1+, PD-1+CD8+ and FOXP3+ was performed to explore tumor immunophenotype. Clinical outcomes were analyzed on a separate cohort of patients with PD-L1-high (TPS of ≥50%) NSCLC (negative for sensitizing genomic alterations in EGFR and ALK) who received treatment with first-line pembrolizumab. Variables demonstrating a univariate signal of association of p < 0.1 were included in the multivariate model. The results were compared in patients < 80 vs ≥80 years old. Results: Among 541 patients with NSCLCs profiled by mIF, the median age was 67 (28-90). When comparing patients < 80y (n = 497) to ≥80y (n = 44), there was no difference in median CD8+ T cells/mm2 (171 vs 148; p = 0.69), PD-1+ immune cells/mm2 (81.1 vs 87.2; p = 0.95), or PD-1+CD8+ T cells/mm2 (18.0 vs 13.1; p = 0.56). NSCLCs from patients ≥80y had a higher median of intratumoral-associated FOXP3+ T cells/mm2 (63.6 vs 91.1; p = 0.03). In a cohort of 271 patients with PD-L1 ≥50% who received first-line pembrolizumab, baseline clinicopathological characteristics were balanced in the < 80y (n = 225) vs ≥80y (n = 46) groups in terms of sex, tobacco use, Eastern Cooperative Oncology Group-Performance Status (ECOG-PS), histology, presence of potentially targetable driver mutations (KRAS, MET, BRAF, HER2, RET), and PD-L1 TPS distribution (50-89% vs ≥90%). Compared to patients < 80y, patients ≥80y had no difference in objective response rate (ORR 39.1% vs 28.2%; p = 0.22) or median progression-free survival (mPFS 6.0 vs 3.0 months; p = 0.16). However, patients ≥80y had a shorter median overall survival (mOS 25.7 vs 7.6 months; p = 0.02), and this result remained significant after adjusting for ECOG-PS. Among those who experienced disease progression on pembrolizumab, patients ≥80y were significantly less likely to receive any second-line systemic therapy compared to patients < 80y (55.6% vs 30.8%; p = 0.008). Conclusions: In patients with NSCLC and PD-L1 ≥50%, the ORR and mPFS to first-line pembrolizumab were similar between patients < vs ≥80 years old. OS was shorter among patients ≥80y, potentially reflecting lower use of second-line therapy in elderly patients after progression on pembrolizumab. The immunophenotypic correlates of NSCLC in older patients need further investigation.
A phase II study of alectinib in combination with bevacizumab as first-line treatment in advanced NSCLC with confirmed ALK fusion: ALEK-B trial.
Authors: Arrieta Oscar Gerardo , Lara Mejía Luis Antonio , Cabrera Luis Antonio , Ramos Maritza , Heredia David Jose , Cruz-Rico Graciela , Salinas Miguel Angel , Cardenas Fernández Daniela , Zatarain-Barron Zyanya Lucía , Cardona Zorrilla Andres Felipe , Remon Masip Jordi , Rosell Rafael 
Published: June 2022

9074 Background: Alectinib is one of the standard treatment options as an upfront therapy in advanced ALK-rearranged non-small-cell lung cancer. However, all patients will eventually progress to target therapy, developing resistance mechanisms. Preclinical data have demonstrated an enhanced activity combining an anti-vascular endothelial growth factor blockade to ALK tyrosine inhibitors. Hence, this study assesses the safety and efficacy of adding bevacizumab to alectinib. Methods: ALEK-B is an open-label phase II trial investigating the efficacy and safety of combined alectinib 600mg daily and bevacizumab 15mg/kg every three weeks in untreated patients with advanced ALK fusion-positive NSCLC. Every patient had confirmed molecular diagnosis by next-generation sequencing (Foundation One CDx) at baseline and progression. The primary endpoint was investigator progression-free survival (PFS). Secondary endpoints were investigator-assessed objective response rate (ORR), intracranial response (ICR), time to central nervous system (CNS) progression, and overall survival. Hence, we present the first interim analysis. Results: Between April 2020 and October 2021, 37 patients were recruited. At the data cut-off of January 31st, 2022, the median follow-up was 15.6 months (IQR 12.5), and an event of disease progression or death occurred in 1 of 36 patients (2.7%). The 12-month event-free survival rate was 97.1% (95% CI 91 to 99), and median PFS was not reached (95% IC 8.9 to NR). Of 36 evaluable patients, 35 had an objective response [ORR 97.2% (95% CI 91 to 99)], and 3 (8.3%) experienced a complete response. Five patients had brain metastases at baseline; among those with measurable disease (n = 4), the ICR was 100%, one complete response, and median duration of response of 11.4 months (IQR 13.1). The 12-month CNS event-free rate was 100%. Any grade adverse events occurred in 86.4% of patients; most common were AST/ALT increase (40.5%), diarrhea (32.4%), blood bilirubin increase (21.6%), anemia (18.9%), and peripheral edema (18.9%). Grade 1-2 hypertension and proteinuria occurred in five (13.5%) patients, and no > G3 occurred. Grade ≥3 treatment-related AEs (TRAEs) occurred in 32.4%; most frequent were AST/ALT increase (27%) and creatinine increase (5.4%). Conclusions: The combination of Alectinib and bevacizumab demonstrated to be a safe and highly effective treatment in terms of response in the first-line setting. Moreover, it seems promising for patients with brain metastases. These results warrant the design of larger confirmatory trials, ideally a randomized phase III study. Clinical trial information: NCT03779191.
Treatment patterns and outcomes in ALK or ROS1 altered NSCLC: An ATOMIC Registry Study.
Authors: Marmarelis Melina Elpi , Grady Connor B. , Liu Geoffrey , Patel Devalben , Liu Stephen V. , Bravo Montenegro Gabriela Liliana , Patil Tejas , Nieva Jorge J. , Herrmann Amanda , Marrone Kristen , Lam Vincent K. , Sun Fangdi , Dowell Jonathan , Velcheti Vamsidhar , Nguyen Matthew , Miller Kelsey Leigh , Iams Wade Thomas , Hwang Wei-Ting , Camidge D. Ross , Aggarwal Charu 
Published: June 2022

9077 Background: New tyrosine kinase inhibitors (TKIs) targeting ALK and ROS1 alterations in non-small cell lung cancer (NSCLC) have emerged over the last decade. Given the rarity of these genetic changes in NSCLC, data on long term outcomes with sequential therapies are limited. Methods: We conducted a multicenter retrospective cohort study of patients with metastatic NSCLC and ALK or ROS1 alterations across 12 Academic Thoracic Oncology Medical Investigators Consortium (ATOMIC) sites between 1/29/2007 and 3/31/2021. Data were abstracted from the electronic medical record. Median time to treatment discontinuation (TTD) of 1st TKI, overall survival (OS), and time to brain metastases were estimated using Kaplan-Meier methodology from start date of 1st TKI. Results: 566 patients with ALK (n = 464) or ROS1 (n = 102) were included. The majority (ALK: 426/464, 92%; ROS1: 88/102, 86%) received a TKI at some point during therapy (1st line TKI n = 262 ALK, 48 ROS1). Crizotinib was the most common 1st TKI (ALK: 57%; ROS1: 88%). Following crizotinib, alectinib (64%) and lorlatinib (41%) were the most common subsequent TKIs for ALK and ROS1, respectively. Alectinib (38%) and entrectinib (10.2%) were the 2nd most common initial TKIs used in ALK and ROS1, respectively. Additional treatment patterns presented in table. With a median follow up time of 31.1 (ALK, 95% CI, 27.6-35.0) and 32.6 (ROS1, 95% CI, 25.7-39.6) months, median OS from start of 1st TKI was 53.3 (ALK, 95% CI, 40.0-68.9) and 42.0 (ROS1, 95% CI, 31.8-NA) months. Out of the 321 patients with brain imaging prior to 1st line therapy, 40% (105/262, ALK) and 39% (23/59, ROS1) had CNS disease. Median time to development of brain metastases from start of 1st TKI in those without previous CNS disease (ALK: 278; ROS1: 58) was 30.0 (ALK, 95% CI, 25.3-39.1) and 27.0 (ROS1, 95% CI, 18.2-NA) months. Median TTD of 1st TKI was 11.2 (ALK) and 10.8 (ROS1) months. Conclusions: This is the largest retrospective cohort of NSCLC patients with ALK or ROS1 rearrangements treated in the real world setting. CNS metastases are common and subset analyses by agent and by year of diagnosis will be presented. Median time to CNS metastasis of > 2 years supports revision of the NCCN guidelines to include regular surveillance brain MRIs in this population. [Table: see text]
Crizotinib in ROS1-rearranged lung cancer (EUCROSS): Updated overall survival.
Authors: Michels Sebastian Yves Friedrich , Franklin Jeremy , Massuti Bartomeu , Sebastian Martin , Felip Enriqueta , Grohé Christian , Rodriguez-Abreu Delvys , Bischoff Helge , Carcereny Enric , Corral Jesús , Insa Amelia , Reck Martin , Rothschild Sacha , Provencio Mariano , Scheffler Matthias , Hellmich Martin , Nogova Lucia , Büttner Reinhard , Rosell Rafael , Wolf Juergen 
Published: June 2022

9078 Background: ROS1 rearrangements are found in approximately 1% of non-small cell lung cancer (NSCLC) patients. Prospective clinical trials showed high efficacy of crizotinib in this molecular subset. Lately, we reported an overall response rate (ORR) of 70% and a median progression-free survival (PFS) of 19.4 months for patients treated within the EUCROSS trial (Michels et al. Clin Oncol, 37(15_suppl):9066-9066, 2019). Here we present an updated analysis of the overall survival. Methods: EUCROSS is a European multi-centre, single arm phase 2 trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria were ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation) and no or stable brain metastases at baseline. Crizotinib was given at a dose of 250 mg twice daily. Primary endpoint of the trial was investigator-assessed ORR in the response-evaluable population (Response Evaluation Criteria in Solid Tumors, version 1.1), with secondary endpoints of PFS and overall survival (OS). Results: Of the 34 patients who received at least one dose of crizotinib (intention-to-treat population, ITT), 30 were included the primary efficacy analysis set (PAS). After a median follow-up of 55.9 months, 13 (43%) patients in the PAS and 15 (44%) in the ITT had died. Median OS was not reached in either group (95% CI, 17.1-NR and 20.3-NR, respectively). OS was negatively correlated with the presence of brain metastases (Log-rank p = 0.1805) and TP53 mutations (Log-rank p = 0.015). Detailed listings of the survival rates are depicted in Table. No new safety signals were observed. Owing to the approval of crizotinib by the European Medicines Agency, all patients who were still on treatment by January 24th 2018 (n=8), were prescribed crizotinib outside the trial. Conclusions: Updated OS highlights the efficacy of crizotinib in patients with ROS1-rearranged lung cancer. Patients with co-occurring TP53 mutations or brain metastases had worse outcomes and represent challenging populations. Clinical trial information: NCT02183870. [Table: see text]