bluuebunny/crossref_metadata_2025_split huggingface dataset:
Determination of clinical benefit among patients with radiological stable disease to immune checkpoint inhibitors.
Authors: Luo Jia , Wu Song , Rizvi Hira , Zhang Qu , Egger Jacklynn V. , Osorio Juan C. , Schoenfeld Adam Jacob , Plodkowski Andrew J. , Ginsberg Michelle S. , Gupta Ashok Kumar , Raja Rajiv , Kris Mark G. , Hellmann Matthew D. 
Published: June 2021

9041 Background: SD is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs) and likely represents a heterogenous mix of responders and non-responders. This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. The ability to distinguish whom among patients with SD is actually benefiting from treatment would facilitate drug development and improve precision in correlative research. Methods: A systematic review was performed to characterize SD in ICI trials. SD and objective response was compared to proliferation index using TCGA gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of NSCLC treated with ICIs and had RECIST assessment. In patients with best overall response (BOR) of SD, serial cutpoints of two variables, % BOR and PFS, were tested to define a subgroup with similar survival as PR-minor (patients with partial response [PR] and % shrinkage < median among responders). Results were then tested in two external validation cohorts (n = 326, n = 381). Results: Among trials of ICIs (59 studies, 14,280 patients), SD ranged from 16-42% in different tumor types and was associated with disease-specific proliferation index (Spearman rho = -0.75, p = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of 1220 patients with NSCLC who were treated with ICIs, 26% had SD, 19% had PR/CR, and 55% had PD. Outcomes among those with SD ranged widely (OS range 0.5-76 months, PFS range 0.2-49 months). The subset of SD with PFS > 6 months and no tumor growth mirrored PR-minor (OS HR 1.0) and was proposed as the definition of “SD-responder”. SD-responders (n = 87) represented 7% (95% CI 6-9%) of the overall population and 28% (95% CI 23-33%) of the SD population. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab. Conclusions: RECIST-defined SD to immunotherapy is common, heterogenous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS > 6 months and no tumor growth (̃1/3 of SD) may be considered “SD responders.” This definition may improve the efficiency of and insight derivable from clinical and translational research.
Subgroup-level network meta-analysis for efficacy of first-line immunotherapy-based treatments in advanced non-small cell lung cancer.
Authors: Wu Fang , Tian Wentao , Cao Chenghui , Ke Jiawen , Tan Nuopei , Cai Yuwen , Zeng Yue , Pan Yue , Liu Xiaohan , Zhao Lishu , Shu Long , Liu Junqi 
Published: June 2021

9064 Background: Immunotherapy has unequal efficacies in populations with different clinical or histological features. This study aims to explore inter-subgroup differences in responses to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and find the optimal treatments for each subgroup. Methods: We performed (network) meta-analyses of phase III random controlled trials, in which efficacies of 10 immunotherapy-based treatments were compared, including anti-programmed death receptor-1 (PD-1) (+chemotherapy), anti-programmed death ligand-1 (PD-L1) (+chemotherapy), anti-PD-L1+anti-cytotoxic T-lymphocyte protein 4 (CTLA-4), anti-PD-1+anti-CTLA-4 (+chemotherapy), anti-CTLA-4+chemotherapy, anti-PD-1+anti-angiogenic therapy (AT)+chemotherapy, and anti-PD-L1+AT+chemotherapy, for 19 subgroups by sex, age, smoking status, metastatic site (liver/brain/bone), histological type (squamous/non-squamous cancer), and PD-L1 expression, using hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and their 95% confidence intervals (CIs). Results: 22 studies comprised of 12678 patients with advanced NSCLC were included in our study. The results showed OS and PFS advantages of immunotherapy-based treatments in 16 out of 19 subgroups comparing with chemotherapy. Never-smokers (OS-HR 0.81, 95% CI 0.55-1.18; PFS-HR 0.73, 95% CI 0.51-1.07), ¡Ý75-year-old patients (OS-HR 0.9, 95% CI 0.71-1.13), and patients with liver metastases (OS-HR 0.88, 95% CI 0.77-1) showed indisposed responses to immunotherapy. In patients with PD-L1 tumor proportion score (TPS)<1%, anti-CTLA-4+anti-PD-1 and anti-PD-1+anti-CTLA-4+chemotherapy had significant OS benefit comparing with anti-PD-L1 monotherapy (HR 0.6, 95% CI 0.44-0.81; HR 0.6, 95% CI 0.41-0.87; respectively) and anti-PD-L1+AT+chemotherapy (HR 0.66, 95% CI 0.48-0.92; HR 0.66, 95% CI 0.45-0.98; respectively). In patients with liver metastases, anti-PD-L1+AT+chemotherapy showed significant PFS advantage comparing with anti-PD-L1+chemotherapy (HR 0.51, 95% CI 0.33-0.77). As for other populations, anti-PD-1+chemotherapy showed wide-ranging promising efficacies in multiple subgroups. Conclusions: Patients with advanced NSCLC generally benefit from immunotherapy. Specific immunotherapy treatments should be applied according to different clinical or histological features. Meanwhile, we expect more preclinical and clinical studies to focus on therapeutic strategies for populations with impaired responses towards immunotherapy. Funding: CSCO-BMS Oncologic Research Foundation (Grant No. Y-BMS2019-100); Guangdong Provincial Key Lab of Translational Medicine in Lung Cancer (Grant No. 2017B030314120) and Guangdong Association of Clinical Trials (GACT); Changsha Science and Technology Bureau (Grant No. kq1907077).
Neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant non-small cell lung cancer (NSCLC) and central nervous system (CNS) involvement: Findings from the SUMMIT basket trial.
Authors: Goldman Jonathan Wade , Viteri Ramirez Santiago , Mahipal Amit , Suga Jennifer Marie Marie , Eli Lisa DeFazio , Lalani Alshad S. , Bryce Richard , Xu Feng , Shah Naisargee , Kabbinavar Fairooz , Boni Valentina , Haley Barbara B. 
Published: June 2021

9068 Background: The phase 2 SUMMIT basket trial (NCT01953926) demonstrated efficacy of neratinib in patients with EGFR exon 18-mutant NSCLC [Boni et al. WCLC 2020]. Neratinib also has documented activity in HER2+ metastatic breast cancer with CNS metastases [Saura et al. SABCS 2020 & J Clin Oncol 2020]. Here we report neratinib efficacy in a subgroup of patients with EGFR exon 18-mutant NSCLC and CNS involvement from SUMMIT. Methods: Patients with EGFR exon 18-mutant NSCLC were treated with single-agent neratinib (240 mg po daily). Prior EGFR tyrosine kinase inhibitors (TKIs), chemotherapy, and checkpoint inhibitors (IO) were allowed. Patients with stable, asymptomatic CNS metastasis were enrolled. Study endpoints: objective response rate (ORR) at week 8 (±1 week); ORR (RECIST 1.1 confirmed); duration of response (DOR); clinical benefit rate (CBR); progression-free survival (PFS); safety; biomarkers. Results: Baseline characteristics of 11 patients with EGFR exon 18-mutant NSCLC: median age 67 (range 56–83) years; ECOG PS 0/1 (45%/55%). Prior lines of therapies: 2 (range 1–3): EGFR TKIs (91%); chemotherapy (55%); IO (27%). 3/11 patients had baseline CNS metastasis and received radiation 8–22 months prior to study enrollment. Best CNS response in these 3 patients was stable disease with overall individual PFS of 1.9 (censored), 6.9 and 9.1 months and OS of 2.6 (censored), 17.7 (censored), and 17.9 months. Efficacy is summarized in Table. Efficacy summary: TKI-pretreated EGFR exon 18-mutant NSCLC cohort receiving neratinib monotherapy. Conclusions: Activity of single-agent neratinib was observed in prior TKI-exposed patients with EGFR exon 18-mutant NSCLC. Despite the small sample size of only 3 patients with baseline CNS metastases, findings suggest a potential role for neratinib as a systemic treatment option for patients with NSCLC and difficult-to-treat uncommon mutations with CNS involvement. The SUMMIT trial continues to enroll patients with EGFR exon 18-mutant NSCLC. Clinical trial information: NCT01953926. [Table: see text]
The effects of tislelizumab treatment on the health-related quality of life of non-small cell lung cancer patients who progressed on a prior platinum-containing regimen.
Authors: Zhou Cai , Huang Dingzhi , Ma Yiyuan , Pan Zhenyu , Barnes Gisoo , Tang Boxiong 
Published: June 2021

9069 Background: Anti-PD-1/L1 therapies have improved overall survival (OS) by 2-4 months vs docetaxel in patients with advanced non−small cell lung cancer (NSCLC) who progressed after receiving a platinum regimen. Tislelizumab, an anti-PD-1 antibody, has been tested as monotherapy in the RATONALE (NCT 03358875) trial, which found that tislelizumab prolonged OS (median OS difference 5.3 months in ITT population) as compared to docetaxel, improved progression-free survival (median 4.1 vs 2.6 months), as well as overall response rate (ORR difference = 14.9%).Here we report health-related quality of life (HRQoL) of patients receiving tislelizumab vs docetaxel in this clinical trial. Methods: NSCLC patients in this open-label, multicenter Phase 3 study were randomized to either the tislelizumab or docetaxel. HRQoL was measured using the QLQ-C30 global health status/quality of life score (GHS/QoL) from EORTC QLQ-C30 as well as the lung cancer specific subscales of the EORTC QLQ-LC13. Descriptive analysis for the GHS/QoL score was performed for baseline through cycle 10; changes from baseline to cycle 12 were examined for the symptom subscales. Results: 805 patients were randomized to tislelizumab (n = 535) or docetaxel (n = 270). Patients were 77% male with an average age of 60 years (range 28-88 years). The compliance rates were mostly > 98% and were similar across arms. The GHS/QoL score in the tislelizumab arm improved relative to baseline from cycles 5 through 10 while declining in cycles 6 through 10 in the docetaxel arm. The tislelizumab arm showed a reduction from baseline at cycle 12 in the symptom scores of coughing, chest pain, and dyspnea while patients in the docetaxel arm experienced an increase in symptoms. Conclusions: The study results show that tislelizumab monotherapy improved HRQoL in patients who previously failed treatment with a platinum containing chemotherapy; this is especially important as the NSCLC patients treated with tislelizumab not only experienced improvements in OS, but also reductions in their symptomology. Clinical trial information: NCT 03358875.
Brigatinib (BRG) in ALK+ crizotinib (CRZ)-refractory non-small cell lung cancer (NSCLC): Final results of the phase 1/2 and phase 2 (ALTA) trials.
Authors: Gettinger Scott N. , Huber Rudolf M. , Kim Dong-Wan , Bazhenova Lyudmila , Holmskov Hansen Karin , Tiseo Marcello , Langer Corey J. , Paz-Ares Luis G. , West Howard , Reckamp Karen L. , Weiss Glen J. , Smit Egbert F. , Hochmair Maximilian , Kim Sang-We , Ahn Myung-Ju , Kim Edward S. , Groen Harry J.M. , Pye Joanna , Vranceanu Florin , Camidge D. Ross 
Published: June 2021

9071 Background: BRG is a kinase inhibitor approved for the treatment of patients (pts) with ALK+ metastatic NSCLC; specific details for BRG use vary by indication and country. We report long-term efficacy and safety results of the Phase 1/2 and Phase 2 (ALTA) trials of BRG. Methods: The Phase 1/2 study was a single-arm, open-label trial (NCT01449461) of BRG 30–300 mg/d in pts with advanced malignancies. ALTA (NCT02094573) randomized pts with CRZ-refractory ALK+ NSCLC to receive BRG at 90 mg qd (arm A) or 180 mg qd with 7-d lead-in at 90 mg (arm B). For the Phase 1/2 study, investigator assessments of confirmed objective response rate (cORR; RECIST v1.1), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety in pts with ALK+ NSCLC are reported. The primary endpoint of ALTA was cORR per investigator; secondary endpoints included cORR per independent review committee (IRC), DoR, PFS, and OS. Results: In the Phase 1/2 study, 137 pts received BRG; of these, 79 pts had ALK+ NSCLC (71/79 had prior CRZ; 28/79 received 180 mg qd [7-d lead-in at 90 mg]; 14/79 received 90 mg qd). In ALTA, 222 pts with CRZ-refractory ALK+ NSCLC were randomized (n = 112/110, arm A/B). At the end of the Phase 1/2 study (Feb 18, 2020), with median 27.7 mo follow-up (̃67 mo after last pt enrolled), 4 pts remained on BRG. At the end of ALTA (Feb 27, 2020), with median 19.6/28.3 mo follow-up in arm A/B (̃53 mo after last pt enrolled), 10/17 pts in arm A/B were still on treatment. Table shows efficacy results from final analyses with long-term follow-up. In ALTA, the IRC-assessed intracranial cORR in pts with measurable baseline brain metastases was 50% (13/26) in arm A and 67% (12/18) in arm B; Kaplan-Meier (KM) estimated median intracranial DoR was 9.4 mo (95% CI, 3.7, not reached [NR]) in arm A and 16.6 mo (3.7, NR) in arm B. With long-term follow-up, no new safety signals were identified. Treatment-emergent adverse events led to dose interruption (Phase 1/2: 59%; ALTA arm A/B: 49%/61%), dose reduction (13%; 8%/33%), or discontinuation (10%; 4%/13%). Conclusions: BRG showed sustained long-term activity, PFS, and manageable safety in pts with CRZ-refractory ALK+ NSCLC. The 180 mg/d dose after 7-d lead-in at 90 mg/d led to numerically higher median PFS and OS. Final results are similar to those reported for other approved ALK tyrosine kinase inhibitors in this setting. Clinical trial information: NCT01449461, NCT02094573. [Table: see text]
Activity of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) in patients (pts) with NSCLC with uncommon EGFR mutations: A real-world cohort study (UpSwinG).
Authors: Miura Satoru , Hsia Te-Chun , Hung Jen-Yu , Jung Hyun Ae , Shih Jin-Yuan , Park Cheol-Kyu , Lee Seung Hyeun , Okamoto Tatsuro , Ahn Hee Kyung , Lee Yong Chul , Sato Yuki , Lee Sung Sook , Mascaux Celine , Daoud Hasan , Maerten Angela , Popat Sanjay 
Published: June 2021

9072 Background: EGFR TKIs are an established treatment (tx) option for pts with EGFR mutation-positive NSCLC with common mutations (Del19 or L858R); however, 7–23% of NSCLC tumors harbor uncommon EGFR mutations, where EGFR TKI efficacy is less established. These mutations are highly heterogeneous, and developments in detection by NGS are helping to identify mutations with little or no clinical data. Methods: In this non-interventional, global, multi-center study (NCT04179890), existing medical or electronic health records were identified for consecutive EGFR TKI-naïve pts with uncommon EGFR mutations (T790M, ex20ins, major uncommon [G719X, L861Q or S768I], ‘other’ or compound mutations) treated with erlotinib, gefitinib, afatinib, osimertinib or other systemic therapy. Endpoints were time to tx failure (TTF), ORR, OS and duration of response (DoR). Results: Overall, 246 pts (median age: 69.5 yrs; Asian: 84%; brain metastases: 8%; ECOG PS ≥2: 16%) were recruited from 9 countries. Most pts (n=226; 92%) received an EGFR TKI as 1st-line therapy; 132 (54%), 105 (43%) and 7 (3%) received afatinib, 1st-gen TKIs and osimertinib, respectively. 57% of pts received >1 line of therapy. Most pts (73%) had a major uncommon mutation, 9% had other mutations and 33% had a compound mutation; these were detected using PCR (75%) or sequencing (25%), mainly based on tissue biopsy (86%). Pathology reports varied in quality, often lacking detail on specific mutations e.g. 21% of ex18 and 72% of ex20ins were undefined. Median TTF and OS with EGFR TKIs were 9.9 and 24.4 mos; ORR was 42%. In pts treated with 1st-line chemotherapy (n=20), median TTF and ORR were 6.6 mos and 41%. Outcomes were most favorable in major uncommon and compound mutations (Table). TTF appeared to be higher with afatinib vs 1st-gen EGFR TKIs. In most mutation categories, median OS was >2 yrs, possibly reflecting high subsequent therapy uptake. Conclusions: In a real-world setting, EGFR TKIs were the preferred tx option in pts with uncommon EGFR mutations; strongest outcomes were seen in major uncommon and compound mutations, and in pts treated with afatinib. Data were in line with recent analyses of afatinib in uncommon mutations. Tx with an EGFR TKI should be considered as standard for most pts with uncommon mutations. Optimal tx for pts with uncommon mutations requires improvements in pathology reports, with more emphasis on NGS methodology and precise definition of mutations. Clinical trial information: NCT04179890. [Table: see text]
Patient-reported symptoms, functioning, and quality of life (QoL) in patients treated with cemiplimab monotherapy for first-line treatment of advanced NSCLC with PD-L1 ≥ 50%: Results from EMPOWER-Lung 1 study.
Authors: Gumus Mahmut , Chen Chieh-I , Ivanescu Cristina , Kilickap Saadettin , Bondarenko Igor , Ozguroglu Mustafa , Gogishvili Miranda , Turk Haci M. , Cicin Irfan , Harnett James , Mastey Vera , Naumann Ulrike , Reaney Matthew , Konidaris Gerasimos , Sasane Medha , Brady Keri , Li Siyu , Gullo Giuseppe , Rietschel Petra , Sezer Ahmet 
Published: June 2021

9078 Background: Cemiplimab, a PD-1 inhibitor, improved survival and progression-free survival vs platinum doublet chemotherapy (chemo) in patients (pts) with advanced NSCLC and PD-ligand(L)1 expression ≥50% in the EMPOWER-Lung 1 Phase 3 study (NCT03088540). Since pts with advanced NSCLC have a high symptom burden that adversely impacts QoL and functioning, these outcomes were evaluated as secondary endpoints in the clinical trial. Methods: Pts with advanced NSCLC with PD-L1 expression ≥50% and ECOG performance status ≤1 were randomized to IV cemiplimab 350 mg Q3W (n=356) or platinum doublet chemo (n=354). At baseline (BL) and day 1 of each treatment cycle (C) to C15, pts were administered the EORTC core questionnaire (QLQ-C30) and its lung cancer specific module (QLQ-LC13) to assess symptoms, functioning, and Global Health Status (GHS)/QoL. In the intent-to-treat population, mixed-effects repeated measures models were used to estimate least squares (LS) mean change from BL on all scales. Kaplan–Meier analysis estimated time to definitive deterioration, defined as worsening ≥10 points from BL observed at all subsequent time points or patient withdrawal after worsening; hazard ratios (HR) with 95% CIs estimated the likelihood of definitive deterioration. Results: BL scores showed moderate to high levels of functioning and low symptom burden. Cemiplimab-treated pts had lower likelihood of definitive deterioration vs chemo on key symptoms of dyspnea, cough, pain in chest, pain in other body parts, fatigue, nausea/vomiting, appetite loss, constipation, and diarrhea vs chemo (all P<.05). Treatment-related symptoms of peripheral neuropathy and alopecia had a lower likelihood of definitive deterioration with cemiplimab vs chemo (both P<.05). Cemiplimab resulted in significantly greater improvements vs chemo on all functioning scales and reduced the likelihood of definitive deterioration as indicated by HR <1 (Table). GHS/QoL improvements with cemiplimab at C2 were maintained to C15; LS mean change (SE) from BL across all timepoints was 7.1 (1.0) for cemiplimab vs 1.7 (1.2) for chemo ( P<.0001). Conclusions: In pts with advanced NSCLC and PD-L1 expression ≥50%, cemiplimab significantly improved GHS/QoL, functioning, and most symptoms vs chemo. Over 1 year of treatment, cemiplimab delayed worsening of key lung cancer symptoms and functioning. Clinical trial information: NCT03088540. [Table: see text]
Real-world patterns of biomarker testing and targeted therapy in metastatic non-small cell lung cancer (mNSCLC) in the community oncology setting.
Authors: Nadler Eric S. , Vasudevan Anupama , Davies Kalatu , Wang Yunfei , Gupta Ravindra , Ogale Sarika 
Published: June 2021

9079 Background: National guidelines recommend biomarker testing in mNSCLC, and targeted therapy is associated with improved outcomes. The aim of this study was to understand the real-world biomarker testing and treatment patterns in the community setting. Methods: This was a retrospective study of adult patients diagnosed with de novo mNSCLC between 01-Jan-2016 and 30-Sep-2019, with follow-up through 31-Dec-2019 using The US Oncology Network structured electronic health records data. Patients who received systemic treatment for mNSCLC were included. Results: A total of 3213 patients were identified with median age 68 years (24, 90+); 52.7% were male and 10% were current smokers. ECOG score was 0-1 in 55.2%; 60% had adenocarcinoma, 16% had squamous cell carcinoma, and the rest had other/unknown histology. Since most of the biomarker-guided therapies were approved after 2016, testing patterns are described for 2017-2019 (n=2257). Overall, 23.6% were not tested for any biomarker (PD-L1 or driver mutation [DM]) at any time during the study period, and only 49% had a biomarker test result prior to 1L treatment. We observed similar patterns when assessing DM specifically; 35.8% were never tested for DM, and only 39.3% had a DM test result prior to 1L treatment. As an example, out of 42 ALK+ patients in this study population, only 5 had test results prior to 1L treatment and only 3 received an ALK inhibitor as their 1L treatment (Table). Similar patterns were observed for the other biomarkers. Conclusions: Despite availability of promising biomarker-based therapies, the lack of adequate testing in the community oncology setting means that not all eligible patients are receiving the most effective therapies upfront. Nearly 61% of patients had no DM test reported before 1L treatment in this mNSCLC cohort (all histologies), and some were determined to be DM positive at a later time, highlighting a missed opportunity to employ the most effective biomarker-directed front-line treatment. Next steps in this study will include assessing patterns by histology. Structured data, which are recorded for clinical management, might have gaps; future research with chart reviews could provide a more comprehensive assessment.[Table: see text]