bluuebunny/crossref_metadata_2025_split huggingface dataset:
Carboplatin versus cisplatin for the treatment of extensive-stage small cell lung cancer (SCLC): A National VA Database analysis.
Authors: Azar Ibrahim , Austin Adam , Kim Seongho , Jang Hyejeong , Chopra Amit , Mehdi Syed Arzoo , Mamdani Hirva 
Published: May 2020

9061 Background: Current standard of care first line treatment for extensive stage SCLC includes combination of platinum-etoposide doublet with an immune checkpoint inhibitor. Carboplatin is preferred over cisplatin in the extensive stage disease because of its favorable toxicity profile. Data comparing the efficacy of carboplatin with cisplatin in the metastatic setting are limited. Methods: Data from the National VA Cancer Cube database were compiled. Only pathologically confirmed cases of extensive stage SCLC that received platinum-based multiagent chemotherapy were included. Interval-censored Weibull and Cox proportional hazard regression models were used to estimate median overall survival (OS) and hazard ratio (HR), respectively. Two survival curves were compared by a Wald test. Results: Overall, 2600 SCLC cases were studied: 1968 received carboplatin-based therapy (Carbo-SCLC) while 632 received cisplatin-based therapy (Cis-SCLC). Median OS of Carbo-SCLC and Cis-SCLC was 0.71 years (95% CI 0.68-0.75) versus 0.70 years (95% CI 0.64-0.76), respectively (HR = 0.99; 95% CI 0.90-1.10; p = 0.90). Median OS of patients with ECOG-PS of 0, 1, 2 and 3 was similar for Carbo-SCLC and Cis-SCLC. HR of death for Carbo-SCLC compared to Cis-SCLC stratified by performance status were: ECOG-PS 0: 1.04 (95% CI 0.78-1.38; p = 0.80); ECOG-PS 1: 0.87 (95% CI 0.71-1.06; p = 0.17); ECOG-PS 2: 0.92 (95% CI 0.69-1.24; p = 0.6); ECOG- PS 3: 1.13 (95% CI 0.66-1.92; p = 0.66). Multivariable regression analysis accounting for age and ECOG-PS shows a HR of 0.92 (95% CI 0.80-1.05; p = 0.24). Conclusions: Cisplatin-based chemotherapy was not associated with a survival advantage over carboplatin-based chemotherapy in extensive-stage SCLC., including in patients with robust performance status and young patients. The findings from this large dataset along with the favorable toxicity profile of carboplatin support its use as the platinum agent of choice in extensive stage SCLC.
Treatment strategies for thymic carcinoma in a real-life setting: Insights from the rythmic network.
Authors: Girard Nicolas , Petat Arthur , Dansin Eric , Fabien Calcagno , Greillier Laurent , Pichon Eric , Kerjouan Mallorie , Clément Duchene Christelle , Mennecier Bertrand , Westeel Virginie , Thillays Francois , Quantin Xavier , Ginoux Marylise , Oulkhouir Youssef , Thiberville Luc , Ricordel Charles , Molina Thierry , Fournel Pierre , Bigay-Game Laurence , Besse Benjamin 
Published: May 2020

9072 Background: Thymic carcinomas are an aggressive and difficult to treat subset of thymic epithelial tumors (TETs) that represent a heterogeneous group of rare intrathoracic malignancies. Most of the current knowledge and guidelines tumors rely on surgically-oriented databases focusing on early-stage disease, and small prospective, single-arm trials conducted in metastatic thymic carcinomas, mostly in a refractory, late-line setting. “Réseau tumeurs THYMiques et Cancer” (RYTHMIC) is the nationwide network for TETs in France. The management of any patient has to be systematically discussed on a real-time basis at a national multidisciplinary tumor board; a database is hosted by the French Thoracic Cancer Intergroup (IFCT). Methods: We took advantage of the RYTHMIC prospective database to describe baseline characteristics, analyze treatment strategies, and provide landmark outcomes in a cohort of consecutive patients with thymic carcinoma. The inclusion period was January 2012 to April 2017. Results: A total of 213 patients were analyzed. Overall, 60 (28%) patients were considered as surgical candidates upfront, 91 (43%) received primary chemotherapy, and 62 (29%) received exclusive chemotherapy. Median OS was 49.2 months (IC95%: 34.8-63.6); OS was significantly longer in patients with a lower stage at diagnosis (p < 0.001), who were operated on upfront, as opposed to patients who received primary or exclusive chemotherapy (p < 0.001). Surgery, conducted upfront or after primary chemotherapy, was significantly associated with more prolonged OS (p < 0.001); complete resection and postoperative radiotherapy were also predictors of better outcome (p = 0.018 and p = 0.081, respectively). Exclusive chemotherapy was delivered to 62 patients with advanced disease, who all received platinum-based regimen as first-line treatment; PAC regimen was delivered to 66% of patients. Best objective response to first-line chemotherapy was partial response in 33 (53%) patients. Median PFS was 8.0 months (IC95%: 5.0-11.1). Median OS was 32.9 months (IC95%: 20.6-45.1). Response to first-line chemotherapy and squamous histology were the only significant predictors of OS (p = 0.002 and p = 0.040, respectively). Conclusions: Our cohort is the first to analyze in depth outcomes and treatment strategies in a prospective cohort of consecutive patients with thymic carcinoma. While we confirm the major prognostic impact of surgery, our data highlight the need for optimized multidisciplinary management and innovative therapies as the survival of patients remains limited.
Primary analysis of a randomized, double-blind, phase II study of the anti-TIGIT antibody tiragolumab (tira) plus atezolizumab (atezo) versus placebo plus atezo as first-line (1L) treatment in patients with PD-L1-selected NSCLC (CITYSCAPE).
Authors: Rodriguez-Abreu Delvys , Johnson Melissa Lynne , Hussein Maen A. , Cobo Manuel , Patel Anjan Jayantilal , Secen Nevena Milica , Lee Ki Hyeong , Massuti Bartomeu , Hiret Sandrine , Yang James Chih-Hsin , Barlesi Fabrice , Lee Dae Ho , Paz-Ares Luis G. , Hsieh Robert Wenchen , Miller Karen , Patil Namrata , Twomey Patrick , Kapp Amy V. , Meng Raymond , Cho Byoung Chul 
Published: May 2020

9503 Background: The immunomodulatory receptor TIGIT is a novel inhibitory immune checkpoint present on activated T cells and NK cells in multiple cancers, including NSCLC. In a phase I study (GO30103), co-inhibition of TIGIT and PD-L1 signaling with tira plus atezo in CIT-naïve PD-L1 positive NSCLC potentially improved overall response rates (ORR) compared to historical ORR with PD-L1/PD-1 inhibitors. We conducted this phase II trial to confirm the efficacy and safety of tira plus atezo (TA) compared to placebo plus atezo (PA) in 1L NSCLC (GO40290, NCT NCT03563716). Methods: This prospective, randomized, double-blind, placebo-controlled trial enrolled patients (pts) with chemotherapy-naïve PD-L1+ (TPS ≥ 1% by 22C3 IHC pharmDx Dako assay) locally advanced or metastatic NSCLC with measurable disease, ECOG PS 0-1, and without EGFR or ALK alterations. Pts were randomized 1:1 to TA (tira 600 mg IV plus atezo 1200 mg IV) or PA (placebo plus atezo 1200 mg IV) on day 1 of every 3-week cycle. Stratification factors were PD-L1 status (TPS ≥ 50% vs TPS 1-49%), histology, and tobacco history. Co-primary endpoints were investigator assessed ORR and PFS, and additional endpoints were duration of response (DOR), OS, and safety. Exploratory endpoints were the effect of PD-L1 status on ORR and PFS. Results: 135 pts were randomized to PA (n = 68) or TA (n = 67). At primary analysis (30 Jun 2019), TA improved ORR and median PFS (mPFS) compared to PA, with median follow-up of 5.9 mo. In the safety population (68 in PA, 67 in TA), treatment-related AEs (TRAEs) occurred in 72% (PA) and 80.6% (TA); Grade ≥3 TRAEs occurred in 19.1% (PA) and 14.9% (TA). AEs leading to treatment withdrawal occurred in 10.3% (PA) and 7.5% (TA). Clinical trial information: NCT03563716 . With an additional six months of follow-up since the primary analysis (2 Dec 2019, median follow-up of 10.9 mo), improvement in ORR and mPFS was maintained in ITT for TA (37.3% [25.0, 49.6] and 5.6 mo [4.2, 10.4]) vs PA (20.6% [10.2, 30.9] and 3.9 mo [2.7, 4.5]). The safety profile remained tolerable. Conclusions: Treatment with TA compared to PA showed clinically meaningful improvement in ORR and PFS in ITT. The safety profile of TA was similar to PA. [Table: see text]
Concurrent osimertinib plus gefitinib for first-line treatment of EGFR-mutated non-small cell lung cancer (NSCLC).
Authors: Rotow Julia K , Costa Daniel Botelho , Paweletz Cloud P. , Awad Mark M. , Marcoux Paul , Rangachari Deepa , Barbie David Allen , Sands Jacob , Cheng Michael L. , Johnson Bruce E. , Oxnard Geoffrey R. , Jackman David Michael , Kwiatkowski David J. , Kehl Kenneth L. , Izdebski Monika D , Lau Christie J. , Vasquez Kevin A , Janne Pasi A. 
Published: May 2020

9507 Background: First-line treatment with an EGFR tyrosine kinase inhibitor (TKI) is standard of care for patients (pts) with EGFR-mutated NSCLC. The EGFR TKI osimertinib is active against the acquired gefitinib-resistant mutation EGFR T790M, as is gefitinib against the osimertinib-resistant EGFR C797S. Preclinical evidence suggests dual EGFR inhibition with gefitinib + osimertinib may delay emergence of acquired resistance. Methods: This ongoing phase I/II study enrolled pts with stage IV EGFR-mutated (L858R or del19) NSCLC, without prior therapy for metastatic disease. Treatment in dose escalation (n = 6): concurrent osimertinib 40 mg or 80 mg + gefitinib 250 mg daily. In dose expansion (n = 21): osimertinib + gefitinib at the maximum tolerated dose (MTD). Prior to protocol amendment 6 pts received alternating monthly cycles of TKI monotherapy and were excluded from this analysis. The primary endpoints in the dose escalation and expansion phases were, respectively, identification of the MTD and feasibility, defined as receipt of combination therapy for ≥ 6 four-week cycles. Secondary endpoints included overall response rate (ORR), survival outcomes, plasma EGFR mutation clearance (cell free DNA by droplet digital PCR (ddPCR)), and mechanisms of acquired resistance. Results: From May 2017 to July 2019 27 pts were enrolled and evaluable for the primary endpoints. The MTD was osimertinib 80 mg plus gefitinib 250 mg orally daily. In feasibility analysis, 81.5% completed ≥6 cycles combination therapy (1 pt discontinued for progression, 4 for toxicity). The ORR was 85.2% (95% CI 67.5%-94.1%). Best response: 85.2% partial response, 14.8% stable disease. The most common treatment-related adverse effects (TRAEs) (% any grade, % grade 3) were rash (96.3%, 3.7%), diarrhea (85.2%, 11.1%) and dry skin (70.4%, 0%). Plasma ddPCR (n = 25 pts) detected the driver EGFR mutation at baseline in 68% of pts. In these pts, plasma EGFR cleared to undetectable at 2 weeks treatment in 82.4%. At 14.8 months median follow up the median progression free survival was not yet reached. Conclusions: Combination therapy with osimertinib and gefitinib is tolerable for first-line treatment of EGFR-mutated NSCLC and resulted in rapid plasma clearance of the EGFR mutation. The observed ORR is consistent with previously reported first-line response rates to osimertinib. Analysis of survival outcomes and acquired resistance mechanisms are pending data maturity and will facilitate understanding of the role of first-line dual EGFR TKI therapy for this pt population. Clinical trial information: NCT03122717 .
Capmatinib in patients with high-level MET-amplified advanced non–small cell lung cancer (NSCLC): results from the phase 2 GEOMETRY mono-1 study.
Authors: Wolf Juergen , Overbeck Tobias R. , Han Ji-Youn , Hochmair Maximilian , de Marinis Filippo , Ohashi Kadoaki , Smit Egbert F. , Power Danielle , Garon Edward B. , Groen Harry J.M. , Tan Daniel Shao-Weng , Waldron-Lynch Maeve , Le Mouhaer Sylvie , Nwana Ngozi , Giovannini Monica , Heist Rebecca Suk 
Published: May 2020

9509 Background: In the ongoing, multicohort, phase 2 GEOMETRY mono-1 study, capmatinib (INC280) has shown efficacy in METex14–mutated NSCLC patients (pts) who were pretreated (cohort 4) or treatment (tx)-naïve (cohort 5b). Here, we report the efficacy and safety of capmatinib in pts with high-level MET-amplified (gene copy number [GCN] ≥10) advanced NSCLC who were either pretreated with 1 or 2 prior lines of systemic therapy (cohort 1a) or tx-naïve (cohort 5a). Methods: Adult pts (≥18 years), ECOG PS 0–1 who had ALK and EGFR wt, stage IIIB/IV (any histology) MET-amplified NSCLC with GCN≥10 received capmatinib 400 mg twice daily (fasting). Primary and key secondary endpoints were overall response rate (ORR) and duration of response (DOR), respectively, by blinded independent review committee (BIRC) assessment per RECIST v1.1. Other secondary endpoints included investigator-assessed ORR, DOR, disease control rate (DCR), progression-free survival (PFS, BIRC and investigator assessment), overall survival, and safety. Results: As of Jan 06, 2020, 84 pts were evaluable for efficacy (cohort 1a [2nd/3rd line], 69 pts; Cohort 5a [1st line], 15 pts). Tx was ongoing for 3 pts in cohort 1a, none in cohort 5a. Per BIRC assessment in cohorts 1a and 5a, respectively, ORR was 29% and 40%, median DOR was 8.31 months (mo, 20 responders, 95% CI: 4.17–15.44) and 7.54 mo (6 responders, 95% CI: 2.56–14.26), and median PFS was 4.07 (95% CI: 2.86–4.83) and 4.17 (95% CI: 1.45–6.87) mo. Investigator assessment was in line with BIRC assessment (Table). The most common adverse events across all cohorts (≥25%, all grades, N = 364) were peripheral edema (51.1%), nausea (44.8%) and vomiting (28.0%). Data for biomarker analysis and pts with brain metastasis will be presented at the ASCO 2020 meeting. Conclusion: Capmatinib has demonstrated activity in the subset of pts with high-level MET-amplified (GCN≥10) NSCLC, with a higher response rate in tx-naïve pts. Safety profile remains favorable and similar to previous reports of capmatinib. Clinical trial information: NCT02414139 . [Table: see text]
Poziotinib shows activity and durability of responses in subgroups of previously treated EGFR exon 20 NSCLC patients.
Authors: Le Xiuning , Goldman Jonathan Wade , Clarke Jeffrey Melson , Tchekmedyian Nishan , Piotrowska Zofia , Chu David , Bhat Gajanan , Lebel Francois M. , Socinski Mark A. 
Published: May 2020

9514 Background: Treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 mutations is an unmet medical need. Poziotinib is a potent tyrosine kinase inhibitor (TKI) of EGFR and HER2 exon 20 insertion mutants. We evaluated the efficacy and safety of poziotinib in previously treated NSCLC patients with EGFR exon 20 insertion mutations in an independent cohort of a multi-cohort, multi-center Phase 2 study ( ZENITH20-1). Methods: ZENITH20-1 study enrolled pts with advanced NSCLC with an EGFR exon 20 insertion identified on local tissue testing who had received at least one prior line of therapy. Poziotinib (16 mg) was administered orally QD, allowing dose reductions for AEs, with follow up for 24 months. The primary endpoint was objective response rate (ORR), evaluated centrally by RECIST v1.1. Secondary endpoints included disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and safety. Efficacy was also evaluated by specific exon 20 insertions and prior lines of therapy. Results: 115 patients with a median age of 61 years (33-83) were enrolled. Patients had a median of 2 prior lines of therapy (range, 1-9.) The median relative dose intensity was 72% (7-100%) with 65% having dose reductions. The ORR in the as-treated population was 14.8% (95% CI 8.9 - 22.6%), and the DCR was 68.7% (95% CI 59.4 - 77.0%) with a median DoR of 7.4 months. 65% patients had tumor size reductions and the median PFS was 4.2 months. In the evaluable population (n = 88), the ORR was 19.3% and the unconfirmed ORR was 25%. Responses were predominantly observed in insertions between residues M766 to D770 of exon 20 (8/44; 18.2%). Responses were observed in patients with 2 lines (14%); ≥3 lines of therapy (16.2%). The most common treatment-related Grade ≥3 AEs were rash (28%), diarrhea (26%), stomatitis (9%) and paronychia (6%). The incidence of treatment-related pneumonitis was 4%, however some cases may have been confounded by prior checkpoint inhibitors as first line treatment. Conclusions: Although the ORR primary endpoint was not met, poziotinib induced tumor reduction in the majority of patients with durable responses, including the heavily pre-treated population. Responses were more common in patients with insertions between M766 to D770 of EGFR exon 20. The safety profile was overall consistent with other 2nd generation EGFR TKIs. Evaluation of these subgroups with refined dosing and improved toxicity management to maintain continuous treatment is warranted to assess the potential of poziotinib in Exon20 related tumors. Clinical trial information: NCT03318939 .
Updated overall survival (OS) and safety data from the randomized, phase III ALEX study of alectinib (ALC) versus crizotinib (CRZ) in untreated advanced ALK+ NSCLC.
Authors: Peters Solange , Mok Tony S. K. , Gadgeel Shirish M. , Rosell Rafael , Dziadziuszko Rafal , Kim Dong-Wan , Perol Maurice , Ou Sai-Hong Ignatius , Shaw Alice Tsang , Bordogna Walter , Smoljanovic Vlatka , Hilton Magalie , Ruf Thorsten , Archer Venice Rosale , Camidge D. Ross 
Published: May 2020

9518 Background: Final, mature PFS from the global phase III ALEX study (NCT02075840) of ALC vs CRZ in untreated, advanced/metastatic ALK+ NSCLC have been previously published: ALC 34.8 months (m) (95% CI 17.7–NR) vs CRZ 10.9 m (95% CI 9.1–12.9), (HR 0.43, 95% CI 0.32–0.58). We report 5-year OS and updated safety data from ALEX with a further 12 m follow-up (FU) (cutoff date: Nov 29, 2019). Methods: Patients (pts) with stage IIIB/IV ALK+ NSCLC (by central IHC), ECOG PS 0–2 and no prior systemic therapy for advanced NSCLC were randomized 1:1 to ALC 600 mg BID (n = 152) or CRZ 250 mg BID (n = 151). Asymptomatic CNS metastases (mets) at baseline (BL) were allowed. OS was a secondary endpoint, and no formal statistical testing was planned. Results: Median duration of FU: 48.2 m with ALC vs 23.3 m with CRZ. OS data remain immature (events: 37%; stratified HR 0.67 [95% CI 0.46–0.98]); median OS with CRZ was 57.4 m (95% CI 34.6–not estimable [NE]) vs NE with ALC. The 5-year survival rate was 62.5% (95% CI 54.3–70.8) with ALC vs 45.5% (95% CI 33.6–57.4) with CRZ (Table). In pts with CNS mets at BL the OS HR was 0.58 (95% CI 0.34–1.00) and 0.76 (95% CI 0.45–1.26) in pts without CNS mets at BL. The OS benefit of ALC vs CRZ was generally consistent across all subgroups. Considering the longer treatment duration for ALC (28.1 m) vs the previous analysis (27.7 m), the safety profile of ALC remains consistent; no new safety signals were observed. With ALC, 35% of pts remain on study treatment vs 9% of pts remaining on CRZ. In pts with ≥1 known post-progression treatment (ALC: 32.2%; CRZ: 45.7%), lorlatinib was the most common ALK TKI received after first-line ALC (7.2%), compared with ceritinib after first-line CRZ (15.2%). Conclusions: This is the first global randomized study of a 2nd generation ALK TKI to demonstrate a clinically meaningful improvement in OS vs CRZ in ALK+ NSCLC (5-year survival rate: 62.5%, ALC vs 45.5%, CRZ); longer FU is required as OS data remain immature. Clinical trial information: NCT02075840 . [Table: see text]
Phase II study of savolitinib in patients (pts) with pulmonary sarcomatoid carcinoma (PSC) and other types of non-small cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations (METex14+).
Authors: Lu Shun , Fang Jian , Li Xingya , Cao Lejie , Zhou Jianying , Guo Qisen , Liang Zongan , Cheng Ying , Jiang Liyan , Yang Nong , Han Zhigang , Shi Jianhua , Chen Yuan , Xu Hua , Zhang Helong , Zhang Di , Li Jing , Wang Linfang , Ren Yongxin , Su Weiguo 
Published: May 2020

9519 Background: There are unmet medical needs for pts with METex14+ NSCLC. PSC is a rare type of NSCLC with high incidence of MET exon 14 mutations and poor prognosis. Savolitinib (AZD6094, HMPL-504, volitinib) is a highly selective oral MET tyrosine kinase inhibitor, and its anti-tumor activity has been shown in combination with osimertinib in pts with EGFR-mutant, MET-amplified NSCLC (Yu H, et al. 2019 AACR, Abstract CT032). Methods: This was a multicenter, multi-cohort, single-arm phase II study (NCT02897479) to evaluate the efficacy, safety, and pharmacokinetics of savolitinib in pts with unresectable or metastatic METex14+ PSC and other NSCLC. MET mutation was tested or retrospectively confirmed by central laboratory. Savolitinib was taken orally, once daily (QD) (600mg for weight ≥50kg or 400mg weight < 50kg) until disease progression or intolerable toxicity. Tumor was evaluated every 6 weeks during the 1st year and every 12 weeks thereafter. The primary endpoint was independent review committee (IRC) assessed objective response rate (ORR) (RECIST version 1.1). Here we report the results of one cohort of prior MET-treatment naïve patients. Results: As of October 31, 2019, 593 pts were pre-screened/screened, 87 identified with METex14+ and 70 treated. Among treated pts, median age was 68.7 years (range 51.7-85.0), 58.6% pts were male, 92.9% stage IV, 60.0% previously treated, 57.1% with adenocarcinoma, 35.7% with PSC and the rest with other pathological types. Sixty-one pts were efficacy evaluable by IRC assessment (N = 61) (including pts who had at least one measurable lesion at baseline and had ≥1 scheduled post-baseline tumor assessment or evidence of any post-baseline radiological disease progression): ORR was 47.5% (95% CI: 34.6%, 60.7%), disease control rate 93.4% (95% CI: 84.1%, 98.2%) and median duration of response not reached yet. The median progression-free survival was 6.8 months (95% CI 4.2, 13.8) among all treated pts. Efficacy results were consistent with investigators’assessments. The most common (≥20%) treatment-related adverse events (TRAEs) were peripheral edema, nausea, increased AST/ALT, vomiting and hypoalbuminemia. The incidence of ≥ grade 3 TRAEs was 41.4%. TRAEs leading to treatment discontinuation occurred in 14.3% pts, among which liver injury and hypersensitivity were most common (each 2.9%). Conclusions: Savolitinib demonstrated promising anti-tumor activity and acceptable tolerability in METex14+ NSCLC pts. Clinical trial information: NCT02897479 .