FOLFIRI in advanced biliary tract cancers.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 451-451 ◽  
Author(s):  
Jonathan Mizrahi ◽  
Valerie Gunchick ◽  
Kabir Mody ◽  
Lianchun Xiao ◽  
Phani Keerthi Surapaneni ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Group Performance ◽  
Performance Status ◽  
Treatment Options ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Extrahepatic Cholangiocarcinoma ◽  
Biliary Tract Cancers

451 Background: Gemcitabine plus platinum (GP) is the standard of care first-line treatment for advanced biliary tract cancers (BTC). There is no established second-line therapy, and retrospective reviews report progression-free survival (PFS) for second-line treatment to be < 3 months. 5-Fluorouracil plus irinotecan (FOLFIRI) is a commonly used regimen in patients (pts) with BTC who have progressed on GP, though there is a paucity of data regarding its efficacy in this population. Methods: We retrospectively evaluated pts with advanced BTC who were treated with FOLFIRI at MD Anderson, University of Michigan and Mayo Clinic in Jacksonville. Data were obtained on pt demographics, type of BTC, PFS, and overall survival (OS). Results: Ninety-eight pts were included of which 74 (76%) had metastatic disease at the time of treatment with FOLFIRI. The median age was 59 (range, 22 to 86) years. The number of pts with extrahepatic cholangiocarcinoma (CCA)/gall bladder (GB)/intrahepatic CCA were 10, 17, and 71. FOLFIRI was used as 1st, 2nd, 3rd or 4th – Nth lines in 8, 50, 36, and 4 pts, respectively. Of the 65 pts whose best responses were documented, 23 (35%) had stable disease and 7 (11%) had a partial response per RECIST v1.1. Median duration on FOLFIRI was 2.2 months. The median PFS and OS were 2.4 (95% CI 1.7 to 3.1) and 6.6 (95% CI 4.7 to 8.4) months, respectively. Median PFS for pts treated with FOLFIRI in 1st, 2nd, 3rd or 4th – Nth lines were 3.1, 2.5, 2.3 and 1.5 months, respectively. Eighteen pts received concurrent bevacizumab (13) or EGFR-targeted therapy (5) with FOLFIRI, and both of groups exhibited a median PFS of 2.7 months. Eastern Cooperative Oncology Group performance status (PS) of 0-1 was associated with improved OS (P = 0.006) compared to PS of 2-3. Conclusions: In this multi-institution retrospective review of 98 pts with BTC treated with FOLFIRI, efficacy of this regimen appears to be modest. While PFS and OS outcomes were similar to what has been previously reported, the 46% disease control rate in this group of predominantly pretreated pts is encouraging. Given the lack of other standard therapies, FOLFIRI may still have a role in this pt population, but these results emphasize the need for more effective treatment options for pts with advanced, pretreated BTC.

Randomized Phase III Study of Panitumumab With Fluorouracil, Leucovorin, and Irinotecan (FOLFIRI) Compared With FOLFIRI Alone As Second-Line Treatment in Patients With Metastatic Colorectal Cancer

2010 ◽  
Vol 28 (31) ◽  
pp. 4706-4713 ◽  
Author(s):  
Marc Peeters ◽  
Timothy Jay Price ◽  
Andrés Cervantes ◽  
Alberto F. Sobrero ◽  
Michel Ducreux ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
Second Line ◽  
Kras Status

PurposePanitumumab is a fully human anti–epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone after failure of initial treatment for mCRC by tumor KRAS status.Patients and MethodsPatients with mCRC, one prior chemotherapy regimen for mCRC, Eastern Cooperative Oncology Group performance status 0 to 2, and available tumor tissue for biomarker testing were randomly assigned 1:1 to panitumumab 6.0 mg/kg plus FOLFIRI versus FOLFIRI every 2 weeks. The coprimary end points of PFS and overall survival (OS) were independently tested and prospectively analyzed by KRAS status.ResultsFrom June 2006 to March 2008, 1,186 patients were randomly assigned 1:1 and received treatment. KRAS status was available for 91% of patients: 597 (55%) with wild-type (WT) KRAS tumors, and 486 (45%) with mutant (MT) KRAS tumors. In the WT KRAS subpopulation, when panitumumab was added to chemotherapy, a significant improvement in PFS was observed (hazard ratio [HR] = 0.73; 95% CI, 0.59 to 0.90; P = .004); median PFS was 5.9 months for panitumumab-FOLFIRI versus 3.9 months for FOLFIRI. A nonsignificant trend toward increased OS was observed; median OS was 14.5 months versus 12.5 months, respectively (HR = 0.85, 95% CI, 0.70 to 1.04; P = .12); response rate was improved to 35% versus 10% with the addition of panitumumab. In patients with MT KRAS, there was no difference in efficacy. Adverse event rates were generally comparable across arms with the exception of known toxicities associated with anti-EGFR therapy.ConclusionPanitumumab plus FOLFIRI significantly improved PFS and is well-tolerated as second-line treatment in patients with WT KRAS mCRC.

Long-term benefit (LTB) of sunitinib (SU) treatment for metastatic renal cell carcinoma (mRCC): Retrospective analysis for clinical biomarkers identification.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 465-465
Author(s):  
Oren Smaletz ◽  
Matias Chacon ◽  
Ludmila de Oliveira Koch ◽  
Daniela Regina de Carvalho Rocha ◽  
Fernanda Camila Cardoso
Keyword(s):  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Predictive Marker ◽  
Common Finding ◽  
Second Line ◽  
Clinical Biomarkers ◽  
Metastatic Sites

465 Background: Prospective studies with sunitinib in mRCC have shown median progression-free survival (mPFS) of 11 months (first line) and 8.3 months (second line). In order to identify patients with LTB with SU, we describe the clinical characteristics of patients with mRCC treated with SU with an mPFS of 15 months or more. Methods: This is a retrospective chart review of patients with mRCC treated with SU in two hospitals, Alexander Fleming Institute Buenos Aires in Argentina and Hospital Israelita Albert Einstein in Sao Paulo, Brazil. Inclusion criteria included patients treated with SU who had a PFS of at least 15 months. Results: Between September 1995 and August 2009, 29 cases were identified. Patient demographics were: median age of 56 years, 65% male, 96% with previous nephrectomy, Eastern Cooperative Oncology Group performance status (PS) of either 0 (52%) or 1 (48%), 93% had clear cell histology, 69% received prior systemic therapy, and 78% had ≤ 2 metastatic sites (mostly in the lungs, liver and bone). Patients were started on SU 50 mg 4 weeks on treatment/2 weeks off treatment (4/2) (n=26) or 37.5 mg 6 weeks continuous dosing (n=3). For those patients starting on 4/2, dose reduction was necessary in 59% of the patients to maintain SU therapy. Median duration of therapy was 23.7 months. During treatment, 24 patients (83%) developed hypertension. Response rates were as follows: complete response 7% (n=2), partial response 38% (n=11), stable disease 52% (n=15); data missing for one patient. Conclusions: LTB is seen in patients who are young, have good performance status, and either 1 or 2 metastatic sites. Dose reductions are common in order to maintain treatment while benefiting from SU. Treatment with SU as either first- or second-line therapy did not appear to influence outcome. Hypertension is a common finding and serves as a predictive marker during treatment, but study limitations preclude the identification of pre-treatment predictive factors.

The landscape of MET mutations in Chinese biliary tract cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16652-e16652
Author(s):  
Shifeng Xu ◽  
Wei Rao ◽  
Yuanwen Zheng ◽  
Jianping Wang ◽  
Weiyu Hu ◽  
...  
Keyword(s):  
Gene Amplification ◽  
Biliary Tract ◽  
Clinical Laboratory ◽  
Performance Status ◽  
Treatment Options ◽  
Copy Number Variations ◽  
Chinese Patients ◽  
Gene Rearrangements ◽  
Extrahepatic Cholangiocarcinoma ◽  
Biliary Tract Cancers

e16652 Background: Biliary tract cancers (BTCs) are malignancies with poor prognosis and limited treatment options. MET is recurrently altered in various cancers that confer susceptibility to targeted MET inhibitors. It has been reported that the MET mutation frequency is 2-7% in intrahepatic cholangiocarcinoma (ICC) and 3.7% in extrahepatic cholangiocarcinoma (ECC) in Western countries. However, the characterization of MET in Chinese BTCs are not clear. Methods: Next-generation sequencing (NGS) targeting 450 cancer genes was performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matching blood samples that collected from a cohort of 926 Chinese BTC patients. Genomic alterations, including single nucleotide variations (SNV), short and long insertions/deletions (Indels), copy number variations, and gene rearrangements/fusions, were analyzed. The testing was carried out by a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Results: MET mutations were detected in 4.1% of patients with BTCs, including 5.3% in ICC, 3.4% in hilar cholangiocarcinoma (HCCA), 3.0% in ECC, and 2.6% in gallbladder cancer (GBCA). Gene amplification was the most common type of MET mutation in BTC (2.6%) compared with gene rearrangements/fusions (1.1%) and SNV (0.9%). Novel MET fusion partners, including TNS3 and TRIM4, and MET exon 14 skipping mutation, were also detected. There was no difference in tumor mutational burden (TMB) between patients with and without MET mutation (average TMB: 6.5 vs. 5.6 muts/Mb, P= 0.213). Among these BTC patients, an advanced ICC patient (performance status [PS] 3) who harbored MET gene amplification, received crizotinib as the first-line treatment. Four months later, the patient had a complete response without obvious side effects. Conclusions: To our knowledge, this is the largest BTCs cohort and the first report of MET mutation profiling in the Chinese patients. MET mutations were detected in 4.5% BTCs, and MET inhibitors may be potential treatment options for BTC patients. All types of MET mutations, including gene amplification, SNVs, and gene fusions, were detected in BTCs, which demonstrated that NGS might be a powerful tool to detect MET mutations. Altogether, MET is a promising target in BTCs, and detection of MET mutations is important and essential for predicting the sensitivity of targeted therapy. Clinical trial information: NCT03892577 .

185 Camrelizumab monotherapy or combination therapy in patients with recurrent or metastatic cervical and endometrial carcinoma:a retrospective study

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A199-A199
Author(s):  
Hong Liu ◽  
Shuhuai Niu ◽  
Zhaohui Fang ◽  
Xi Chen ◽  
Qianying Zhang
Keyword(s):  
Combination Therapy ◽  
Adverse Events ◽  
Endometrial Carcinoma ◽  
Group Performance ◽  
Antitumour Activity ◽  
Performance Status ◽  
Treatment Options ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival

BackgroundPatients with recurrent or metastatic cervical and endometrial carcinoma have poor prognosis and few treatment options. Blocking the interaction between PD-1 and its ligands is a promising treatment strategy. Camrelizumab is a humanised anti-programmed death-1 (anti PD-1) antibody. This study aimed to assess the anti-tumour activity and safety of camrelizumab in patients with recurrent or metastatic cervical and endometrial carcinoma.MethodsWe performed a retrospective analysis for recurrent or metastatic cervical and endometrial carcinoma patients. Eligible patients were aged 28–73 years with an Eastern Cooperative Oncology Group performance status of 0 or 2. Patients received camrelizumab alone(200 mg iv d1 q2w)or in combination with chemoradiotherapy/chemotherapy. The primary endpoint was objective response (ORR). The secondary endpoints included disease control rate (DCR), median progression-free survival (mPFS) and safety.ResultsA total of 21 patients were enrolled between September 20, 2019, and July 8, 2020. 18 patients were evaluated for efficacy and 21 patients were available for safety analysis. For 18 evaluated patients, the ORR and DCR was 50% (9/18) and 83.3% (15/18), respectively. In addition, 4 patients received camrelizumab monotherapy with the ORR of 0% (0/4) and DCR of 25% (1/4), and 14 patients received camrelizumab combination therapy with the ORR of 64.3% (9/14) and DCR of 100% (14/14). 16 of 21 patients were still receiving the treatment, the median PFS was not yet achieved. Exploratory analysis showed that patients with reactive cutaneous capillary endothelial proliferation (RCCEP) had the higher objective response rate than those without RCCEP (57.1% vs 45.5%). Treatment-related adverse events occurred in 47.6% (10/21) of patients, and the most common adverse events were RCCEP (33.3%), rash (14.3%), dry skin (9.5%). Treatment-related grade 3 adverse events occurred in 4.8% (1/21) of patients.ConclusionsCamrelizumab showed antitumour activity in recurrent or metastatic cervical and endometrial carcinoma with manageable toxicities. Camrelizumab combination therapy had better efficacy compared with monotherapy. RCCEP occurrence was positively associated with outcomes of camrelizumab. Further studies are needed to verify this data.

scholarly journals A Population-Based Retrospective Study of Biliary Tract Cancers in Alberta, Canada

2021 ◽  
Vol 28 (1) ◽  
pp. 417-427
Author(s):  
Carissa Beaulieu ◽  
Arthur Lui ◽  
Dimas Yusuf ◽  
Zainab Abdelaziz ◽  
Brock Randolph ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Demographic Data ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Intrahepatic Bile Duct ◽  
Population Based ◽  
Phase Iii ◽  
First Line ◽  
Biliary Tract Cancers

Background: Biliary tract cancers (BTC) are uncommon malignancies and are underrepresented in the literature. Methods: We performed a retrospective population-based review of adult patients with biopsy-confirmed BTC in Alberta from 2000 to 2015. Demographic data, risk factors, symptoms, treatment, and staging data were collected and analyzed. Survival analyses were completed. Results: A total of 1604 patients were included in our study, of which 766 (47.8%) were male. The median age at diagnosis was 68 (range 19–99). There were 374 (23.3%) patients with resectable tumors at diagnosis versus 597 (37.2%) with unresectable tumors. Of the patients, 380 (21.5%) received chemotherapy (CT) and 81 (5.0%) underwent radiation therapy. There was a clear trend with worsening stage and performance status associated with shorter median overall survival (OS). Ampulla of Vater tumors had the best median OS (25.69 months), while intrahepatic bile duct cancers had the worst (5.78 months). First-line palliative CT regimens included gemcitabine+cisplatin (OS 14.98 months (mo), n = 212), single agent gemcitabine (OS 12.42 mo, n = 22), capecitabine (OS 8.12 mo, n = 8), and capecitabine+gemcitabine (OS 6.93 mo, n = 13). Patients with advanced or metastatic disease who received first-line gemcitabine+cisplatin had a median OS of 11.8 months (n = 119). Conclusion: BTCs have poor survival. Worse outcomes occur in higher stage and poorer Eastern Cooperative Oncology Group (ECOG) performance status patients across all tumor subtypes. Tumor resectability at diagnosis was associated with better OS. Our study supports the use of gemcitabine+cisplatin as a combination first-line palliative CT, as patients treated in Alberta have a comparable OS to that reported in the ABC-02 phase III study.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Multicenter Phase 2 Study of Combined Gemcitabine and Epirubicin as Second-Line Treatment for Patients With Advanced Ovarian Cancer

2010 ◽  
Vol 20 (6) ◽  
pp. 953-957 ◽  
Author(s):  
Viviana Murgia ◽  
Roberto Sorio ◽  
Claudia Griso ◽  
Orazio Caffo ◽  
Carmela Arcuri ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Advanced Ovarian Cancer ◽  
Hematological Toxicity ◽  
Line Treatment ◽  
Second Line ◽  
Phase 2 ◽  
Platinum Resistant ◽  
Gynecology And Obstetrics

Objective:The aim of this phase 2 trial was to evaluate the tolerability and efficacy of combined gemcitabine (G) and epirubicin (E) as second-line treatment for patients with advanced ovarian cancer.Methods:Treatment with G 1000 mg/m2 (days 1 and 8) and E 60 mg/m2 (day 1) every 3 weeks for 3 or, in the absence of progression, 6 courses.Results:Fifty patients with advanced ovarian cancer (31 serous, 2 endometrioid, 10 unclassified adenocarcinoma, and 7 other) and a median age of 60 years (range, 38-74 years) were enrolled after giving their informed consent. Performance status according to the Eastern Cooperative Oncology Group was 0 in 29 patients (58%), 1 in 17 patients (34%), and 2 in 4 patients (8%), and the initial stages according to the International Federation of Gynecology and Obstetrics were I to II in 4 patients (8%), III in 31 patients (62%), and IV in 15 patients (30%). They had previously received a median of 1.5 lines of treatment (range, 1-4). The median platinum-free interval was 5 months (range, 0-12 months): 32 patients had relapse within 6 months and 18 patients had relapse after 6 months.The response rate was 42% (2% complete response and 40% partial response), with a median duration of 7.2 months: the corresponding figures were 37.5% and 5.2 months in the platinum-resistant patients and 50% and 8.8 months in the platinum-sensitive patients. The main grade 3 to 4 hematological toxicity was neutropenia (56% of cases). After a median follow-up of 13.5 months, median progression-free survival was 5 months, and median overall survival was 23.5 months.Conclusions:This E + G combination seems to be active and safe in platinum-resistant/refractory patients.

Efficacy of weekly paclitaxel-bevacizumab combination in advanced nonsquamous non-small cell lung cancer (NSCLC): AVATAX, a retrospective multicentric study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21086-e21086
Author(s):  
Geoffroy Bilger ◽  
Anne-Claire Toffart ◽  
Marie Darasson ◽  
Michaël Duruisseaux ◽  
Lucie Ulmer ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Second Line ◽  
Multicentric Study ◽  
Significant Difference ◽  
Third Line ◽  
And Performance ◽  
Line Setting

e21086 Background: With the growing role of immunotherapy (ICI) as first-line setting for advanced NSCLC, strategies must be redefined after failure. The combination paclitaxel-bevacizumab showed in the ULTIMATE trial a significant superiority versus docetaxel as second or third-line treatment. Limited restropective studies has demonstrated unexpected efficacy of chemotherapy after prior progression on ICI. This combination could be use as salvage treatment following ICI. Methods: This multi-centric retrospective study identifies patients treated with the combination paclitaxel-bevacizumab in metastatic non-squamous NSCLC as second-line therapy or beyond. Main objectives were to describe safety and efficacy of this combination, with a special attention to the sub-group treated just after ICI. Results: From January 2010 to February 2020, 314 patients started the paclitaxel-bevacizumab combination : 55% male, with a median age of 60 years, 27% with a performance status ≥2, 45% with brain metastases. A majority of patients were treated in second (20%) and third-line (39%), and 28% were treated just after ICI failure (88/314). Objective response rate (ORR) was 40% and disease control rate was 77 %. Median progression-free survival (PFS) and overall survival (OS) were 5,7 months [IQ,3,2–9,6] and 10,8 months [IQ,5,3–19,6] respectively. All grades adverse events concerned 82% of patients, including 53% asthenia and 39% neurotoxicity, and 25% of patients continued a monotherapy alone due to toxicity. Median PFS for patients treated after ICI failure (ICI+) was significantly superior compare to those not previously treated with ICI (ICI-) : 7,0 months [IQ,4,2–11,0] vs 5,2 months [IQ,2,9–8,8] p (log-rank) = 0,01. There was not statistically significant difference in term of OS between this two groups. In multivariate analysis, factors associated with superior PFS were previous ICI treatment (ICI+) and performance status. Conclusions: This study confirms an acceptable toxicity profile associated with interesting efficacy of the combination paclitaxel-bevacizumab as second-line treatment or beyond for non–squamous NSCLC patients, particularly after progression with ICI.

Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine

2017 ◽  
Vol 35 (30) ◽  
pp. 3433-3439 ◽  
Author(s):  
George D. Demetri ◽  
Patrick Schöffski ◽  
Giovanni Grignani ◽  
Jean-Yves Blay ◽  
Robert G. Maki ◽  
...  
Keyword(s):  
Subgroup Analysis ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Progression Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Eribulin Mesylate ◽  
Systemic Treatments ◽  
Phase Iii Study

Purpose A phase III study comparing eribulin with dacarbazine in patients with advanced liposarcoma (LPS) or leiomyosarcoma showed a significant improvement in overall survival (OS) for the eribulin arm, with a manageable toxicity profile. We now report the histology-specific subgroup analysis of the efficacy and safety of eribulin compared with dacarbazine in patients with LPS, an independently randomized stratified subgroup of this phase III trial. Methods Patients ≥ 18 years with advanced or metastatic dedifferentiated, myxoid/round cell, or pleomorphic LPS incurable by surgery or radiotherapy were included. Patients with Eastern Cooperative Oncology Group performance status ≤ 2 and two or more prior systemic treatment regimens, including one with anthracycline, were randomly assigned 1:1 to receive eribulin mesylate (1.4 mg/m2 intravenously on days 1 and 8) or dacarbazine (850, 1,000, or 1,200 mg/m2 intravenously on day 1) every 21 days. OS, progression-free survival (PFS), and safety were analyzed. Results In the LPS subgroup, OS was significantly improved: 15.6 versus 8.4 months (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P < .001) with eribulin versus dacarbazine, respectively. Longer OS with eribulin was observed in all LPS histologic subtypes and in all geographic regions evaluated. PFS was also improved with eribulin versus dacarbazine (2.9 v 1.7 months, respectively; hazard ratio, 0.52; 95% CI, 0.35 to 0.78; P = .0015). Adverse events were similar between arms. Conclusion In patients with previously treated LPS, eribulin was associated with significantly superior OS and PFS compared with dacarbazine. Eribulin represents an important treatment option for patients with LPS, a sarcoma subtype for which limited effective systemic treatments are available. Further studies are justified to explore the role of eribulin in earlier lines of therapy as well as in combination with other agents.

scholarly journals Efficacy and Safety of CAP7.1 as Second-Line Treatment for Advanced Biliary Tract Cancers: Data from a Randomised Phase II Study

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3149
Author(s):  
Ulrich-Frank Pape ◽  
Stefan Kasper ◽  
Johannes Meiler ◽  
Marianne Sinn ◽  
Arndt Vogel ◽  
...  
Keyword(s):  
Disease Progression ◽  
Biliary Tract ◽  
Phase Ii ◽  
Topoisomerase Ii ◽  
Clinical Investigation ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
Efficacy And Safety ◽  
Biliary Tract Cancers

CAP7.1 is a novel topoisomerase II inhibitor, converted to active etoposide via carboxylesterase 2 (CES2), with signals of efficacy in treatment-refractory solid tumours. In a Phase II trial, 27 patients with advanced biliary tract cancers (BTC) were randomised 1:1 to CAP7.1 plus best supportive care (BSC), or BSC alone, with crossover to CAP7.1 upon disease progression. The primary objective was disease control rate (DCR) following 28-day cycles of CAP7.1 (200/150 mg/m2; iv), or BSC until progression. Secondary objectives included progression-free survival (PFS), time-to-treatment failure (TTF), overall survival (OS) and safety. Fourteen patients received CAP7.1 and 13 BSC. DCR favoured CAP7.1 vs. BSC (50% vs. 20%; treatment difference: 30%, 95%CI −18.44, 69.22, full analysis set [FAS]), with disease progression in 40% vs. 70%, respectively. Significantly longer median PFS was achieved for CAP7.1 vs. BSC: 66 vs. 39 days, respectively (hazard ratio [HR] 0.31; 95%CI 0.11, 0.86; p = 0.009; FAS). Similar trends were observed for TTF and OS. CES2-positive patients had longer median PFS (158 vs. 56 days) and OS (228 vs. 82 days) vs. CES2-negative patients. Adverse events were predictable, dose-dependent and consistent with those previously observed with etoposide. These efficacy and safety findings in second-line BTC warrant further clinical investigation of CAP7.1.

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