bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-year outcomes and correlative analyses in patients with non–small cell lung cancer (NSCLC) and a very high PD-L1 tumor proportion score (TPS) ≥ 90% treated with first-line pembrolizumab.
Authors: Ricciuti Biagio , Elkrief Arielle , Alessi Joao Victor Machado , Wang Xinan , Barrichello Adriana Paula de Castro , Pecci Federica , Lamberti Giuseppe , Lindsay James , Sharma Bijaya , Felt Kristen , Nishino Mizuki , Sholl Lynette M. , Rodig Scott J. , Schoenfeld Adam Jacob , Awad Mark M. 
Published: June 2022

9043 Background: Although 1st-line PD-1 monotherapy has improved survival in advanced NSCLC with a PD-L1 TPS ≥50%, responses occur in ̃45% of patients (pts). We previously showed that among pts treated with 1st-line pembrolizumab, clinical outcomes were significantly improved in those with a PD-L1 TPS of ≥90% compared to a TPS of 50-89%. Here, we report the 3-year survival analysis to 1st-line pembrolizumab in pts with a PD-L1 TPS ≥90% vs 50-89%, and characterize genomic and immunophenotypic differences between these PD-L1 expression groups. Methods: Pts with stage IV EGFR/ALK wild-type NSCLC and PD-L1 TPS ≥50% who received 1st-line pembrolizumab at the Dana-Farber Cancer Institute (DFCI) and Memorial Sloan Kettering Cancer Center (MSKCC), with a minimum follow-up of 3 years were included. Comprehensive tumor genomic profiling and multiplexed immunofluorescence (mIF) were performed to examine genomic and immunophenotypic correlates of very high PD-L1 expression on separate cohorts of NSCLC at the DFCI. Results: Among 396 pts, median age was 69, 53.3% were women, 90.1% had a history of tobacco use, 83.6% had a ECOG performance status of 0-1, and 28.8% had a KRAS mutation. At a median follow-up of 42.6 months, median progression-free (mPFS) and overall survival (mOS) in the entire cohort were 5.1 months, and 19.0 months, respectively. When compared to pts with a PD-L1 TPS of 50-89% (N = 252), those with PD-L1 TPS ≥90% (N = 144) had a significantly longer mPFS (6.0 vs 4.5 months, HR 0.67, p < 0.001), and longer mOS (30.2 vs 16.9 months, HR 0.66, p < 0.01). Kaplan-Meier estimates of the 3-year PFS and OS were 24.9% and 47.0% in the PD-L1 TPS ≥90% groups, and 9.4% and 27.7% in the PD-L1 TPS 50-89% group, respectively. A PD-L1 TPS ≥90% was confirmed to be an independent predictor of improved PFS (HR 0.68, p < 0.01) and OS (HR 0.67, p < 0.01) in multivariable analysis. Tumor genomic profiling from a separate cohort of 500 NSCLC samples revealed that mutations in STK11, KEAP1, FBXW7, and CTNNB1 were significantly more frequent in tumors with a PD-L1 TPS of 50-89% compared to those with a PD-L1 TPS ≥90% (q < 0.05). mIF on 91 NSCLCs identified significantly higher CD8+PD1+ T cells and PD-L1+ immune cells in tumors with PD-L1 TPS ≥90% vs 50-89% (p < 0.05). Conclusions: Pembrolizumab monotherapy continues to demonstrate a meaningful long-term survival benefit in pts with advanced NSCLC and a PD-L1 TPS ≥90%. NSCLCs with very high PD-L1 TPS may have a more favorable genomic and immunophenotypic profile. These findings have implications for treatment selection and clinical trial interpretation and design.
Real-world effectiveness of immune checkpoint inhibitors alone or in combination with chemotherapy in metastatic non–small cell lung cancer.
Authors: Hong Lingzhi , Rinsurongkawong Waree , Saad Maliazurina B , Chen Pingjun , Aminu Muhammad , Spelman Amy R. , Negrao Marcelo Vailati , Cascone Tina , Lin Steven H. , Lee Percy , Sepesi Boris , Lewis Jeff , Gibbons Don Lynn , Vaporciyan Ara A. , Lee J. Jack , Le Xiuning , Wu Jia , Heymach John , Zhang Jianjun , Vokes Natalie I 
Published: June 2022

9055 Background: The benefit of combination immune checkpoint inhibitor (ICI) with chemotherapy over ICI monotherapy in non-small cell lung cancer (NSCLC) remains underexplored. Methods: This retrospective cohort included patients with metastatic NSCLC from a single-institution database treated with ICI monotherapy or with chemotherapy between 1/2014-2/2020. Clinical progression-free survival (PFS) and overall survival (OS) were the primary outcomes. Propensity score adjustment for clinical and sociodemographic characteristics was used for analysis of first-line treatment outcomes. Results: A total of 1,139 patients (54% male; median age, 64.9) were included. Adenocarcinoma histology, smoking history, higher PD-L1 expression, and lower metastatic stage associated with improved PFS. However, PD-L1 expression and smoking associated with PFS only in adenocarcinoma (LUAD); squamous (LUSC) patients had shorter PFS independent of PD-L1 and smoking history (PD-L1 > 50% vs 1-49%: LUAD P < 0.001; LUSC P = 0.69; Former vs never smoker: LUAD P = 0.008; LUSC P = 0.89). In first-line patients (n = 680), treatment with ICI plus chemotherapy (ICI-chemo) associated with higher progression-free rates at 3 and 6 months compared with ICI-monotherapy (ICI-chemo vs ICI-mono: 3-month PFS, 85.2% vs 68.8%, P = 0.001; 6-month PFS, 66.4% vs 52.6%, P = 0.008). However, there was no difference overall in PFS or OS in either the full or propensity-matched cohort. Treatment with ICI and chemotherapy concurrently vs sequentially was associated with similar PFS (log-rank P = 0.12). Conclusions: In this real-world cohort, the addition of chemotherapy to ICIs may protect against early progression but does not influence long-term outcomes. Treatment with sequential vs concurrent ICI and chemotherapy produced similar outcomes. These findings suggest that combination therapy may maximally benefit patients at risk of early progression.
Immunotherapy and chemo-immunotherapy for non–small cell lung cancer with novel actionable oncogenic driver alterations.
Authors: Mazzeo Laura , Beninato Teresa , Pircher Chiara Carlotta , Brambilla Marta , Manglaviti Sara , De Toma Alessandro , Galli Giulia , Prelaj Arsela , Ferrara Roberto , Proto Claudia , Lo Russo Giuseppe , Ganzinelli Monica , Garassino Marina Chiara , Marchetti Paolo , De Braud Filippo G. , Occhipinti Mario 
Published: June 2022

9057 Background: Immune checkpoint inhibitors (IO) single agent or in combination with platinum chemotherapy (CT-IO) are standard of care for Stage IV non-small cell lung cancer (NSCLC) according to PD-L1 expression. While the efficacy of IO among patients (pts) with common EGFR and ALK alterations appears to be limited, its activity in pts with novel oncogenic drivers alterations is not well characterized. Compared to non-oncogene-addicted NSCLC, the overall response rate (ORR) seems to be similar in BRAF and c-MET altered NSCLC, lower in RET altered NSCLC, while data are less consistent in HER2 and EGFR exon 20 (EGFRex20) altered NSCLCs. Methods: From January 2016 to January 2022, we retrospectively enrolled pts with Stage IV NSCLC that received IO or combination CT– IO in any line, ECOG PS 0 - 2 and detection of MET exon 14 skipping mutations (METex14), BRAF mutations (V600E or non-V600E), RET rearrangement, HER2 point mutations (HER2mut)/exon 20 insertions (HER2ex20) or uncommon EGFR mutations (uEGFRmut)/EGFRex20. A review of clinicopathologic and molecular features and an analysis of response to combination or single-agent IO were conducted. Results: Among sixty-four pts enrolled, 20 (31%) had METex14, 19 (30%) had EGFR alterations [12 (19%) EGFRex20, 7 (11%) uEGFRmut], 8 (12%) had BRAF mutation (3 V600E and 5 non-V600E), 13(20%) had HER2 alterations [7 (11%) HER2ex20, 6 (10%) HER2mut] and 4 (6%) were RET rearranged. 43 received IO single agent and 21 received CT-IO. With a median follow up of 22 months (m), median progression free survival (mPFS) was 5.40 m (0.95 CI 4.73-6.9) overall, 6.77m in CT-IO arm (0.95 CI 5.37-NA) and 5.10m in IO arm (0.95 CI 2.60-6.7), with a trend to better mPFS for CT-IO (p 0.054). Regarding specific mutations irrespectively from treatment arm, NSCLC harboring METex14 showed a mPFS of 5.33 m (0.95 CI, 2.30-13.9), BRAF 9.9 m (0.95 CI, 6.70-NA), EGFR 4.93 m (0.95 CI, 1.80-6.9), HER2 11.4 (0.95 CI, 4.2-NA), RET 5.28 (0.95 CI, 1.42-NA). Disease control rate (DCR) was better in the CT-IO arm vs IO one in the overall population (84.2% vs 50%, p 0.013). Conclusions: Novel driver alterations seem to show a benefit from IO treatments. CT-IO seems to have a better outcome in terms of DCR. Therefore, IO-based treatment should be evaluated also in tumors harboring novel driver alterations. [Table: see text]
Association of early tumor growth rate and survival outcomes in first-line metastatic non–small cell lung cancer (mNSCLC).
Authors: Fojo Antonio Tito , Brown Kevin , Grootendorst Diederik J. , KOTAPATI SRIVIDYA , Fronheiser Matthew , Tran Phuong , Rizzo Jasmine I. , Leung David , Micsinai Balan Mariann , Kald.Abdallah@Bms.Com No Firstname , Zhao Binsheng , Schwartz Lawrence Howard 
Published: June 2022

9063 Background: Tumor growth rates ( g) estimated using imaging measurements, have been associated with overall survival (OS) and progression-free survival (PFS) in patients with mNSCLC, including those treated with first-line immunotherapy (1L IO) or chemotherapy (chemo). Here, we evaluated whether early g estimates within 18 weeks of first treatment dose are associated with survival outcomes for 1L treatment in mNSCLC. Methods: This was a retrospective analysis of data from patients randomized to either nivolumab+ipilimumab (NIVO+IPI) or chemo in CheckMate 227 Part 1 (NCT02477826), or NIVO+IPI+chemo or chemo alone in CheckMate 9LA (NCT03215706). Tumor assessments were performed by blinded independent central review using RECIST v 1.1 at baseline, every 6 weeks for the first 48 weeks and then every 12 weeks until disease progression. The analysis included patients with at least 3 measurable timepoints, including baseline, week 6, week 12, and/or week 18. If a patient did not have a week 18 measurement, the first three measurements alone were used. To derive the median early g, sum of longest diameters (SLD), based on baseline, weeks 6, 12 and/or 18 assessments, and time relative to baseline were fitted to the model defined by sum of exponential growth (g) and decay (d): SLD (t) = exp (–d x t) + exp (g x t) – 1. OS and PFS were estimated using Kaplan-Meier methodology. Results: In the two studies, 865/1166 (75%) of randomized patients in CheckMate 227 Part 1 and 562/719 (78%) in CheckMate 9LA had evaluable tumor growth rate data (Table). The median early g at weeks 12 and 18 was numerically lower for the IO-containing arm vs chemo arm in both studies (Table). Patients with lower growth rate at week 12 or week 18 ( g in first quartile [Q1]) had better OS relative to those with higher rate ( g in fourth quartile [Q4]) across all treatment arms (Table). A similar trend was observed for PFS. Conclusions: Early g estimates based on 2 or 3 post-baseline tumor assessment timepoints were associated with longer-term survival outcomes for 1L treatment of mNSCLC and could discern efficacy outcomes. These findings provide the foundation for further research, which may incorporate volumetric segmentations of measurable lesions and radiomic feature changes to further explore indicators of patient outcomes that could inform future clinical trials and clinical practice.[Table: see text]
Brigatinib in Japanese patients (pts) with ALK+ NSCLC: Final results from the phase 2 J-ALTA trial.
Authors: Zhang Pingkuan , Kumagai Toru , Yoshida Tatsuya , Nishio Makoto , Toyozawa Ryo , Seto Takashi , Nakagawa Kazuhiko , Ohe Yuichiro , Yamamoto Nobuyuki , Kudou Kentarou , Asato Takayuki , Goto Koichi 
Published: June 2022

9075 Background: In previous J-ALTA (NCT03410108) analyses, brigatinib demonstrated substantial efficacy and manageable safety in pts with TKI-refractory and TKI-naive ALK+ NSCLC. We report the final J-ALTA results. Methods: J-ALTA was a single arm, multicenter, open-label study that included ALK TKI-naive and -refractory NSCLC expansion parts. The main cohort within the refractory part was a group with alectinib-refractory NSCLC. Primary endpoints: IRC-assessed confirmed ORR in the alectinib-refractory cohort; IRC-assessed 12-month PFS in the TKI-naive cohort. Secondary endpoints included confirmed ORR (IRC-assessed in the total refractory cohort; investigator-assessed in all cohorts); DoR, PFS, DCR, and iPFS by IRC; and safety. Final analyses were performed following last pt last contact. Results: A total of 104 pts were enrolled; 72 had TKI-refractory (56% female; median age, 53.0 y) and 32 had TKI-naive (53% female; median age, 60.5 y) NSCLC. As of 28 July, 2021 (last pt last contact), median follow-up was 24.2 mo in the refractory cohort (alectinib-refractory subgroup [n = 47], 23.0 mo) and 22.1 mo in the TKI-naive cohort. Confirmed ORR was 34% (95% CI: 21–49) by IRC with 16 partial responses (PR) in the alectinib-refractory cohort and 32% (21–44; 22 PR) in the total refractory cohort. In the TKI-naive cohort, IRC-assessed 24-mo PFS was 73% (90% CI: 55–85); median PFS was not mature. Additional efficacy analyses are reported in Table. TEAEs were reported in all 104 pts (most common: increased CPK, 79%; hypertension, 48%; diarrhea, 47%). Grade ≥3 TEAEs were reported in 68% and 91% of pts in the TKI-refractory and -naive cohorts, respectively; most commonly (TKI-refractory/naive) elevated CPK, 24%/50%; elevated lipase, 15%/19%; hypertension, 11%/34%. Pneumonitis was mandated to be reported as an SAE regardless of severity and was the only SAE reported in > 5% of pts (refractory, n = 5 [7%; early onset, 1]; naive, n = 4 [13%; early onset, 0]). TEAEs led to dose interruption/reduction/discontinuation in 63%/31%/7% of pts in the TKI-refractory cohort and 94%/69%/0% in the TKI-naive cohort. Conclusions: Final efficacy and safety results in pts with TKI-refractory and -naive NSCLC were consistent with previous J-ALTA analyses. No new safety signals were observed in either cohort. Brigatinib demonstrated a favorable benefit-risk profile and is an important option for Japanese pts with ALK+ NSCLC regardless of TKI treatment history. Clinical trial information: NCT03410108. [Table: see text]
Efficacy of dabrafenib-trametinib combination in BRAF V600E-mutated metastatic non–small cell lung cancer: Results of the IFCT-2004 BLaDE cohort.
Authors: Swalduz Aurélie , Beau-Faller Michele , Planchard David , Mazieres Julien , Bayle Sophie , Debieuvre Didier , Fallet Vincent , Geier Margaux , Cortot Alexis B , Couraud Sebastien , Daniel Catherine , Pichon Eric , Missy Pascale , Morin Franck , Westeel Virginie , Auliac Jean-Bernard , Veillon Remi 
Published: June 2022

9082 Background: BRAF V600E mutations occur up to 2% of advanced non-small cell lung (NSCLC). Dabrafenib-trametinib (D-T) combination was associated with improved OS rates in phase II study and was approved in the 1st-line setting and further. The IFCT-2004 BLaDE study reports the D-T combination efficacy in a large French real-world multicenter cohort of advanced BRAF V600E-mutated NSCLC. Methods: Patients (pts) with advanced NSCLC harboring BRAF V600E mutation diagnosed between 01.01.2016 and 31.12.2019 and treated with D-T combination (D 300 mg + T 2 mg daily) whatever the treatment line were included. Demographic, clinical, pathological data were collected as well as data of efficacy and reason of treatment discontinuation. The primary endpoint was 12 months-OS rate in pts receiving the D-T as 2nd-line or subsequent treatment (L2+). Results: 163 pts were included in 54 centers through 32 national testing labs: 50.3 % were female, 30.2% never-smokers, 95.1 % had adenocarcinoma and PDL1 was > 1% in 78.2%. Median age was 68.3 years. At D-T initiation, 80.8 % of pts were PS 0/1, 93.9 % were stage IIIB/C ineligible for surgery or local therapy and IV, 20.9% had brain metastases and 27% received D+T as 1st line treatment (L1). At the data cutoff (30.06.2021), median (m) follow-up was 27.4 months [95% CI 22.2-31.9] and 47 pts (28.8%) remained on study treatment. 12 months-OS rate in pts receiving D+T in L2+ (n = 119) was 67.4% [95% CI 57.8-75.3] with a median progression-free survival (mPFS) of 10.4 months [95% CI 7.3-13.1]. In the 44 pts receiving D+T in L1, 12 months-OS rate was also 67.4% [95% CI 51.2-79.3] with a mPFS of 18.2 months [95% CI 7.7-21.3]. Objective response rates were 73.8% [95% CI 65.5 - 82.2] and 82.9% [95% CI 71.4 - 94.4], disease progression was observed as best response in 3.7% [95% CI 0.1 - 7.3] and 0% in L2+ and L1, respectively. Other efficacy results are detailed in the table. D-T discontinuation for toxicity was reported in 10.3% of pts. 51.2% and 43.7% of pts received subsequent treatment in L2+ and L1 respectively. For L2+ pts, subsequent treatments were immunotherapy (IO)-based in 37.2 % and chemotherapy in 58.3%. For L1 pts, subsequent treatments were (IO)-based in 42.9% and chemotherapy in 42.7%. Conclusions: Our series confirms significant efficacy of D-T combination in BRAF V600E-mutated metastatic NSCLC. These results in real-world conditions are consistent with registration studies but also support its use in 1st line setting. [Table: see text]
A multicenter real-world study of tumor-derived DNA from cerebrospinal fluid in genomic profiling of NSCLC with central nervous system metastases.
Authors: Mu Yongping , Guo Wei , Zhang Xia , Wang Kai , Yuan Mingming , Chen Rongrong , Bai Jun , Hu Qun 
Published: June 2022

9087 Background: Genomic profiling of cerebrospinal fluid (CSF) could be used to detect actionable mutations to guide the clinical treatment of NSCLC patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in a real-world setting can further confirms the potential of CSF in genotyping for guiding therapy in clinical practice. Methods: A total of 1097 samples were collected from 773 treated NSCLC patients with CNS metastases in a real-world setting, including 117(10.67%) CSF samples, 287(26.16%) tissue samples and 693(63.17%) plasma samples. All samples were subjected to the targeted next-generation sequencing of 1021 cancer-relevant genes. Results: Of these 1097 treated samples, somatic alterations were identified in 112 (95.72%) of the CSF samples, comparing with 287 (100%) of tumor tissue samples and 592 (85.43%) of plasma. Among the tumor tissue samples, 242 were non-intracranial tissues, which could not reveal the unique genetic profiles of intracranial metastases. The median of maximal somatic allele frequency of CSF samples (72.35%) was significantly higher than those of plasma (1.30%) and tumor tissues (37.30%) (all p<0.001). In the thirty-two pairs CSF and plasma samples tested simultaneously, 442 alterations were detected, of which 377 were detected in CSFs and 92 in plasma. 27 alterations could be detected in both plasma and CSF, 65 were not detected in CSFs and 350 were not in plasma, the same alterations were 10.91% (27/442). For SNV or InDel, 220 mutations were detected, of which 155 were detected in CSFs and 89 in plasma, the same mutations were 10.91% (24/220). For CNVs, 216 CNV alterations were detected, of which 216 were detected in CSFs and only one in plasma. We compared actionable mutation of these 1097 treated samples to further analyze the detection capability of actionable mutations of CSF samples in this real-world setting (Table). Compared with plasma, the detection rates of all actionable mutation and actionable EGFR in CSF were significantly higher than those in plasma samples (93.16% vs. 53.97% for all actionable mutation, 83.76% vs. 39.54% for EGFR, all p<0.001).Conclusions: This real-world large cohort study verified that CSF had higher sensitivity than plasma for identifying actionable mutations. In the process of multiple comparison, it can be seen that CSF is better than plasma in detecting alterations, especially in detecting CNV alteration. CSF can be used as a substitute in genomic profiling for NSCLC patients with CNS metastases when there is no intracranial tumor tissue.[Table: see text]
Demographic and socioeconomic factors associated with stage at diagnosis in non–small cell lung cancer: An NCDB analysis.
Authors: Verplancke Kiana , Taylor Alexandra , Gallegos Jillian Marie , McMahon Kevin , Creech Zachary , Truong Gia Thinh , Silberstein Peter T. , Dahl Mary Elizabeth 
Published: June 2022

9132 Background: There were 2.21 million new diagnoses of lung cancer worldwide in 2020, accounting for approximately 25% of all cancer related deaths. A factor that impacts the overall mortality of lung cancer is the stage at initial presentation for diagnosis. Current 5-year survival estimates of non-small cell (NSC) lung cancer range from 73% in early-stage disease to 13% in advanced disease. The stark differences in survival rate in early and late disease, highlight the importance of determining if socioeconomic and demographic factors impact the stage of cancer at diagnosis. This study sought to determine if certain socioeconomic and demographic factors are associated with receiving an early (Stage 0-I) or delayed (Stage IV) diagnosis of NSC lung cancer. Methods: Using the National Cancer Database, 1,149,539 patients were identified as having a NCDB Analytic Stage Group diagnosis of Stage 0-I (early) vs Stage IV (delayed/advanced) NSC lung cancer between 2004 and 2018. Using SPSS statistics 27, patients with early and delayed diagnoses were compared to each other based on certain characteristics including sex, race, ethnicity, and level of education. Results were analyzed using multivariate and chi square analyses, as well as one-way ANOVA. Results: We identified significant differences (p <.005) between stage at presentation and certain socioeconomic factors. Females were 70% less likely to be diagnosed with advanced disease in comparison to males (p <.001, 95% CI =.697-.708). African Americans and Native Americans were more likely to present with advanced disease in comparison to white patients (p <.001, 95% CI = 1.407-1.449 and 1.046 – 1.235, respectively). Hispanic patients were 49.3% more likely to present with advanced disease than non-Hispanic patients (p <.001, 95% CI = 1.389 – 1.605). Patients with at least one comorbidity (CCI score ≥ 1) were less likely to present with advanced disease (p <.001). Those who lived in a zip code where 21% or more of the residents lacked a high school degree were more likely to present with stage IV disease, in comparison to patients who lived in a zip code where less than 20.9% of its residents did not graduate from high school (p <.001). Conclusions: Demographic and socioeconomic factors associated with a delayed diagnosis of NSC lung cancer include male sex, non-white race, being Hispanic, having no comorbidities, and living in a zip code where 21% or more residents have no high school degree.