The advantage of pemetrexed combined with platium chemotherapy treatement for advanced nonsquamous non-small-cell lung cancer (NSCLC) patients without drive oncogene.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20527-e20527
Author(s):  
Haiyan Xu ◽  
Yan Wang

e20527 Background:Platinum-based chemotherapy is the standard first-line treatment for non-squamous NSCLC patients without driver oncogene (EGFR, KRAS, and ALK mutations). However, it remains unknown that from which chemotherapy regimens can those patients get more benefit. Therefore, the study explore whether pemetrexed combined with platinum chemotherapy is superior to the other platinum-based chemotherapy regimens.Methods:We performed a retrospective study on 114 histologically or cytologically advanced IIIB-IV NSCLC patients admitted to Cancer Hospital from 1 Jan 2013 to 30 Dec 2015. The primary endpoint was the median progression free survival (PFS) and the disease control rate (DCR). And objective response was evaluated every two cycles by imaging according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). The multivariate logistic analyses were carried out by SPSS version 16.0. Results:114 patients received platinum-base doublet as first-line treatment. Among them, 59 patients underwent pemetrexed-containing regimens, and 55 patients received non-pemetrexed-containing regimens (38 patients for paclitaxel-containing regimens, 13 patients for gemcitabine-containing regimens, and 4 patients for other regimens.). The baseline characteristics between two groups were comparable ( p>0.05). The median PFS of pemetrexed-containing regimens was significantly longer compared with that of non-pemetrexed-containing regimens (7.2 months [95% CI: 5.3–9.1] vs. 4.9 months [95% CI: 3.2–6.6], p%0.05). DCR of pemetrexed-containing regimens was better than that of non-pemetrexed-containing regimens in the multivariate logistic analysis (89.8% vs.74.5%, p%0.05).Conclusions:Pemetrexed-containing regimens displayed more benefit than the other chemotherapy regimens for non-squamous NSCLC patients without driver oncogene. However, large scale perspective study is warranted in the future.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21040-e21040
Author(s):  
Qiming Wang ◽  
Xiuli Yang ◽  
Tianjiang Ma ◽  
Qiumin Yang ◽  
Chenghui Zhang ◽  
...  

e21040 Background: The anti-angiogenic drug bevacizumab combined with chemotherapy has achieved positive results in previous studies. In particular, the median progression-free survival (PFS) for EGFR-negative patients was increased to 8.3 months in the BEYOND study. Unlike bevacizumab, anlotinib is a novel multitarget tyrosine kinase inhibitor and can be conveniently orally administered. In the phase III trial ALTER 0303, anlotinib significantly improved overall survival (OS) and PFS in advanced NSCLC patients. This exploratory study aims to establish the efficacy and safety of anlotinib in combination with pemetrexed and carboplatin as first-line treatment in advanced non-squamous NSCLC. Methods: This is a multi-center, single-arm clinical trial. Adults with treatment-naive, histologically confirmed stage IIIB-IV non-squamous NSCLC, ECOG 0-1, and without known sensitizing EGFR/ALK alterations are included. Patients received anlotinib (12 mg p.o., QD, d1 to 14, 21 days per cycle) combined with pemetrexed (500 mg/m2, iv, d15-21, Q3W) + carboplatin (AUC = 5, iv, d15-21, Q3W) for 4 cycles followed by anlotinib and pemetrexed maintenance until disease progression (PD). The primary endpoint was PFS. Secondary endpoints were OS, objective response rate (ORR), disease control rate (DCR) and safety. Results: Between Mar 2019 and Dec 2020, 40 patients were enrolled in six centers and 31 of them have received at least one tumor assessment. Median age was 62 (33, 75); 66.7% male, 11.1% brain metastasis. At data cutoff (Dec 31, 2020), patients were followed up for a median of 8.26 months. Median PFS was 10.5 months (95% CI: NE, NE); ORR was 67.7% (0 CR, 21 PR), DCR was 96.8% (0 CR, 21 PR, 9 SD) and median OS was NE. The most common Grade ≥ 3 AEs were hypertension 22.2%, neutropenia 19.44%, myelosuppression 11.1%, thrombocytopenia 8.33%, leukopenia 5.56%, hand-foot syndrome 5.56% and there were no Grade 5 toxicities. Conclusions: This study finds that anlotinib plus pemetrexed and carboplatin can significantly improve PFS and ORR compared to standard chemotherapy for treatment-naive non-squamous NSCLC patients. The combination was well tolerated, and the AEs were manageable. The follow-up time is not sufficient, and the OS outcomes need further evaluation. Clinical trial information: NCT03790228.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8066-8066
Author(s):  
Alessandro Morabito ◽  
Vittorio Gebbia ◽  
Saverio Cinieri ◽  
Maria Grazia Viganò ◽  
Roberto Bianco ◽  
...  

8066 Background: Platinum-based chemotherapy (CT) is the standard treatment for patients (pts) with advanced NSCLC, but the evidence of its efficacy among ECOG PS2 pts is weak, because these pts are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard CT in these pts. No prospective randomized trial has tested the addition of cisplatin to single-agent CT in pts with advanced NSCLC and PS2. Methods: CAPPA-2 was a multicentre, randomized phase III study for first-line treatment of PS2 pts with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI ed.) and adequate organ function. Patients in standard arm received gemcitabine 1,200 mg/m2 dd1 and 8.Patients in experimental arm received cispaltin 60 mg/m2 d1 plus gemcitabine 1,000 mg/m2 dd1 and 8. All treatments were repeated q3w, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. Results: The study was stopped in June 2012 after the enrolment of 57 pts, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin + gemcitabine (HR 0.52, 95% CI 0.28-0.98, p=0.039). Combination CT produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p=0.017) and higher response rate (4% vs. 18%, p=0.19), without substantial increase in toxicity. Conclusions: Addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC. Clinical trial information: NCT00526643.


2021 ◽  
Vol 20 ◽  
pp. 153303382110623
Author(s):  
Hongsik Kim ◽  
Hana Kim ◽  
Ryul Kim ◽  
Hyunji Jo ◽  
Hye Ryeon Kim ◽  
...  

Background: High tumor mutational burden (TMB-H) has been reported as a predictive marker to immunotherapy or prognostic marker in various tumor types. However, there has been little study of the role of TMB-H in advanced biliary tract cancer (BTC). Methods: We analyzed 119 advanced BTC patients who received Gemcitabine/Cisplatin (GP) as a first-line treatment between November 2019 and April 2021. Next-generation sequencing (NGS), including TMB analysis, as a routine clinical practice was performed in 119 patients. The TruSightTM Oncology 500 assay from Illumina was used as a cancer panel. Results: Among 119 patients, 18 (18.5%) had a tumor with high TMB (≥ 10 Muts/Mb). There were no significant differences between the status of TMB and clinical outcomes with GP, including objective response rate (ORR) ( P = .126), disease control rate (DCR) ( p = .454), and median progression-free survival (PFS) ( p = .599). The median overall survival (OS) was not different between patients with TMB-H and no TMB-H ( p = .430). In subgroup analysis of 32 patients receiving immune checkpoint inhibitor (ICIs), there were significant differences in ORR ( p = .034) and median PFS ( p  = .025) with ICIs between patients with and without TMB-H. Conclusions: This study revealed that TMB-H in advanced BTCs did not have a prognostic or role in the standard first-line treatment. However, TMB-H might be a predictive biomarker for response to ICIs in advanced BTC.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5024-5024 ◽  
Author(s):  
R. J. Motzer ◽  
R. A. Figlin ◽  
T. E. Hutson ◽  
P. Tomczak ◽  
R. M. Bukowski ◽  
...  

5024 Background: In a randomized phase III trial of patients (pts) with mRCC, sunitinib demonstrated a significant improvement in progression-free survival (PFS) and objective response rate (ORR) compared to IFN-a as first-line therapy (Proc ASCO 2006;24:2s [Abstract LBA3]). We present the most recent data from this trial and an analysis of prognostic factors. Methods: Untreated pts with clear-cell mRCC were randomized 1:1 to receive either sunitinib (repeated 6-week cycles of 50 mg/day orally for 4 weeks, followed by 2 weeks off treatment) or IFN-a (9 MU given subcutaneously three times weekly). The primary endpoint was PFS. Results: A total of 750 pts were randomized: 375 to sunitinib, 375 to IFN-a. The median duration of treatment is 11 months (range: <1–25) for sunitinib vs. 4 months (range: <1–22) for IFN-a. The updated ORR by investigator assessment is 44% (95% CI: 39, 49) for sunitinib vs. 11% (95% CI: 8, 15) for IFN-a (p <0.000001), including 4 complete responses for sunitinib and 2 for IFN-a. The median duration of response in the sunitinib group (n=165) is 12 months (95% CI: 10, 14) vs. 10 months (95% CI: 8, 17) in the IFN-a group (n=43). The median PFS is 11 months (95% CI: 10, 11) for sunitinib vs. 4 months (95% CI: 4, 5) for IFN-a. The median PFS for pts with 0 risk factors is 14 months (95% CI: 11, 16) for sunitinib vs. 8 months (95% CI: 7, 10) for IFN-a; 9 months (95% CI: 8, 11) vs. 4 months (95% CI: 4, 4), respectively, for pts with 1- 2 risk factors; 4 months (95% CI: 2, 10) vs. 1 month (95% CI: 1, 2), respectively, for pts with =3 risk factors. The sunitinib benefit in PFS extends across all MSKCC prognostic risk factor groups (HR=0.488; 95% CI: 0.406, 0.586). The baseline features that predict longer PFS (by investigator assessment) for the sunitinib group are hemoglobin =LLN (p=0.0043), corrected calcium =10 mg/dL (p=0.001), ECOG score of 0 (p=0.0005), number of metastatic sites 0 or 1 (p=0.0064), and time from diagnosis to treatment =1 yr (p=0.0002). Conclusions: Sunitinib is a reference standard for first-line treatment of mRCC, with significant improvement in PFS and ORR compared to IFN-a. The benefit of sunitinib extends across all subgroups of pts with mRCC. Previously defined MSKCC risk factors for mRCC predict longer PFS with sunitinib. No significant financial relationships to disclose.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19054-e19054 ◽  
Author(s):  
Toshiyuki Kozuki ◽  
Naoyuki Nogami ◽  
Hiromoto Kitajima ◽  
Tetsu Shinkai ◽  
Fumiaki Kato ◽  
...  

e19054 Background: The addition of BV to cytotoxic agent(s) prolonged survival for non-Sq NSCLC patients (pts). However, there is no definitive evidence for the cytotoxic agent(s) plus BV is superior to the cytotoxic agent(s) alone for elderly non-Sq NSCLC. We conducted the feasibility study of PEM plus BV as the first-line treatment for elderly advanced or recurrent non-Sq NSCLC. Methods: Major eligibility and exclusion criteria were followings; chemotherapy-naïve; unfit for bolus combination chemotherapy; stage III/IV or relapsed non-Sq NSCLC; age≥70; PS 0-1; no evidence of brain metastasis; no history of hemoptysis and irradiation for thorax. PEM (500 mg/m2) and BV (15 mg/kg) were administrated intravenously on day 1 every 3 weeks. The primary endpoint was toxicity and the secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the percentage of pts who completed more than 3 cycles. Results: From November 2010 to April 2012, total 12 pts were enrolled. Patients characteristics were following; male/female=6/6; Median age (range) 78 (72-81); histology was all adenocarcinoma; activating EGFR mutation no/yes/unknown=9/2/1; stage IIIB/IV/recurrence=2/8/2; ECOG PS 0/1=6/6; smoking history yes/no=6/6. Severe toxicities (Grade 3≥) were leukopenia (25%), neutropenia (25%), anemia (8%), thrombocytopenia (8%), febrile neutropenia (8%), anorexia (8%), hypertension (8%), fatigue (8%), nausea (8%), and perforation (colon) (8%). No dose-limiting toxicity and treatment-related death was occurred. Three patients achieved PR and the ORR was 25%. The median PFS and OS were 5.6 months (mo) (95% C.I. 1.1-7.9 mo) and 10.3 mo (95% C.I. 6.9-15.6 mo) in 11 evaluated pts, respectively. The 1-year survival rate was 49% (95% C.I. 12-79%). Seven of 12 pts (58%) received more than 3 cycles. Conclusions: PEM plus BV as first-line treatment for elderly non-Sq NSCLC was well tolerable and promising. Clinical trial information: UMIN000004263.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 328-328
Author(s):  
Takayuki Ando ◽  
Ayumu Hosokawa ◽  
Hiroki Yoshita ◽  
Akira Ueda ◽  
Shinya Kajiura ◽  
...  

328 Background: Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, because studies on salvage chemotherapy are limited, its role remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods: Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2006 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results: Eight males and two females ((median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. A total of 30 cycles of amrubicin was administered in 10 patients, with a median number of cycles per patients was 2.5 (range, 1-7). Median progression-free survival (PFS) and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Two patients with partial response had characteristics of NEC with a high Ki-67 index (99% and 89%, respectively) and had received cisplatin and irinotecan as first-line treatment. Grade 3–4 neutropenia and anemia were observed in four (40%) and five (50%) patients, and they were manageable in all cases by careful monitoring of myelosuppression and appropriate dose reduction of amrubicin. Conclusions: Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15018-e15018
Author(s):  
Mingyi Zhou ◽  
Ping Yu ◽  
Dengue Hernick ◽  
Yanrong Li ◽  
Yuanhe Wang ◽  
...  

e15018 Background: Controversy surrounds the question of whether the prognosis of most patients with metastatic colorectal cancer (mCRC) is improved using intensive administration of folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) alone or combined with target therapy as first-line treatment. Methods: We queried PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials, Cochrane Systematic Reviews, ClinicalTrials.gov, the databases of the European Society for Medical Oncology and the American Society of Clinical Oncology to identify abstracts of randomized controlled trials evaluating the efficacies and toxicities of intensive therapies used for first-line treatment of patients with mCRC. The search included articles dated from the inception of these resources until December 31, 2016. We estimated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and relative risks (RRs) for the objective response rate (ORR), the R0 resection rate, and toxicities. Results: Nine RCTs comprising 2,256 patients were included in this network meta-analysis. The PFS of patients administered FOLFOXIRI plus target therapy experienced prolonged PFS and OS and improved ORRs compared with FOLFOX or FOLFIRI plus target therapy (PFS: HR 0.65, 95% CI 0.46–0.91; OS: HR 0.80, 95% CI 0.65–0.98; ORR: HR 1.70, 95% CI 1.16–2.49; R0 resection rate: HR 2.66, 95% CI 1.86–3.82). There were no significant differences between PFS, OS, ORRs, or R0 resection rates and toxicities of patients administered FOLFOXIRI and FOLFOX or FOLFIRI plus target therapy. Further, FOLFOXIRI plus target therapy did not increase toxicities compared with FOLFOX or FOLFIRI plus target therapy, except for neutropenia. Conclusions: FOLFOXIRI plus target therapy when administered as first-line treatment of patients with mCRC is the best choice and did not significantly increase toxicities. FOLFOXIRI is as effective as FOLFOX or FOLFIRI plus target therapy.


2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 710-710
Author(s):  
Dusan Kotasek ◽  
Adnan Nagrial ◽  
Sumit Lumba ◽  
Niall C. Tebbutt ◽  
Thomas J. George ◽  
...  

710 Background: SBP-101, a polyamine metabolic inhibitor, inhibited growth in 6 human pancreatic ductal adenocarcinoma (PDA) cell lines and 3 murine xenograft tumor models of human PDA. SBP-101 monotherapy in heavily pre-treated PDA patients (> 2 prior regimens, N=4) showed a median survival of 5.9 months at the optimal dose level. Purpose: To assess the safety, tolerability, PK, and efficacy of SBP-101 in combination with gemcitabine (G) and nab-paclitaxel (A) in patients with previously untreated metastatic PDA. Methods: In a modified 3+3 dose escalation scheme, subcutaneous injections of SBP-101 were dosed at 0.2, 0.4 or 0.6 mg/kg days 1-5 of each 28-day cycle. G (1000 mg/m2) and A (125 mg/m2) were administered intravenously on Days 1, 8, and 15 of each cycle. Safety and tolerability were evaluated by clinical and laboratory assessments. PK was evaluated on day 1 of cycle 1. Efficacy was assessed by CA19-9 levels, objective response as assessed by RECIST criteria, progression-free survival (PFS) and overall survival (OS). Results: Fifteen patients have been enrolled in 3 cohorts (1: N=4, 2: N=7, 3: N=4) and received up to 6 cycles of treatment (7 subjects are ongoing in cohorts 2 and 3). The most common adverse events related to SBP-101 are fatigue (N=4), nausea (N=2) and injection site pain (N=2). There is no evidence of SBP-101-related bone marrow suppression or peripheral neuropathy. One patient in cohort 2 developed grade 3-4 reversible liver enzyme elevation. PK parameters in cohort 1 were below the limits of detection at most time points, but plasma Cmax and AUC0-t were measurable in cohorts 2 and 3. In those cohorts, CA19-9 levels decreased 76-95% in 7 of 8 evaluable subjects (1 additional subject TBD), with 5 patients achieving partial responses (4 ongoing) and 1 achieving stable disease. Median PFS and OS have not yet been reached. Conclusions: Preliminary results suggest SBP-101 is well tolerated when administered with G and A. Signals of efficacy support continued development of SBP-101 in combination first-line treatment for PDA. Clinical trial information: NCT03412799.


2013 ◽  
Vol 2013 ◽  
pp. 1-6
Author(s):  
Ying Liu ◽  
Zhengbao Ye ◽  
Wenqi Xi ◽  
Tao Ma ◽  
Min Shi ◽  
...  

Objective.To evaluate the efficacy and safety of docetaxel plus oxaliplatin and capecitabine (DOX) in the first line treatment of advanced gastric adenocarcinoma.Methods.A total of 37 patients were enrolled into this study, and they received DOX regimen (docetaxel 75 mg/m2and oxaliplatin 130 mg/m2intravenous infusion on day 1, and capecitabine 1000 mg/m2orally twice daily on d1–14); treatment was repeated every 3 weeks.Results.All 37 patients were assessable for evaluation. The numbers of patients with complete response (CR), partial responses (PR), stable disease (SD), and progressive disease (PD) were 1, 10, 23, and 3, respectively. The objective response rate (ORR) was 29.7%, with the disease control rate (DCR) of 91.9%. Median progression-free survival (mPFS) and overall survival (mOS) were 197 days and 364 days, respectively. The most common grade 3/4 toxicities were hematological toxicities. The most common grade 3/4 nonhematological toxicities were fatigue, nausea, vomiting, anorexia, diarrhea, and hand-foot syndrome.Conclusion.The DOX regimen demonstrated a promising efficacy as the first line regimen in treating advanced gastric cancer patients with good performance status, the toxicities were tolerated and controllable. Large-scale clinical observation is necessary to get further evidence.


Sign in / Sign up

Export Citation Format

Share Document