bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anlotinib plus S-1 for patients with EGFR mutation-negative advanced squamous cell lung cancer with poor performance status after second or more -line treatment.
Authors: Xie Xiaohong , Wang Fei , Liu Ming , Lin Xinqing , Qin Yinyin , Xie Zhanhong , Zhang Jiexia , Ouyang Ming , Zhou Chengzhi 
Published: May 2020

e21665 Background: The study aimed to analyze the efficacy and safety of combination regimen of anlotinib and S-1 for Chinese patients with EGFR mutation-negative advanced squamous cell lung cancer (SqCLC) with poor performance status (PS, 2-3) after second-or-more-line treatment. Methods: Clinical data of 32 SqCLC patients with PS scores of 2-3 treated in the First Affiliated Hospital of Guangzhou Medical University between Jan.1, 2018 to Sep.31, 2019 who failed second-or-more-line treatment were analyzed retrospectively. The patients were divided into two treatment groups: anlotinib (12mg) plus S-1 (25mg) combination group and S1 (12mg) monotherapy group. The efficacy and adverse reactions of the two groups were compared. Results: In terms of the short-term efficacy, there was no significant difference in objective response rate (ORR) (16.7% vs 5.0%, p= 0.54), and disease control rate (DCR) (66.7% vs 55.0%, p= 0.713) between the two groups. As for the long-term efficacy, there was no significant difference in progression-free survival (PFS) between the two groups (5.19 ±1.13 months vs 3.17 ±0.42 months, p= 0.062). the overall survival (OS) of patients in the combination group was longer than S1 group (10.0 ±1.14 months vs 6.37 ±0.47 months, p= 0.042). Conclusions: SqCLC patients with higher PS scores still benefit from anlotinib and S-1 combination regimen, even after they failed second-line or above systemic treatment. [Table: see text]
The efficacy and safety of EGFR-TKI combined with chemotherapy in non-small cell lung cancer (NSCLC) patients with EGFR co-mutation with other oncogenic alterations.
Authors: Yu Qitao , Jiang Wei , Zeng Aiping , Qiu Hongtu , Qi Chuang , Zhang Xing 
Published: May 2020

e21666 Background: Previous studies indicated primary resistance to EGFR-TKIs might occur in EGFR co-mutation with other oncogenic alterations, including TP53, KRAS, PIK3CA and so on. However, the optimal therapeutic regimens for EGFR co-mutation other oncogenic alterations were still unknown. This respective observation study aimed to evaluate the efficacy and safety of EGFR-TKIs combined with chemotherapy in this sub-population, in order to offer new treatments in clinical practice. Methods: In this retrospectively study, from March 2017 to November 2019 advanced NSCLC patients with EGFR co-mutation with other oncogenic alterations in Medical Oncology of Respiratory, Affiliated Tumor Hospital of Guangxi Medical University were screened for eligibility. All included patients were administrated with EGFR-TKIs combined with platinum-based chemotherapy or EGFR-TKIs monotherapy. The clinicopathological data of the patients, and the efficacy and safety of treatment were accorded for statistic analysis. The Kaplan-Meier method was used to estimate median PFS and OS. For all analyses, p value < 0.05 was considered statistically significant, and confidence interval use 95% confidence level. The primary outcome was Progression-free survival (PFS), and Overall survival (OS), Disease control rate (DCR) and safety profile were considered to be the secondary endpoints. Results: Total 23 patients were enrolled in this retrospectively study. The median age of the combination and monotherapy group was 58.7± 8.8 and 58.9 ± 13.5years, respectively. The frequency of female patients was 53.8% and 40% in monotherapy and combination group, respectively. The median PFS (mPFS) was 5.03 months (95% CI: 1.16- 8.9) and not reach in combination therapy group (P = 0.004). No significantly different in mOS was observed in two groups (P = 0.244). The DCR was 92.3% and 100% in monotherapy and combination group, respectively. In combination group, the common adverse events of grade 1 or 2 were adverse reactions of the blood system and rash (40%). Treatment-related grade 3 or 4 toxicity appeared in 3 patients and no patients harbored treatment-related above grade 4 side effects. No cases of treatment-related death occurred. Conclusions: EGFR-TKIs combined with chemotherapy was effective in NSLCL patients with EGFR co-mutation with other oncogenic alterations and side-effects were tolerable. The outcomes of this study should be confirmed by prospective clinical trials in future.
Different efficacy of osimertinib in pre-TKI treated NSCLC patients with brain metastases harboring EGFR exon 19del and L858R mutant.
Authors: Li Xuanzong , Wang Ruozheng , Zou Bing , Zhang Dai , Yu Jinming , Wang Linlin 
Published: May 2020

e21667 Background: Previous studies suggested that the efficacy of osimertinib was better in patients with epidermal growth factor receptor ( EGFR) exon 19 deletion (ex19del) than exon 21 Leu858Arg (L858R). However, the differential clinical outcomes of osimertinib in previous tyrosine kinase inhibitors (TKIs) treated non-small-cell lung cancer (NSCLC) patients with brain metastases (BrMs) according to the two different common EGFR genotypes remains undetermined. Methods: We retrospectively collected EGFR mutant (ex19del and L858R) NSCLC patients with BrMs and received osimertinib treatment between Jan 2016 and Feb 2019 in our hospital. Other eligible standards including Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, osimertinib 80mg monotherapy and neurologic symptoms existing was permitted to enroll in our study. Results: 78 patients with EGFR mutant NSCLC and BrMs were included in the study. EGFR mutation types were ex19del in 55% of patients (43/78) and L858R in 45% of patients (35/78). All of patients received at least one prior EGFR-TKI therapy, among which 46% (36/78) had gefitinib, 49% (38/78) had erlotinib, 19% (15/78) had icotinib. T790M status at osimertinib initiation was positive in 81% of patients (63/78), negative in 4% (3/78), unknown in 15% (12/78). The systemic objective response rate (ORR) was 46%. There was no apparent difference in systemic ORR (49% vs 43%, P = 0.598) between ex19del group and L858R group. The median progression free survival (PFS) and overall survival (OS) were 7.0 (range 4.7-9.3) and 18.8 (range 14.0-23.5) months for all patients. The median PFS in the ex19del and L858R subgroups was 9.1 (range 6.0-12.1) months and 5.3 (range 3.4-7.2) months, respectively ( P = 0.031). The median OS in the ex19del and L858R subgroups was 26.0 (range 13.7-38.3) months and 13.9 (range 7.7-20.2) months, respectively ( P = 0.033). Multivariate analysis identified L858R and ECOG PS 2 as poor independent predictors to the PFS and OS. Conclusions: The efficacy of osimertinib was associated with EGFR genotypes in pre-TKI treated NSCLC patients with BrMs, and L858R maybe an independent bad factor for long-term outcomes of osimertinib.
Patterns of disease progression to checkpoint inhibitor immunotherapy in patients with stage IV non-small cell lung cancer.
Authors: Fei Naomi , Attia Christina , Almubarak Mohammed , Ma Patrick C. , Mattes Malcolm David 
Published: May 2020

e21674 Background: The purpose of this study was to assess patterns of disease progression for patients with metastatic non-small cell lung cancer (NSCLC) on checkpoint inhibitor immunotherapy in order to help guide effective use of targeted radiation therapy to sites of gross disease most likely to progress. Methods: This single center, retrospective study included all patients diagnosed with Stage IV NSCLC between June 2015 and February 2019 who received at least 2 cycles of nivolumab, pembrolizumab, or atezolizumab, with or without concurrent chemotherapy. Immune RECIST criteria were used to assess patterns of disease progression, and progression-free survival (PFS), excluding irradiated tumors. Descriptive statistics were used to report baseline patient and tumor characteristics. The Chi square and log-rank tests were used to determine whether any baseline clinical characteristics were associated with progressive disease in initial sites only (vs. new or combined sites), and PFS, respectively. Factors assessed included initial metastatic sites, tumor histology, performance status, PD-L1 expression, untreated primary tumor, history of brain metastasis, number of metastatic sites involved, and use of concurrent chemo-immunotherapy. Results: Among 143 eligible patients with a median follow-up of 11 months, 97 (68%) developed disease progression. Of these, 67 patients (69.1%) progressed only at initial disease site(s), 10 patients (10.3%) progressed only at new disease site(s), and 20 patients (20.6%) progressed in both initial and new sites. Rates of disease progression based on tumor location were higher for liver (64%) and lung metastases (61%) than for other metastatic sites (33-36%) or the primary tumor (24%). Only higher PD-L1 expression ( p= 0.002) and absence of lung metastasis ( p= 0.048) at baseline were associated with improved PFS. No baseline characteristics significantly impacted the probability of initial disease site-only progression, though a trend was observed for untreated primary tumor (72% vs. 56%, p= 0.169). Conclusions: The dominant pattern of disease progression for patients with metastatic NSCLC on checkpoint inhibitor immunotherapy is in the initial sites of disease alone, whereas only 10% of patients progressed in new disease site(s) alone, suggesting a potential role for local radiation therapy as a complementary treatment modality. Pre-treatment patient and tumor characteristics did not predict patients most likely to benefit.
Phase I dose escalation study of immunoconjugate L-DOS47 in combination with pemetrexed/carboplatin in non-squamous non-small cell lung cancer (NSCLC) patients.
Authors: Dowlati Afshin , Belani Chandra Prakash , Simon George R. , Chao Heman , Piha-Paul Sarina Anne 
Published: May 2020

e21680 Background: L-DOS47, a cancer therapeutic designed to exploit the acidic tumour extracellular environment, consists of urease conjugated to an anti-CEACAM6 camelid monoclonal antibody. The antibody serves as a targeting agent to deliver urease to tumor sites, while the urease enzyme converts urea, an abundant natural metabolite, into ammonia and generates a local pH increase. The combined effect of ammonia toxicity and pH increase is cytotoxic to cancer cells. An additive cytotoxic effect of L-DOS47 and pemetrexed/carboplatin has been observed against the A549 human lung adenocarcinoma cell line. L-DOS47 has been shown in a previous phase I clinical trial to be safe and well tolerated at doses up to 13.55 µg/kg. The current phase I study was designed to define the maximum tolerated dose of L-DOS47 in combination with pemetrexed/carboplatin. Methods: Stage IV (TNM M1a and M1b) histologically confirmed non-squamous NSCLC patients (aged ≥18 yrs, ECOG PS ≤1) received up to four cycles of L-DOS47 in combination with standard of care doses of pemetrexed/carboplatin. L-DOS47 was administered weekly over 21 days in each treatment cycle. Seven planned dosing cohorts (0.59, 0.78, 1.5, 3.0, 6.0, 9.0, 12.0 μg/kg) employed a standard 3+3 design for the first two and the last two cohorts, and an accelerated 1 + 2 design for the middle three cohorts. Dose levels of L-DOS47 were escalated following a review of safety data by the Trial Steering Committee. Results: Fourteen (14) patients were enrolled across 6 dosing cohorts before recruitment was halted. Median age was 65.1 years, with 50.0% male and 78.6% Caucasian. 57.1% of patients had an ECOG score of 0, and 42.9% had an ECOG score of 1. The maximum tolerated dose (MTD) could not be determined as none of the patients experienced a dose limiting toxicity (DLT). 50.0% of patients experienced at least one treatment emergent adverse event (TEAE) assessed as study drug-related, with 14.3% of patients experiencing at least one grade 3/4 drug-related toxicity. Of 12 patients evaluable for efficacy, 5 patients (41.7%) had a partial response (PR), 4 patients (33.3%) experienced stable disease (SD) and 3 patients (25.0%) had progressive disease (PD). The objective response rate is 41.7%. The clinical benefit rate is 75.0%. Conclusions: L-DOS47, in combination with pemetrexed/carboplatin, appears to be well tolerated with promising anti-tumor activity against non-squamous NSCLC. Clinical trial information: NCT02309892.
3rd-line anaplastic lymphoma kinase (ALK) inhibitors (ALKi) in advanced non-small cell lung cancer (aNSCLC): Real-world comparison to non-ALKi therapy.
Authors: Maimon Natalie , Dudnik Elizabeth , Rottenberg Yakir , Popovits-Hadari Noa , Asna Noam , Wollner Mira , Zer Alona , Gottfried Maya , Mishaeli Moshe , Rovitsky-Gelis Yulia , Lobachov Anastasiya , Onn Amir , Urban Damien , Moskovitz Mor Tal , Bar Jair ,   Israel Lung Cancer Group
Published: May 2020

e21685 Background: ALKi represent the standard 1st- and 2nd -line treatment (Tx) for ALK+ aNSCLC patients (pts). The value of ALKi in the 3rd-line setting is unclear. We retrospectively assessed the real-world impact of a 3rd -line ALKi vs. non-ALKi Tx in ALK+ aNSCLC pts. Methods: Consecutive ALK+ aNSCLC pts were identified in the working databases of 7 Israeli oncology centers; pts receiving any systemic Tx beyond 2 different ALKi were selected for the comparative analysis. Pts whose immediate next Tx line (post-2nd-ALKi) was a 3rdALKi (Group (Gr) A) were compared to pts whose immediate next Tx line (post-2nd-ALKi) was non-ALKi Tx (Gr B), in terms of overall survival (OS) and time to next Tx line (TNT). Results: 158 consecutive ALK+ aNSCLC pts diagnosed in January 2011 - March 2019 were included, median follow up from diagnosis of aNSCLC was 41 months (mo) (IQR 8-45). Median OS from aNSCLC diagnosis was 56 mo (95% CI 36-66). Post-2nd-ALKi line was a 3rd ALKi for 23 pts (Gr A) and a non-ALKi Tx for 10 pts (Gr B). 7 of Gr B (70%) received ALKi as a later line Tx. Median OS after initiation of post-2nd-ALKi Tx was 27 mo (95% CI, 7-NA) for Gr A vs. 16 mo (95% CI, 7-NA) for Gr B; p-non-significant (NS) with or without adjustment for sex, age, brain metastases. TNT on post-2nd-ALKi Tx was 6 mo (95% CI, 2-27) for Gr A vs. 2.5 mo (95% CI, 0-NA) for Gr B; p-NS. Conclusions: Following progression on a 2ndALKi, OS and TNT were numerically higher for pts receiving a 3rd ALKi, but statistically NS. Extensive exposure of pts in the non-ALKi Tx Gr to an ALKi at a later stage might have impacted these results. Further studies are required to identify patients likely to benefit from ALKi after progressing on 2 or more ALKi Tx lines. [Table: see text]
Platinum-based chemotherapy (chemo) with CS1001, an anti-PD-L1 antibody, for first-line advanced non-small cell lung cancer (NSCLC): Preliminary results from phase Ib cohorts of CS1001-101 study.
Authors: Zhou Qing , Zhang Qingyuan , Xu Nong , Zhao Yanqiu , Miao Zhanhui , Shen Lin , Gao Quanli , Pei Zhidong , Xia Teddy , Wang Jingru , Dai Hangjun , Guo Rong , Yang Jianxin , Wu Yi-Long 
Published: May 2020

e21687 Background: Immuno-oncology (IO) monotherapy or combination with platinum-based chemo is the current standard of care for pts with PD-L1 expression ≥ 50% and EGFR, ALK, ROS1, BRAF negative advanced NSCLC in China. CS1001-101 phase Ib study is to evaluate the efficacy and safety of CS1001, anti-PD-L1 mAb, in pts with solid tumors or lymphomas. Here we present the results of 2 cohorts: CS1001 plus platinum-based chemo for 1L advanced NSCLC. Methods: Pts with non-squamous (nsq)-NSCLC received 4-6 cycles of CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and pemetrexed (500 mg/m2), followed by maintenance therapy with CS1001 and pemetrexed. Pts with squamous (sq)-NSCLC received CS1001 (1200 mg, IV, Q3W), carboplatin (AUC = 5), and paclitaxel (175 mg/m2), followed by maintenance therapy with CS1001. Results: By July 1st, 2019, 21 nsq-NSCLC and 20 sq-NSCLC pts were treated, with a median treatment duration of 135 and 109 days, respectively. 15 nsq-NSCLC pts remained on the study and 6 discontinued CS1001, 5 due to progressive disease (PD). 17 sq-NSCLC pts remained on the study and 3 discontinued CS1001, 2 due to adverse events (AEs). 10 had partial response (PR) in each cohort, leading to a response rate of 47.6% (nsq) and 58.8% (sq). The median duration of response (mDoR) and median progression-free survival (mPFS) were not reached (Table). In nsq-NSCLC cohort, 18 (85.7%) had CS1001-related AEs and 6 (28.6%) had G≥3 TRAEs. irAEs occurred in 5 pts with the most frequent ones being aspartate aminotransferase (AST) increased (4, ≤G2) and alanine aminotransferase (ALT) increased (3, ≤G2). 18 (90.0%) sq-NSCLC pts had CS1001-related AEs and 5 (25%) had G≥3 TRAEs. irAEs occurred in 3 pts with the most frequent ones being rash (2, ≤G2). AEs that led to CS1001 withdrawn only occurred in 2 sq-NSCLC pts, which were not related to CS1001. Conclusions: The combination of CS1001 and platinum-based chemo regimen demonstrated promising anti-tumor activity with a tolerable safety profile. The results of this study support further evaluation of CS1001 and platinum-based chemo in 1L NSCLC. Currently, a randomized phase III study (NCT03789604) of this treatment regimen in pts with chemo-naive advanced NSCLC is recruiting pts in China. Clinical trial information: NCT03312842. [Table: see text]
Anti-PD-1 antibody monotherapy or anti-PD-1 antibody combination with chemotherapy treated non-small cell lung cancer (NSCLC) patients with EGFR mutation: A retrospective analysis.
Authors: Yu Shaorong , Hu Ran , Shi Meiqi 
Published: May 2020

e21691 Background: Anti-PD-1/PD-L1 antibody has been approved as first- or second-line therapy in non-small cell lung cancer (NSCLC) patients and modified the management of patients with locally advanced or metastatic NSCLC. However, anti-PD-1 treatment shows less effective in patients with EGFR mutation than in those without driver gene mutation. To determine the activity of anti-PD-1 antibody in EGFR mutant NSCLC, we retrospectively evaluated response patterns among EGFR mutant NSCLC patients. Methods: We identified 58 patients with EGFR mutation who were treated with anti-PD-1 monotherapy or anti-PD-1 antibody combined with chemotherapy from March 2018 to December 2019. All of patients have received more than one treatment regimen including EGFR-TKI treatment. Objective response rates (ORR) were assessed using RECIST v1.1. Results: A total of 58 patients including 53 cases of lung adenocarcinoma, 4 cases of squamous cell carcinoma and 1 case of adenosquamous carcinoma were analyzed. Among them 26 patients received nivolumab treatment, 9 patients with pembrolizumab treatment, 9 patients with sintilimab treatment, 8 patients with JS001 treatment and 6 patients with camrelizumab treatment. Seven patients received anti-PD-1 monotherapy and the other 51 patients received anti-PD-1 combined chemotherapy. The main chemotherapeutic drugs contain docetaxel, pemetrexed, paclitaxel and paclitaxel-albumin. ORR was observed in 6 out of 58 (10%) patients. The disease control rate was 50% (29/58). The median PFS was 2.82 months. All six patients who achieved PR were received anti-PD-1 combined chemotherapy. Four patients died during treatment with anti-PD-1 therapy and we can’t confirm if these were due to cancer progress or immune related tumor hyperprogression. The adverse events were immune related pneumonia (two cases with grade 2 and one case with grade 3) and immune related hepatitis (one case with grade 2). Conclusions: Anti-PD-1 antibody combined chemotherapy seems showed moderate effect on NSCLC patients with EGFR mutation who have received anti-EGFR therapy.
Clinical outcomes between patients with and without RET fusions in advanced/metastatic non-small cell lung cancer in the United States.
Authors: Sireci Anthony , Hess Lisa M. , Han Yimei , Zhu Yajun Emily , Bhandari Naleen Raj , Martinez Ricardo 
Published: May 2020

e21693 Background: Fusions involving the REarranged during Transfection ( RET) gene are known oncogenic drivers in non-small cell lung cancer (NSCLC). The patient profile is distinct from a genomically-unselected population of NSCLC patients and may lead to the potentially confounded conclusion that RET fusion-positive patients have a better prognosis. This study characterized clinical outcomes in patients with RET fusion-positive NSCLC versus those without when correcting for known demographic differences. Methods: The Flatiron ClinicoGenomics Database, electronic medical record data linked to Foundation Medicine, Inc genomic test results, was used to identify individuals diagnosed with advanced or metastatic NSCLC who initiated anti-cancer systemic therapy between JAN2011 and JUN2019 in the US. Follow up data were available through JUN2019. Patients were considered RET+ if a fusion was reported and RET- if no fusion was reported. Baseline characteristics and tumor response were compared using Fisher’s exact, chi-squared or t-tests; unadjusted and adjusted COX models were used to compare progression-free survival (PFS) and overall survival (OS). Results: There were 5,807 eligible patients with NSCLC; 46 (0.8%) and 5,761 (99.2%) were RET+ and RET-, respectively. Patients with RET+ tumors were significantly younger (63 vs 67 yrs), better performance status, less likely to have smoking history (37% vs 82%), more likely to have non-squamous tumors (98% vs 76%) (all p < 0.05), and less likely to have ALK, ROS1, KRAS or BRAF alterations, which were each 0% in the RET+ group. There were no differences in total lines of therapy received; treatment regimens were comparable. In unadjusted analyses, patients with RET+ tumors had no significant differences in tumor response (p = 0.17) or PFS (p = 0.06) but significantly better OS outcomes (p = 0.005) from the start of first-line therapy. After adjusting for all available baseline covariates, survival outcomes were not significantly different between RET- and RET+ groups (PFS hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.86, 1.78, p = 0.26; OS HR = 1.53, 95% CI = 0.95, 2.44, p = 0.08). Conclusions: Patients with RET fusion-positive NSCLC have different baseline characteristics than patients without these fusions. The unadjusted differences in OS between groups appear to be driven by baseline demographic features and not the presence of the RET fusion, however further research is needed. Conclusions are limited by the rarity of RET fusions in NSCLC and subsequent small sample size.