Schwartzberg L.S.,West Clinic |
Arena F.P.,Arena Oncology Associates |
Mintzer D.M.,Pennsylvania Oncology Hematology Associates |
Epperson A.L.,Accelerated Community Oncology Research Network |
Walker M.S.,Accelerated Community Oncology Research Network
Clinical Breast Cancer | Year: 2012
Background: Capecitabine, a tumor-activated oral fluoropyrimidine, and albumin-bound paclitaxel (ab-paclitaxel) have substantial single-agent activity in patients with metastatic breast cancer (MBC). Taxane and antimetabolite doublets have improved efficacy compared with single agents. This phase II open-label trial was designed to test the safety and efficacy of capecitabine and ab-paclitaxel in previously untreated MBC. Patients and Methods: Patients received capecitabine (825 mg/m2 orally twice daily, approximately 12 hours apart, on days 1 to 15) and ab-paclitaxel (125 mg/m2 intravenously on days 1 and 8 of each cycle with no premedication) every 3 weeks. The primary endpoint was overall objective response rate (ORR), with evaluation performed after every 2 cycles. Entry criteria included measurable MBC, human epidermal growth factor receptor 2 (HER2) negativity, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, no previous chemotherapy for metastatic disease, and > 6 months since adjuvant fluoropyrimidine or paclitaxel treatment. Results: Fifty patients received at least 1 dose of study drug, with 46 patients evaluable for efficacy evaluation. Three hundred seventy-four cycles of therapy were delivered. Eighty percent of patients completed 8 cycles. The ORR was 61% (complete response [CR], 4%; partial response [PR], 57%), and 7 patients had sustained (≥ 24 weeks) stable disease for a clinical benefit rate of 76.1%. The median progression-free survival (PFS) was 10.6 months, and the median overall survival was 19.9 months. The most common adverse events (AEs) that were ≥ grade 3 were pain, hand-foot syndrome, and neutropenia. Conclusion: The combination of weekly ab-paclitaxel plus daily capecitabine orally at these doses and scheduling was well tolerated and showed substantial efficacy. © 2012 Elsevier Inc. All rights reserved.
Schwarzberg L.S.,West Clinic |
Franco S.X.,Memorial Cancer Institute |
Florance A.,Glaxosmithkline |
O'Rourke L.,Glaxosmithkline |
And 2 more authors.
Oncologist | Year: 2010
Objective. To evaluate the efficacy and tolerability of letrozole plus lapatinib versus letrozole plus placebo in women with hormone receptor (HR) + human epidermal growth factor receptor (HER)-2+ tumors receiving first-line therapy for metastatic breast cancer (MBC). Patients and Methods. Postmenopausal women (n = 1,286) with HR+ MBC were randomized to daily oral treatment with letrozole (2.5 mg) plus lapatinib (1,500 mg) versus letrozole (2.5 mg) plus placebo. Of the 1,286 patients enrolled in the phase III study, 219 had HER-2+ tumors. The primary endpoint was progression-free survival (PFS) in HER-2+ patients. Results. Results in the HR+ HER-2+ population (n = 219) are presented. The addition of lapatinib to letrozole resulted in a significantly lower risk for disease progression than with letrozole alone (hazard ratio, 0.71; 95% confidence interval, 0.53-0.96). The PFS time was 8.2 months, versus 3.0 months. The objective response rate (ORR) (28% versus 15%) and clinical benefit rate (CBR) (48% versus 29%) were also significantly greater in lapatinib-treated women. The most common adverse events in the lapatinib group were diarrhea (68%) and rash (46%), primarily grade 1 and 2. Conclusions. The addition of lapatinib to letrozole is well tolerated and leads to a significantly greater PFS time, ORR, and CBR than with letrozole alone in women with MBC who coexpress HR and HER-2. ©AlphaMed Press.
Wilks S.,Us Oncology Cancer Care Centers Of South Texas |
Puhalla S.,University of Pittsburgh |
O'Shaughnessy J.,Breast Cancer Research |
Schwartzberg L.,West Clinic |
And 4 more authors.
Clinical Breast Cancer | Year: 2014
Background The aim of this study was to assess efficacy and safety of eribulin with trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer. Patients and Methods In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2+ breast cancer received eribulin mesylate at 1.4 mg/m2 intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary end point was ORR, and secondary end points included PFS, TTR, DOR, and safety. Results Fifty-two patients were enrolled. Fifty-one patients (98.1%) had metastatic disease, 25 (48.1%) with liver metastases, 24 (46.2%) with lung metastases, and 19 (36.5%) with bone metastases. Patients received a median of 10.0 cycles of eribulin and 11.0 cycles of trastuzumab. The ORR was 71.2% (n = 37) with median TTR of 1.3 months, DOR of 11.1 months, and PFS of 11.6 months. The most common Grade 3/4 treatment-emergent adverse events were neutropenia in 20 (38.5%) patients, peripheral neuropathy in 14 (26.9%; all Grade 3) patients, fatigue in 4 (7.7%) patients, and febrile neutropenia in 4 (7.7%) patients. Conclusions Because of the high ORR, prolonged median PFS, and acceptable safety profile, combination eribulin/trastuzumab is an acceptable treatment option for locally recurrent or metastatic HER2+ breast cancer. © 2014 Elsevier Inc. All rights reserved.
McIntyre K.,Texas Oncology Dallas Presbyterian Hospital |
O'Shaughnessy J.,Texas Oncology Baylor Charles mmons Cancer Center |
Schwartzberg L.,West Clinic |
Gluck S.,University of Miami |
And 4 more authors.
Breast Cancer Research and Treatment | Year: 2014
Eribulin mesylate, a novel non-taxane microtubule dynamics inhibitor, is approved for treatment of metastatic breast cancer (MBC) in patients who have previously received at least 2 chemotherapeutic regimens for MBC that should have included an anthracycline and a taxane in the adjuvant or metastatic setting. This phase 2 study evaluated efficacy and safety of eribulin as first-line therapy for human epidermal growth factor receptor 2-negative (HER2-negative) MBC. Patients with measurable HER2-negative locally recurrent breast cancer or MBC with ≥12 months since prior neoadjuvant or adjuvant (neo/adjuvant) chemotherapy received eribulin mesylate 1.4 mg/m2 IV on days 1 and 8 of each 3-week cycle. Endpoints included objective response rate (ORR) per RECIST v1.1 (primary), safety, progression-free survival (PFS), clinical benefit rate (ORR + stable disease ≥6 months; CBR), and duration of response (DOR). Fifty-six patients were enrolled and received eribulin; 38 (68 %) had prior neo/adjuvant therapy, including 33 who had anthracycline and/or taxane-containing chemotherapy; 41 (73 %) had estrogen receptor-positive disease, and 12 (21 %) had estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) disease. Patients received a median of 7 cycles (range 1-43); 6 (11 %) received treatment for ≥12 months. ORR was 29 % (95 % CI 17.3-42.2), CBR was 52 %, and median DOR was 5.8 months. Median PFS was 6.8 months. Thirty-six patients (64 %) had grade 3/4 treatment-related adverse events; most common were neutropenia (50 %), leukopenia (21 %), and peripheral neuropathy (21 %). These results demonstrate that eribulin has substantial antitumor activity as first-line treatment for HER2-negative MBC with acceptable safety. © 2014 The Author(s).
Schwartzberg L.,West Clinic |
Barbour S.Y.,Duke University |
Morrow G.R.,University of Rochester |
Ballinari G.,Helsinn Healthcare SA |
And 2 more authors.
Supportive Care in Cancer | Year: 2014
Purpose: Preventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in preventing CINVassociated withmoderately or highly emetogenic chemotherapy. Methods: Patient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0-24 h), delayed (>24-120 h), and overall (0-120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity. Results: CR rates were significantly higher for palonosetron (n =1,787) versus older 5HT3 RAs (n =1,175) in the delayed (57 vs 45%, P <0.0001) and overall periods (51 vs 40%, P <0.0001); odds ratios (95% CI) in the acute, delayed, and overall periods were 1.15 (0.98-1.34), 1.62 (1.40-1.88), and 1.56 (1.34-1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0%; 0.75 mg, 26.5%) and older 5HT3 RAs (27.5%). Conclusions: Palonosetron is more effective than older 5HT3 RAs for controlling CINV in the delayed and overall post-chemotherapy periods. © The Author(s) 2013.
Chiappori A.A.,H. Lee Moffitt Cancer Center and Research Institute |
Schreeder M.T.,Clearview Cancer Institute |
Moezi M.M.,Integrated Community Oncology Network |
Stephenson J.J.,Institute for Translational Oncology Research |
And 7 more authors.
British Journal of Cancer | Year: 2012
Background: Bcl-2 family genes are frequently amplified in small cell lung cancer (SCLC). A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy. Methods: Eligible patients (3-6 per cohort) had extensive-stage SCLC, measurable disease, 1 before therapy, Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients were treated with escalating doses of obatoclax, either as a 3-or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m 2, days 1-3). The primary endpoint was to determine the maximum tolerated dose of obatoclax.Results:Twenty-five patients (56% male; median age 66 years) were enrolled in three dose cohorts for each schedule. Maximum tolerated dose was established with the 3-h infusion at 30 mg per day and was not reached with the 24-h infusion. Compared with the 24-h cohorts, the 3-h cohorts had higher incidence of central nervous system (CNS) adverse events (AEs); dose-limiting toxicities were somnolence, euphoria, and disorientation. These CNS AEs were transient, resolving shortly after the end of infusion, and without sequelae. The response rate was 81% in the 3-h and 44% in the 24-h infusion cohorts. Conclusion: Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day. Though patient numbers were small, there was a suggestion of improved efficacy in the 3-h infusion group. Obatoclax 30 mg infused intravenously over 3 h on 3 consecutive days will be utilised in future SCLC studies. © 2012 Cancer Research UK All rights reserved.
Klein R.,Medical Decision Modeling |
Wielage R.,Medical Decision Modeling |
Muehlenbein C.,Eli Lilly and Company |
Liepa A.M.,Eli Lilly and Company |
And 3 more authors.
Journal of Thoracic Oncology | Year: 2010
Introdution: The primary objective was to estimate the cost-effectiveness of maintenance therapy with pemetrexed (Pem) compared with observation, each with best supportive care, in patients with advanced non-small cell lung cancer (NSCLC) who have completed, without progression, at least four cycles of first-line platinum chemotherapy, particularly in those with nonsquamous cell histology. Secondary comparisons included Pem with erlotinib (Erl) or Pem with bevacizumab (Bev). Methods:A semi-Markov model was developed to compare the 3-year impact of Pem with three other alternatives for maintenance therapy from a United States payer perspective. Data from randomized controlled clinical trials provided clinical inputs. Medicare reimbursement rates were used to determine drug costs. A retrospective claims database analysis was used to obtain estimates of other direct NSCLC-related costs. Results: In the prespecified subset of patients with nonsquamous cell histology only, the incremental cost per life-year gained was $122,371 for Pem to observation and $150,260 for Pem to Erl, and Bev was dominated by Pem. In all patients with advanced NSCLC regardless of histologic subtype, using Pem as maintenance therapy led to an incremental cost per life-year gained of $205,597 compared with observation and $312,341 compared with Erl. Conclusions: Compared with observation and other agents used and/or reimbursed for maintenance therapy in advanced NSCLC, Pem may be considered cost-effective, particularly in patients with nonsquamous cell histology. This analysis is the first to evaluate the cost-effectiveness of maintenance therapy in advanced NSCLC and emphasizes the importance of histology in identifying the appropriate patient for Pem maintenance therapy. © 2010 by the International Association for the Study of Lung Cancer.
Tillmanns T.D.,West Clinic |
Lowe M.P.,Northwestern University |
Lowe M.P.,Advocate Christ Medical Center |
Walker M.S.,ACORN Research LLC |
And 2 more authors.
Gynecologic Oncology | Year: 2013
Objective: We examined the safety and efficacy of combining bevacizumab with albumin-bound (ab-) paclitaxel to treat patients with recurrent, platinum-resistant primary epithelial ovarian or peritoneal carcinoma. Methods: Patients had measurable disease per RECIST guidelines, progressing within 6 months after a prior course of platinum-based treatment. Patients received ab-paclitaxel 100 mg/m2 given by intravenous infusion over 30 min on days 1, 8, and 15 of a 28-day cycle with bevacizumab 10 mg/kg given on days 1 and 15. Results: Forty-eight patients with an average 1.8 prior lines of treatment participated. The overall response rate was 50% (24/48) (95% CI, 34.8% - 65.1%), with 4 complete and 20 partial responses. Fourteen patients (29%) had stable disease, whereas eight (17%) had progressive disease, and two (4%) were not evaluable. Patients received a median of 6 treatment cycles (range, 1 - 31 cycles). The median progression-free survival was 8.08 months (95% CI, 5.78 - 10.15 months); 6 month progression-free rate was 62.5% (95% CI, 47.8%-77.2%); median overall survival was 17.15 months (95% CI, 13.57 - 23.82 months). Grade 3-4 adverse events included gastrointestinal disorders (18.8%), neutropenia (8.3%), and hypertension (6.3%). Conclusions: Ab-paclitaxel with bevacizumab clearly demonstrates antitumor activity and manageable toxicity profile in patients with recurrent, platinum-resistant ovarian carcinoma. This regimen should be evaluated in a larger randomized trial. © 2012 Elsevier Inc. All rights reserved.
Schwartzberg L.,West Clinic
Expert Review of Pharmacoeconomics and Outcomes Research | Year: 2014
Chemotherapy-induced nausea and vomiting (CINV) is a troubling side effect of cancer treatment and is often poorly controlled. As a consequence, CINV is associated with substantially increased costs of care and significant interference with patients' lives. Inadequate control over CINV results from factors that include failure to provide guideline-adherent prophylactic medication and limitations in available therapies. Newer serotonin receptor antagonists, such as palonosetron, and addition of neurokinin-1 (NK-1) receptor antagonists to treatment have significantly decreased both acute and delayed CINV. A fixed-dose combination of palonosetron and a new NK-1 receptor, netupitant, is significantly superior to palonosetron alone and has small, but consistent, numerical advantages over aprepitant plus palonosetron for prevention of CINV. The combination of a serotonin receptor antagonist plus an NK-1 receptor antagonist has been shown to be cost-effective for prevention of CINV and the availability of a fixed-dose combination of netupitant and palonosetron may enhance this benefit. © 2014 Informa UK Ltd.
Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): A randomised, double-blind, multicentre, phase 3 study
Tabernero J.,Autonomous University of Barcelona |
Yoshino T.,National Cancer Center Hospital East |
Cohn A.L.,Rocky Mountain Cancer Center Us Oncology |
Obermannova R.,Comprehensive Care |
And 15 more authors.
The Lancet Oncology | Year: 2015
Background: Angiogenesis is an important therapeutic target in colorectal carcinoma. Ramucirumab is a human IgG-1 monoclonal antibody that targets the extracellular domain of VEGF receptor 2. We assessed the efficacy and safety of ramucirumab versus placebo in combination with second-line FOLFIRI (leucovorin, fluorouracil, and irinotecan) for metastatic colorectal cancer in patients with disease progression during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine. Methods: Between Dec 14, 2010, and Aug 23, 2013, we enrolled patients into the multicentre, randomised, double-blind, phase 3 RAISE trial. Eligible patients had disease progression during or within 6 months of the last dose of first-line therapy. Patients were randomised (1:1) via a centralised, interactive voice-response system to receive 8 mg/kg intravenous ramucirumab plus FOLFIRI or matching placebo plus FOLFIRI every 2 weeks until disease progression, unacceptable toxic effects, or death. Randomisation was stratified by region, KRAS mutation status, and time to disease progression after starting first-line treatment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01183780.ld. Findings: We enrolled 1072 patients (536 in each group). Median overall survival was 13·3 months (95% CI 12·4-14·5) for patients in the ramucirumab group versus 11·7 months (10·8-12·7) for the placebo group (hazard ratio 0·844 95% CI 0·730-0·976; log-rank p=0·0219). Survival benefit was consistent across subgroups of patients who received ramucirumab plus FOLFIRI. Grade 3 or worse adverse events seen in more than 5% of patients were neutropenia (203 [38%] of 529 patients in the ramucirumab group vs 123 [23%] of 528 in the placebo group, with febrile neutropenia incidence of 18 [3%] vs 13 [2%]), hypertension (59 [11%] vs 15 [3%]), diarrhoea (57 [11%] vs 51 [10%]), and fatigue (61 [12%] vs 41 [8%]). Interpretation: Ramucirumab plus FOLFIRI significantly improved overall survival compared with placebo plus FOLFIRI as second-line treatment for patients with metastatic colorectal carcinoma. No unexpected adverse events were identified and toxic effects were manageable. Funding: Eli Lilly. © 2015 Elsevier Ltd.