Paclitaxel Plus Gemcitabine Research Articles

Exploratory biomarker analysis from a phase II clinical trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine for HER2-negative metastatic breast cancer patients (KCSG BR13-11).

We conducted an exploratory biomarker study from a phase II clinical trial of eribulin plus gemcitabine (EG) versus paclitaxel plus gemcitabine (PG) in HER2-negative metastatic breast cancer (BC) patients. We performed targeted deep sequencing with a customized cancer gene panel and RNA expression assay. Tumor mutation burden (TMB) and mutation signatures were determined based on genetic alteration in targeted regions. Gene set variation analysis was performed with PanCancer Immune Profiling and PanCancer Pathway Panels. Statistical analyses were conducted to identify the associations between genetic alterations and clinical outcomes. Of 119 patients, 40 had available biomarker data. Among the 40 patients, 4 supported their post-treatment tissues. In targeted deep sequencing, FAT3 (48%) was the most frequently mutated gene, followed by PKHD1, TP53, GATA3, PARP4, and PIK3CA. In terms of gene expression, low expression of epithelial-mesenchymal transition (EMT) pathway genes was associated with prolonged progression-free survival (PFS) in the EG group, while high expression of the EMT pathway was associated with good prognosis in the PG group. Median TMB was 6.5 (range 2.44-46.34) and there was no relationship between TMB and patient prognosis. Analysis of mutation signatures showed that signatures 3, 20, and 26 were frequently observed in our cohort. Further survival analysis according to mutation signature showed that mutation signature 3, as a homologous recombinant deficiency-related signature, was highly associated with disease progression (hazard ratio (log2 scale) 8.21, 95% confidence interval 2.93-13.48, p = 0.002). Kaplan-Meier plot also showed that BCs with signature 3 had short PFS compared to those without these signatures (median PFS (months) for signature 3 (low vs. high): 17.2 vs. 8.1, p = 0.0026). Mutation signature 3, found in about 30% of MBCs regardless of hormone receptor status, was associated with short PFS for patients with cytotoxic chemotherapy. ClinicalTrials.gov number: NCT02263495.

Quality of life outcomes including neuropathy-associated scale from a phase II, multicenter, randomized trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first-line chemotherapy for HER2-negative metastatic breast cancer: Korean Cancer Study Group Trial (KCSG BR13-11)

BackgroundA phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy-taxane (FACT-Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL).MethodsQoL was assessed using the Korean version of the FACT-Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms.ResultsOf the 118 enrolled patients, 117 responded to the FACT-Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2–13 cycles of chemotherapy (all P < 0.05), except for the 11th cycle. Neuropathy-specific analysis showed that patients in the PG arm had earlier and more severe neuropathic symptoms than those in the EG arm (P < 0.001).ConclusionsIn our QoL analysis, the EG regimen delayed and decreased neuropathy as compared with the PG regimen. Therefore, eribulin would be a reasonable substitute for paclitaxel as first-line chemotherapy for MBC.

Abstract P3-11-07: Exploratory biomarker analysis from a phase II, multicenter, randomized trial of eribulin plus gemcitabine(EG) versus paclitaxel plus gemcitabine(PG) as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer(MBC): Korean cancer study group trial (KCSG BR13-11)

Abstract Introduction : A phase II, multicenter, randomized clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first-line chemotherapy for patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) found EG was less neurotoxic, but had similar efficacy of PG. In this study, we performed exploratory biomarker analysis of the impact of genetic alterations on the efficacy according to EG and PG chemotherapy. Methods : This biomarker study was conducted using tumor samples from 40patients. When tissue collection was possible after disease progression, we performed paired sample analysis. Tumor DNA and RNA were extracted from formalin-fixed, paraffin-embedded tissues. To perform targeted deep sequencing, we used CancerScanTM, a 375 cancer gene panel. And we performed an nCounter expression assay for gene expression analysis using 730 PanCancer panel and 730 Immune panel. Results: In total, we obtained 44 tissue samples from 40 patients. Twenty two patients were assigned in EG arm and 18 patients were in PG arm. Thirty-eight were at baseline and six after disease progression. Gene expression assay were performed in 44 tissue samples but only 31 samples were possible to be targeted deep sequencing. We performed differently expressed gene(DEG) analysis for detecting the association between level of gene expression and disease progression. In this analysis, high expression of CCNE1, TGFB4 and BAMBI and low expression of DDB2, CD14 and SHC3 were associated with disease progression among 730 PanCancer panel genes (p&amp;lt;0.05, respectively). In terms of immune panel genes, most of immune related genes were highly expressed in a group without disease progression compared with that with disease progression. Only 2 genes, C8G and CD24 were highly expressed in a group with disease progression. Paired sample analysis showed that expression levels of THBS4 and CD27 decreased after disease progression while those of CCNE2 and FGFR4 increased. In targeted deep sequencing, FAT3 (42.3%) was most frequently mutated gene followed by PKHD1, PIK3CA and TP53. Among mutated genes, EWSR1 mutation and upstream mutation of ETV1 were associated with disease progression, respectively (p&amp;lt;0.05, respectively). In mutation signature analysis, signature 1 (S, age related), S3(homologous recombination deficiency, HRD), S6 (mismatch repair, MMR), S20(MMR) and S21(microsatellite instability, MSI) were enriched in this population. Mutation signature 3 related to short disease free survival (p=0.0026). Conclusion: In gene expression analysis, high expression of TGF-B signaling pathway related genes was associated with disease progression while high expression of immune related genes were related to prolonged disease free survival. In mutation analysis, EWSR1 and ETV1 mutations indicated short disease free interval and HRD mutation signature was also related to poor prognosis. Citation Format: Kim J-Y, Lee EJ, Park KH, Im S-A, Kim S-B, Sohn SH, Lee KS, Chae YS, Lee KH, Kim JH, Im Y-H, Kim T-Y, Lee K-H, Ahn J-H, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH, Park YH. Exploratory biomarker analysis from a phase II, multicenter, randomized trial of eribulin plus gemcitabine(EG) versus paclitaxel plus gemcitabine(PG) as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer(MBC): Korean cancer study group trial (KCSG BR13-11) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-07.

Quality of life(QoL) outcomes including neuropathy associated scale (FACT-T) from a phase II, multicenter, randomized trial of eribulin plus gemcitabine(EG) versus paclitaxel plus gemcitabine(PG) as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer(MBC): Korean Cancer Study Group trial (KCSG BR13-11).

10117Background: A phase II, multicenter, randomized clinical trial of EG and PG as first-line chemotherapy for patients with HER2-negative MBC showed that EG was less neurotoxic, but conferred a s...

Abstract OT1-01-12: A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer as first-line chemotherapy

Abstract Background: Metastatic breast cancer (MBC) is an incurable disease and is needed to improve effective chemotherapy. Paclitaxel plus Gemcitabine (PG) combination chemotherapy is one of the preferred chemotherapeutic regimens for patients with MBC, and was found to be proper as a maintenance chemotherapy regimen with survival benefit and feasible toxicity profile. Eribulin mesylate is a non-taxane inhibitor of microtubule dynamics of the halichondrin class of antineoplastic drugs. A recent pooled analysis of two phase II studies with eribulin showed improved overall survival in in various patient subgroups with advanced/metastatic breast cancer who had previously received an anthracycline and a taxane. Furthermore, eribulin may have rational benefit compared with paclitaxel in terms of neurotoxicity. Therefore, Eribulin plus Gemcitabine (EG) combination chemotherapy may have less neurotoxocity comparing to PG. Trial Design: Prospective randomized phase 2, open-label, two-arm, multi-center study comparing EG chemotherapy with PG chemotherapy for patients with HER-2 negative MBC as first-line chemotherapy. Eligibility Criteria: Histologically confirmed breast cancer patients, at least 19 years of age, with no prior history of chemotherapy for metastatic, recurrent breast cancer with evaluable lesions (as per RECIST, 1.1) who have adequate hematologic, renal, and hepatic function. Patients either may or may not have a prior anthracycline containing regimen. Prior hormonal therapy as a treatment of metastatic disease is allowed. Specific Aims: The primary efficacy endpoint of the trial is Progression-Free Survival (PFS). The secondary efficacy endpoints are: Time to Treatment Failure (TTF); Overall Survival (OS); neuropathic scale (FACT for Taxane QOL assessment); toxicity; duration of response; Objective Response Rate (ORR); Clinical Benefit Rate. The exploratory endpoint of the study includes pharmacogenetic profile. Statistical Methods: The initial sample size of the present study was determined based on the data derived from a previous trial on PG maintenance chemotherapy design; 6-month PFS is 70% for PG chemotherapy. This design was hypothesized that EG chemotherapy would not be inferior to PG chemotherapy. Thus, estimated PFS for each arm is 70%. Based on this estimate, we would plan to recruit a total of 100 patients (50 per arm). Considering drop-out rate of 10%, total 112 MBC patients planned to be enrolled. Present Accrual and Target Accrual:Enrollment has been completed as of March, 2016 with a target enrollment of 112 patients. Contact information:Kyung Hae Jung MD, Ph.D. khjung@amc.seoul.kr ClinicalTrials.gov Identifier: NCT02263495. Citation Format: Park YH, Im S-A, Sohn JH, Lee KS, Chae YS, Lee KH, Kim J-H, Im Y-H, Ahn JS, Kim T-Y, Lee K-H, Kim S-B, Ahn J-H, Kim GM, Park IH, Lee SJ, Han HS, Kim SH, Jung KH. A phase II, multicenter, randomized trial of eribulin plus gemcitabine (EG) vs. paclitaxel plus gemcitabine (PG) in patients with HER2-negative metastatic breast cancer as first-line chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-12.

P1.07-009 Outcomes of Patients with Relapsed Small-Cell Lung Cancer Treated with Paclitaxel plus Gemcitabine. 10 Year-Analysis

We conducted a retrospective study to investigate the outcome and prognostic factors of patients with relapsed SCLC who receive second or third line chemotherapy with paclitaxel plus gemcitabine, a regimen that is used in our institution since a phase II trial in 2001. We reviewed the medical records of patients with SCLC who received paclitaxel plus gemcitabine in a ten-year period, since 2005 from 2015. Overall survival (OS) from the initiation of this regimen was evaluated, plus characteristics of these patients. Patients diagnosed of SCLC were selected from our lung cancer database, and compared with our Pharmacy Department database. We selected all patients with relapsed SCLC that received therapy with paclitaxel plus gemcitabine (PG) at any moment of the disease. The median age of the cohort was 58 years (43–81 years). There were 69 males (83.2%) and 14 females (16.8%). 72 patients (86.7%) had a previous history of smoking. ECOG PS at relapse was 0 in 3 (3.6%), 1 in 70 (84.3%), and 2 in 10 (12.1%) patients. Fifty patients (60.2%) had extensive disease at baseline diagnosis, and the remaining 33 (38.8%) had limited disease. All patients were exposed previously to etoposide and platinum. The platinum used was cisplatin in 52 patients (60.3%) and carboplatin in 30 patients (38.7%). Previous radiation at local tumor site was received by 38 patients (45.8%). The response was evaluated in 78 patients. The response post-2 months of PG was complete response in 2 patients (2.5%), partial response in 29 (37.1%), stable disease in 24 (30.7%), and progressive disease in 23 patients (30.6%). The median number of cycles of PG received was 8 (2-28) cycles. Toxicity related cessation of treatment was required in 12 patients (14.4%). The reason for stoppage was Grade 3–4 toxicities in 8 patients (9.6%) and deterioration in PS in 4 patients (4.8%) The median PFS was 148 days (95% CI: 30–173.5 days) while the median OS was 172 days (95% CI: 60–485 days). Paclitaxel plus gemcitabine it is a well-tolerated regimen in relapsed SCLC in the schedule we usually use (every 2 weeks). Unless this study is retrospective, we believe that this combination can be used nowadays in these patients, if there is no clinical trial available.

PR99 QUALITY OF LIFE (QOL) IN METASTATIC BREAST CANCER PATIENTS WITH MAINTENANCE PACLITAXEL PLUS GEMCITABINE (PG) CHEMOTHERAPY: RESULTS FROM PHASE III, MULTICENTER, RANDOMIZED TRIAL OF MAINTENANCE CHEMOTHERAPY VERSUS OBSERVATION (KCSG-BR07-02)

The therapeutic goals are palliative for metastatic breast cancer (MBC) and include prolongation of survival with good quality of life (QoL) and symptom control. The purpose of this study was to examine QoL among women with MBC treated on KCSG-BR07-02 with maintenance of paclitaxel plus gemcitabine (PG) chemotherapy after achieving disease control to initial six cycles of PG chemotherapy or observation. Patients were randomized to either maintenance chemotherapy or observation until progression. QoL was assessed using EORTC QLQ-C30 and BR-23. QoL at each cycle was compared between the two treatment arms using the 2-sample t test. Generalized estimating equation method was used to examine the overall difference between the two treatments in QoL. All reported p-values are 2 sided. There were no statistically significant differences between two arms in most of the component of the EORTC QLQ-C30 and BR-23 (p > 0.05). There was no significant difference between two treatments (p = 0.6094 for QLQ-C30, p = 0.5516 for BR23) at baseline, and there did not exist significant change over the cycle (p = 0.0914 for QLQ-C30, p = 0.7981 for BR23). There was no significant interaction effect between treatment and cycle (p = 0.5543 for QLQ-C30. p = 0.5817 for BR23). Maintenance PG chemotherapy in patients with MBC achieving disease control with an initial six cycles of PG chemotherapy resulted in better PFS and OS compared to observation without impeding QoL.

Association between single nucleotide polymorphism (SNPs) of CYP3A4 and SLC28A3 and clinical outcome in metastatic breast cancer (MBC) patients receiving paclitaxel plus gemcitabine (PG) chemotherapy as first-line treatment.

1088 Background: Paclitaxel and gemcitabine (PG) combination chemotherapy is an effective regimen in metastatic breast cancer (MBC) patients as first-line chemotherapy. The primary purpose of our study was to investigate the association of the single nucleotide polymorphisms (SNPs) and clinical outcome in MBC patients treated with PG chemotherapy. Methods: A total of 324 MBC patients were enrolled in this prospective multicenter trial as the first-line chemotherapy. Eighty five of 324 patients were available for SNP analysis. Germline DNA from peripheral blood (PB) mononuclear cells was extracted. SNPs in 15 genes (27 SNPs) from pathways that may influence cellular sensitivity to paclitaxel and gemcitabine were genotyped from PB sample. Results: Median progression free survival (PFS) and overall survival (OS) of all 324 patients was 8.7 months (95% CI: 7.5-9.6 mo.) and 26.9 months (95% CI: 23.6-30.1 mo.), respectively. Among clinical parameters, young age (p = 0.047, HR 1.03 [95% CI, 1-1.07]), positive hormonal receptor status (p = 0.0004, HR 0.26 [95% CI, 0.12-0.54]), and hepatic metastasis (p = 0.046, HR 2.30 [95% CI, 1.02-5.18]) were identified predictive factors for OS in Cox-regression analysis. SLC28A3 SNP which participates in transcription showed correlation with OS. OS of the patients with CC and CT genotypes in SLC28A3 was significantly longer than the OS of the patients with TT genotype (median OS: 31 vs. 37 vs. 21 months, p = 0.027, HR 2.6 [95% CI, 1.1-6.3]). OS of the patients with TT genotype in CYP3A4 was significantly longer than the OS of the patients with TC genotype (median OS: 37 vs. 19 months, p = 0.021, HR 5.8 [95% CI, 1.3-25.7]). After adjusting hormonal receptor status, age, and hepatic metastasis, prognostic value of SLC28A3 remained significant (HR 2.9, p = 0.047). Other SNPs were not significantly associated with PFS, OS, or toxicities. Conclusions: SLC28A3 SNP can predict with the clinical outcome of MBC patients treated with PG chemotherapy. Further studies for functional mechanism of germline polymorphisms in SLC28A are warranted.

Efficacy and tolerability of biweekly gemcitabine plus cisplatin (GEMCIS) or gemcitabine plus paclitaxel (GEMPAC) as neoadjuvant chemotherapy in patients with muscle invasive urothelial carcinoma of the bladder.

e15006 Background: Cisplatin, gemcitabine and paclitaxel are active chemotherapeutic agents for invasive urothelial carcinoma of the bladder (UCB). Biweekly administration of gemcitabine in combination with cisplatin (GEMCIS) or paclitaxel (GEMPAC) has been reported to have better tolerability than other schedules. Methods: Between 2009- 2011, we have treated 34 patients (median age 69 years, range 56-85) with muscle invasive UCB using gemcitabine (1500 mg/m2) in combination with cisplatin (50 mg/m2) or paclitaxel (150 mg/m2) given on days 1 and 15, every 4 weeks, for 3 cycles prior to radical cystectomy (RC) with bilateral pelvic lymph node dissection and urinary diversion. Patients deemed unsuitable for GEMCIS due to old age, frailty, multiple comorbidities or poor renal function received GEMPAC (n=9); all others received GEMCIS (n=25). Results: Clinical staging revealed T2, T3 and T4 disease in 20 (58.8 %), 8 (23.5 %) and 6 (17.6 %) patients, respectively. Patients were re-evaluated after 2 cycles with MRI or CT scans, which showed improvement in 21 (61.8 %) patients, no change in 12 (35.3 %) and progression in 1 patient (2.9%). Pathologic examination of the surgical specimens revealed T0, Tis, T2, T3 and T4 disease in 8 (23.5 %), 6 (17.6 %), 10 (29.4 %), 6 (17.6 %) and 4 (11.8 %) patients, respectively. Overall, pathologic downstaging was observed in 41.1% of patients. In the GEMCIS group, 12 patients (48%) had pT0 or pTis; in the GEMPAC group, 2 pts (22.2%) had pT0 disease. The most commonly observed toxicities are tabulated below. Conclusions: Biweekly GEMCIS or GEMPAC regimens were active and exceptionally well tolerated in the neoadjuvant setting in patients with muscle invasive UCB, producing favorable pathologic outcomes in an initial cohort of patients. To our knowledge, these data represent the first report detailing clinical results with these regimens in this setting. [Table: see text]

Gemcitabine Plus Paclitaxel Versus Paclitaxel Monotherapy in Patients With Metastatic Breast Cancer and Prior Anthracycline Treatment

The objective of this phase III global study was to compare the efficacy of gemcitabine plus paclitaxel (GT) versus paclitaxel in patients with advanced breast cancer. It was designed as a pivotal study for the approval of G for a breast cancer treatment indication. Patients who relapsed after adjuvant anthracyclines were randomly assigned to gemcitabine,1,250 mg/m(2) days 1 and 8 plus paclitaxel, 175 mg/m(2) on day 1; or, to paclitaxel at same dose on day 1 (both arms administered every 21 days, unblinded). The primary end point was overall survival (OS) and secondary end points were time to progression (TTP), response rate (RR), progression-free survival, response duration, and toxicity. This final OS analysis was planned at 380 deaths. A total of 266 patients were randomly assigned to GT and 263 to paclitaxel. Median survival on GT was 18.6 months versus 15.8 months on paclitaxel (log-rank P = . 0489), with an adjusted Cox hazard ratio of 0.78 (95% CI, 0.64 to 0.96; P = .0187). The TTP was longer (6.14 v 3.98 months; log-rank P = .0002) and the RR was better (41.4% v 26.2%; P = .0002) on GT. There was more grade 3 to 4 neutropenia on GT and grade 2 to 4 fatigue and neuropathy were slightly more prevalent on GT. This phase III study documents a role for gemcitabine in advanced breast cancer after anthracycline-based adjuvant therapy. The results establish GT as a reasonable choice for women who require cytoreduction with manageable toxicities and validate ongoing testing of GT in the adjuvant setting.

Clinical Interpretation of Quality-of-Life Outcomes: An Investigation of Data from the Randomized Trial of Gemcitabine Plus Paclitaxel Compared with Paclitaxel Alone for Advanced Breast Cancer

Quality-of-Life (QL) data are increasingly relevant to trial results, but are often difficult to interpret and apply clinically; methods to address this problem are needed. Exploratory analyses were conducted using QL data from a recent phase III trial comparing front line gemcitabine plus paclitaxel (GT) versus paclitaxel (T) alone in patients with advanced breast cancer. The most troublesome symptom and toxicity items were identified. For each QL domain, associations and change over time were analyzed using clinically relevant data. The impact of tumor response and duration of therapy on QL outcomes was assessed using pooled data from both treatment arms. Baseline QL data were available from 336 patients, out of 266 patients enrolled on the GT arm and 263 patients enrolled on the T arm. The prevalence of disease-related symptoms was low; 7 of the 10 most troublesome items were psychological. Clinical levels of psychological distress were significantly associated with global QL and reduced significantly over time in both arms. Improved QL was significantly associated with reduced functional impairment, tumor response and completing more cycles of therapy. In this patient population, QL may be closely associated with the clinical efficacy of chemotherapy, functional status and psychological well-being, rather than outcomes such as symptom palliation and toxicity.

Phase II Study of Gemcitabine Plus Paclitaxel in Metastatic Breast Cancer Patients with Prior Anthracycline Exposure

Chemotherapy provides palliation and modest prolongation of symptom-free survival in metastatic breast cancer. Taxane containing regimens are commonly considered to be among the initials in metastatic setting due to earlier use of anthracyclines in the course of breast cancer. Therefore, we conducted this Phase II study to assess efficacy and safety of gemcitabine plus paclitaxel (GT) combination therapy in anthracycline pretreated metastatic first-line setting. Patients and Methods: The study enrolled 26 women with pathologically confirmed and measurable metastatic breast cancer who were previously treated with anthracycline but no prior chemotherapy for metastatic disease. Twenty six and twenty four patients were eligible for toxicity and efficacy evaluations respectively. Mean age was 47.3 years and median ECOG performance status was 0. Twenty patients (76.9 percent) had visceral metastases, most commonly located in liver and lung. Treatment schedule was as follows: paclitaxel 175 mg/m2 was administered intravenously in 3 hours on Day 1 and gemcitabine 1000 mg/m2 was administered intravenously in 30 minutes on Day 1 after paclitaxel application, and on Day 8 every 21 days. Results: Objective response rate was 41.7 percent (95 percent CI: 21.9–61.4) with 16.7 percent (95 percent CI: 1.7–31.6 percent) CR, and 25.0 percent (95 percent CI: 7.6–42.3 percent) PR. Median time to progression and overall survival were 9.6 and 14.5 months, respectively. Grade 3–4 toxicity was observed in 34.6 percent (9) patients. Treatment of two patients was discontinued due to toxicity, consisting of Grade 3 hypersensitivity reactions and Grade 4 infections in one patient each. Dose reductions due to myelotoxicity were performed in 4 (15.3 percent) patients. Hematologic toxicities were generally manageable with appropriate dose modifications and supportive care. Conclusion: Gemcitabine and paclitaxel combination regimen is effective and has manageable toxicity profile as first line metastatic setting.

Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall surviva

510 Background: GT had phase II safety and efficacy in MBC after anthracyclines, so it was compared to T in a phase III study of frontline therapy. Accrual goals were met in 4/02 and at initial planned interim analysis, GT significantly improved time to progression (TTP), progression-free survival (PFS), objective response rates (ORR) and quality of life, with an acceptable toxicity profile (PASCO 22:161, 2003). It was uncertain if this would translate into overall survival (OS) benefit, the primary endpoint of the trial. This report presents the first OS analysis. Methods: Patients (pts) with measurable MBC, prior (neo)adjuvant anthracyclines and KPS ≥70 were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21 days to progression. With median follow-up of 15.6 mos (all but 1 pt off study), the first OS analyses by Kaplan-Meier and Cox regression were conducted at approximately 75% (343) of the deaths needed (440) for the planned final OS report. (All p-values are 2-sided; confidence intervals, 95%.) Results: Characteristics of the 529 eligible pts (267 GT, 262 T) with visceral-dominant disease; toxicity; and the significant benefit from GT in ORR, TTP and PFS were previously reported (ref. above). 38% on GT stopped therapy due to progression vs 55% on T; therapy ended due to adverse events in 6.7%, GT vs 5.0%, T. The OS hazard ratio (HR) was 0.775 (.627, .959) in favor of GT, p=.018. Median OS for GT was 18.5 mos (16.5–21.2) vs T, 15.8 mos (14.4–17.4). One-year survival was 70.7% (65.1–76.3%) for GT and 60.9% (54.8–66.9%) for T (p=.019). The HR in favor of GT persisted in Cox regression after adjusting for baseline covariates: 0.740 (.598, .915), p=.006. Second-line therapy was nearly identical between arms, except for a 4-fold greater use of gemcitabine in the T arm. Conclusions: GT provides significant OS advantage over T when both are given on a q3 week cycle, a result to be confirmed in the final planned analysis in late 2004. The TTP benefit predicted OS improvement with longer follow-up. GT should be considered a frontline regimen in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly

Global phase III study of gemcitabine plus paclitaxel (GT) vs. paclitaxel (T) as frontline therapy for metastatic breast cancer (MBC): First report of overall surviva

510 Background: GT had phase II safety and efficacy in MBC after anthracyclines, so it was compared to T in a phase III study of frontline therapy. Accrual goals were met in 4/02 and at initial planned interim analysis, GT significantly improved time to progression (TTP), progression-free survival (PFS), objective response rates (ORR) and quality of life, with an acceptable toxicity profile (PASCO 22:161, 2003). It was uncertain if this would translate into overall survival (OS) benefit, the primary endpoint of the trial. This report presents the first OS analysis. Methods: Patients (pts) with measurable MBC, prior (neo)adjuvant anthracyclines and KPS ≥70 were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21 days to progression. With median follow-up of 15.6 mos (all but 1 pt off study), the first OS analyses by Kaplan-Meier and Cox regression were conducted at approximately 75% (343) of the deaths needed (440) for the planned final OS report. (All p-values are 2-sided; confidence intervals, 95%.) Results: Characteristics of the 529 eligible pts (267 GT, 262 T) with visceral-dominant disease; toxicity; and the significant benefit from GT in ORR, TTP and PFS were previously reported (ref. above). 38% on GT stopped therapy due to progression vs 55% on T; therapy ended due to adverse events in 6.7%, GT vs 5.0%, T. The OS hazard ratio (HR) was 0.775 (.627, .959) in favor of GT, p=.018. Median OS for GT was 18.5 mos (16.5–21.2) vs T, 15.8 mos (14.4–17.4). One-year survival was 70.7% (65.1–76.3%) for GT and 60.9% (54.8–66.9%) for T (p=.019). The HR in favor of GT persisted in Cox regression after adjusting for baseline covariates: 0.740 (.598, .915), p=.006. Second-line therapy was nearly identical between arms, except for a 4-fold greater use of gemcitabine in the T arm. Conclusions: GT provides significant OS advantage over T when both are given on a q3 week cycle, a result to be confirmed in the final planned analysis in late 2004. The TTP benefit predicted OS improvement with longer follow-up. GT should be considered a frontline regimen in MBC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Eli Lilly Eli Lilly

Gemcitabine plus paclitaxel (GT) versus paclitaxel (T) as first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Quality of life (QoL) and pain palliation results from the global phase III study

621 Background: At ASCO 2003, interim results of GT vs T in MBC patients (pts) were presented (#25), demonstrating significantly longer time to disease progression for GT with manageable toxicity. Here we present the results of the pain and QoL assessments. Methods: Pts with MBC with prior (neo)adjuvant anthracyclines were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21d. Pts completed the Brief Pain Inventory (BPI) and Rotterdam Symptom Checklist (RSCL) prior to each cycle; only data from validated translations were included. Analgesic level was assessed prior to each cycle. Mixed effect repeated-measure analysis was used to study overall and cycle-specific differences. This abstract presents the results of sensitivity analyses with five longitudinal models (e.g., pattern mixture models) that were performed to study potential bias due to informative dropout. Results: 529 pts were randomized (267 GT and 262 T). Arms were balanced; 70% had visceral metastases and 72% had KPS 90. Median cycles were 6 for GT (range, 0–20) and 5 for T (range, 0–16). 291 pts completed BPI and 350 completed RSCL. 85% of expected questionnaires were completed. The mean RSCL global QoL score for patients receiving GT was significantly and consistently better than that reported by T arm patients; this difference was also clinically significant. No consistent differences were seen in the other RSCL scales. Mean changes and trends in pain intensity and interference were similar across treatment arms. Data from the sensitivity analyses consistently supported these findings. Of pts requiring analgesics at baseline (n=216), more GT pts were able to decrease analgesic level for >1 cycle (25 vs 15%). Conclusions: For pts with MBC, the addition of gemcitabine to paclitaxel extended time to progression and resulted in a better global rating of QoL. The combination palliated pain as well as monotherapy in the predominantly asymptomatic population. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co.

Gemcitabine plus paclitaxel (GT) versus paclitaxel (T) as first-line treatment for anthracycline pre-treated metastatic breast cancer (MBC): Quality of life (QoL) and pain palliation results from the global phase III study

621 Background: At ASCO 2003, interim results of GT vs T in MBC patients (pts) were presented (#25), demonstrating significantly longer time to disease progression for GT with manageable toxicity. Here we present the results of the pain and QoL assessments. Methods: Pts with MBC with prior (neo)adjuvant anthracyclines were randomized to GT (G 1250 mg/m2 d1,8; T 175 mg/m2 d1) or T (175 mg/m2 d1) q21d. Pts completed the Brief Pain Inventory (BPI) and Rotterdam Symptom Checklist (RSCL) prior to each cycle; only data from validated translations were included. Analgesic level was assessed prior to each cycle. Mixed effect repeated-measure analysis was used to study overall and cycle-specific differences. This abstract presents the results of sensitivity analyses with five longitudinal models (e.g., pattern mixture models) that were performed to study potential bias due to informative dropout. Results: 529 pts were randomized (267 GT and 262 T). Arms were balanced; 70% had visceral metastases and 72% had KPS 90...

Paclitaxel plus carboplatin, compared with paclitaxel plus gemcitabine, shows similar efficacy while more cost-effective: a randomized phase II study of combination chemotherapy against inoperable non-small-cell lung cancer previously untreated

BackgroundPaclitaxel (Taxol) plus carboplatin (PC) has shown activity in the treatment of advanced non-small-cell lung cancer (NSCLC). Non-platinum-containing combination chemotherapy, such as paclitaxel plus gemcitabine (PG), has also demonstrated reasonable efficacy. Our aim here was to evaluate the clinical efficacy and cost-effectiveness of PC versus PG in chemo-naive, advanced NSCLC patients. Patients and methodsNinety (68 male, 22 female) patients were enrolled from August 1999 to August 2000. The performance status was one in 29 patients and two in 16 patients of the PC group, and one in 24 patients and two in 21 patients of the PG group. Seventeen patients had stage IIIb disease and 28 patients stage IV disease in the PC group; 18 patients had stage IIIb disease and 27 patients stage IV disease in the PG group (New International Staging System). Treatment consisted of P 175 mg/m2 and C at AUC = 7 (predicted using measured clearances and the Calvert formula) intravenous infusion (i.v.) on day 1, or P 175 mg/m2 i.v. on day 1 and G 1000 mg/m2 i.v. on days 1 and 8, every 3 weeks. ResultsIn all, 175 cycles of PC and 184 cycles of PG were given in the PC and PG groups, respectively. The median treatment cycle was four cycles in both groups. All the patients were assessable for toxicity and response measurement. There were three complete responses and 15 partial responses (overall 40%) in the PC group, and no complete response, but 18 partial responses (overall 40%) in the PG group. WHO grades 3/4 leukopenia, anemia and thrombocytopenia occurred in six (13.3%), seven (15.5%) and five patients (11.1%) in the PC group; and in four (8.9%), six (13.3%) and 0 patients in the PG group, respectively. Two patients in each group suffered from grade 3 peripheral neuropathy. Other non-hematological toxicities were mild and few. Median survival time was 14.1 months in the PC group and 12.6 months in the PG group. One-year survival was 50.7% in the PC group and 53.3% in the PG group. The PG group had a higher total expense and expended more days undergoing treatment than the PC group (P = 0.034 and 0.069, respectively). ConclusionsBoth PC and PG combination chemotherapy produce a similar efficacy in the treatment of NSCLC. However, PC is more cost-effective than PG.