An interim evaluation of efficacy and safety of the combination of panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 328-328
Author(s):  
Weijing Sun ◽  
Davendra Sohal ◽  
Kristine Mykulowycz ◽  
Ursina R. Teitelbaum ◽  
Nevena Damjanov ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Infusion Reaction ◽  
Primary Objective ◽  
Over Expression ◽  
Epidermal Growth ◽  
Efficacy Criteria ◽  
Tissue Specimens ◽  
Ecog Ps

328 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches suggest that combinations may be superior to single agents in this disease. Over-expression of epidermal growth factor receptor (EGFR) is associated with tumor stage and prognosis. This study was designed to evaluate the efficacy and tolerability of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan in patients with advanced and metastatic cholangiocarcinoma. Methods: Pts with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective was to evaluate the 5-month progression-free survival (PFS) rate. The secondary objectives include overall response rate (ORR), overall survival rate (OS) and toxicity of the combination. Results: There have been 24 (of planned 42) pts recruited to the study. Toxicity of the combination was assessed in all enrolled pts. There were no treatment related deaths. The most common gr 3 or higher toxicity was were neutropenia (10 pts [40%]), thrombocytopenia (6 pts, [25%]), skin rash (4 pts [17%]) and diarrhea (3 pts, [12%]). One pt developed a gr 2 infusion reaction, which was considered related to panitumumab. Efficacy was evaluated in 20 pts. Among them, there were 2 CR, 6 PR, and 10 SD (with disease control rate of 90%), and 2 PD (assessed by RECIST criteria). Two pts went on to have surgical resection. Eight pts had ≥ 10 cycles of the therapy, and dose modification/interruption were needed for some of these pts. Conclusions: The data of this on-going study showed encouraging results of the combination of panitumumab with gemcitabine and irinotecan in both tolerability and efficacy. The pre-specified efficacy criteria to continue enrollment were met. Further analysis by biomarker status (KRAS/BRAF/EGFR) is forthcoming.

A phase II trial of gemcitabine, irinotecan, and panitumumab in advanced cholangiocarcinoma, with correlative analysis of EGFR, KRAS, and BRAF: An interim report.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4111-4111
Author(s):  
Davendra Sohal ◽  
Ursina R. Teitelbaum ◽  
Takeshi Uehara ◽  
Kristine Mykulowycz ◽  
Christopher D. Watt ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Tumor Stage ◽  
Primary Objective ◽  
Response To Therapy ◽  
Braf V600e ◽  
Braf Mutations ◽  
Kras Mutations ◽  
Tissue Specimens

4111 Background: Cholangiocarcinoma is an aggressive neoplasm. Current chemotherapy approaches achieve modest results. The epidermal growth factor receptor (EGFR) pathway appears to be associated with tumor stage, prognosis and response to therapy. This trial was designed to evaluate the tolerability and efficacy of the combination of panitumumab, a monoclonal anti-EGFR antibody, with gemcitabine and irinotecan, in patients with advanced cholangiocarcinoma. Molecular analysis of EGFR pathway genes was planned as well. Methods: Patients with advanced (unresectable or metastatic) cholangiocarcinoma, ECOG PS 0-2, and adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, and gemcitabine (1000 mg/m2) and irinotecan (100 mg/m2) on days 1 and 8 of a 21-day cycle. Tissue specimens were collected at diagnosis for correlative molecular analyses. Primary objective is to evaluate the 5-month progression-free survival (PFS) rate. Secondary objectives include overall response rate (ORR), overall survival (OS) and toxicity of the combination. Mutational analysis of EGFR (del 19; 858), KRAS (codons 12, 13) and BRAF (V600E) was done on samples with adequate material for testing. Results: There have been 26 (of planned 42) patients recruited to the study. A median of 6 (0-30) cycles were administered. There were no treatment related deaths. The most common gr 3 or higher toxicities were neutropenia (10 pts, 38%), thrombocytopenia (10 pts, 38%), skin rash (10 pts, 38%) and diarrhea (3 pts, 12%). During the study, there were 3 CR, 6 PR, 10 SD (disease control rate of 90%), and 2 PD (by RECIST) in 21 evaluable pts. Two pts went on to have surgical resection. Median OS is 12.7 months. Of 13 testable samples, no EGFR or BRAF mutations were identified; however, there were 7 KRAS mutations. Retrospective analysis showed no difference in OS by KRAS mutation status. Conclusions: Interim evaluation of this ongoing study showed encouraging tolerability and efficacy of this regimen. Several patients have KRAS mutations; there appears to be no association with response, however. The pre-specified efficacy criteria to continue enrollment were met.

Panitumumab antitumor activity in patients (pts) with metastatic colorectal cancer (mCRC) expressing low (1–9%) or negative (<1%) levels of epidermal growth factor receptor (EGFr)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3547-3547 ◽  
Author(s):  
J. Hecht ◽  
E. Mitchell ◽  
J. Baranda ◽  
I. Malik ◽  
D. Richards ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Human Monoclonal Antibody ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Response Duration ◽  
Infusion Reaction ◽  
Prior Therapy ◽  
Epidermal Growth ◽  
Tumor Expression

3547 Background: Panitumumab is a fully human monoclonal antibody directed against EGFr. We investigated the antitumor activity of panitumumab in pts with mCRC who failed prior therapy and had low or negative EGFr tumor expression. Methods: In this multicenter, phase 2 study of 150 planned pts, pts had documentation of disease progression (PD) during or after adequate doses of fluoropyrimidine, irinotecan, and oxaliplatin (centrally confirmed refractory disease [CCRD]), 2–3 prior regimens, ECOG score 0–2, and low or negative EGFr staining (by IHC) in evaluable tumor cells. Pts received panitumumab at 6 mg/kg Q2W until PD or drug intolerability. Tumor assessments (modified WHO, blinded central review) were taken periodically from wk 8 until PD. Endpoints were objective response (OR) through wk 16 (+ ≥ 4 wk confirmation; primary) and OR throughout study, response duration, progression-free survival (PFS) time, survival time, and safety (secondary). Results: In this interim analysis (6/05), 88 pts were enrolled and had ≥ 1 dose of panitumumab (safety set); 23 pts had ≥ 20 wks before the cutoff and CCRD (efficacy set). The efficacy set consisted of 16M/7W, median age of 65 (range: 46, 85) yrs, 83% white, 100% with ECOG ≤ 1, 74% colon cancer and 26% rectal cancer; all received ≥ 2 prior regimens (equivalent characteristics for safety set). 2/11 (18%) pts with EGFr-negative tumors and 1/12 (8%) with low EGFr staining had a partial response. Duration was up to 16 wks. 7/23 (30%) of all pts had SD. Median (95% CI) PFS was 7.9 (7.0, 23.0) wks. In the safety set, all pts had a treatment-related adverse event; 19% grade (gr) 3; 2% gr 4. Integument and eye toxicities were: 92% skin, 17% eye, 28% nail, 8% hair, and 2% chelitis. 20 (23%) had diarrhea (1 gr 3); 7 (8%) had hypomagnesemia (2 gr 3/4). Three pts had an infusion reaction-1 gr 3 (led to panitumumab discontinuation) and 2 gr 1/2. In 65 pts with both a baseline and post-baseline sample, no human anti-human antibodies to panitumumab were detected. Updated data will be presented. Conclusions: Responses to panitumumab were seen in pts with mCRC with both low and negative EGFr levels. Efficacy appears similar to that in other studies with panitumumab in pts with higher EGFr tumor levels. [Table: see text]

Erlotinibversuscarboplatin and paclitaxel in advanced lepidic adenocarcinoma: IFCT-0504

2015 ◽  
Vol 46 (5) ◽  
pp. 1440-1450 ◽  
Author(s):  
Jacques Cadranel ◽  
Radj Gervais ◽  
Patrick Merle ◽  
Denis Moro-Sibilot ◽  
Virginie Westeel ◽  
...  
Keyword(s):  
Disease Control ◽  
Dominant Role ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
First Line ◽  
First Line Therapy ◽  
Epidermal Growth ◽  
Progression Risk ◽  
Pathological Subtypes

The IFCT-0504 phase II trial evaluated the efficacy of erlotinibversuscarboplatin–paclitaxel (CP) as first-line treatment in 130 cases of advanced lepidic-predominant adenocarcinoma (ADC).The primary objective of the study was treatment efficacy, evaluated based on an end-point of disease control at 16 weeks.The primary objective was met, with a disease control in 35 (53%) out of 66 patients treated with CP and in 25 (39.1%) out of 64 patients treated with erlotinib. Median progression-free survival (PFS) for the total population was 3.6 months. The disease control rate did not differ between either the therapeutic arms or pathological subtypes, whereas there was a strong interaction between treatment arms and tumour pathological subtypes for PFS (p=0.009). Mucinous tumour patients treated with erlotinib exhibited an increased progression risk (hazard ratio 3.4, 95% CI 1.7–6.5; p≤0.001). The PFS for nonmucinous tumour patients was similar in both arms. Median overall survival was 20.1 months and did not differ between therapeutic arms. These findings were not further elucidated by molecular analyses and the toxicity profiles were as expected.Our study demonstrated the dominant role of CP alongside erlotinib in the management of advanced lepidic ADC. Based on these findings, erlotinib should not be administered in first-line therapy to patients with lepidic ADC in the absence of an epidermal growth factor receptor mutation.

Safety and antitumor activity of ramucirumab plus pembrolizumab in treatment naïve advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma: Preliminary results from a multi-disease phase I study (JVDF).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 101-101 ◽  
Author(s):  
Ian Chau ◽  
Nicolas Penel ◽  
Hendrik-Tobias Arkenau ◽  
Rafael Santana-Davila ◽  
Emiliano Calvo ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Median Duration ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Antitumor Effects ◽  
Treatment Naïve ◽  
Ecog Ps

101 Background: Preclinical evidence suggests simultaneous blockade of vascular endothelial growth factor receptor 2 (VEGFR-2) and programed cell death 1 protein (PD-1) induces synergistic antitumor effects. We assessed safety and preliminary efficacy of ramucirumab (anti-VEGFR-2) plus pembrolizumab (anti-PD-1) in patients (pts) with treatment naïve advanced G/GEJ adenocarcinoma. Methods: This ongoing, multi-cohort, phase 1a/b trial enrolled ECOG PS 0-1 pts with treatment naïve advanced G/GEJ adenocarcinoma with measurable disease and baseline tumor tissue. PD-L1 status was assessed by DAKO PD-L1 22C3 IHC pharmDx assay using the combined positive score with ≥1% being positive. Ramucirumab was administered at 8 mg/kg on Days 1 & 8 with pembrolizumab 200 mg on Day 1 q3W. Primary objective was safety and tolerability of study treatment; preliminary efficacy was examined. Results: As of 31-July-2017, 28 treatment naïve G/GEJ adenocarcinoma pts were treated. Median age was 63 y, 75% male, 57% had ECOG PS of 0, and 68% were PD-L1 positive. At data cutoff, 8 (28%) pts continued to receive study treatment. Median duration of follow-up was 8.1 mo (IQR 6-10). Median treatment duration was 4.3 mo (IQR 2-7). All grades treatment-related adverse events (TRAEs) occurred in 27 (96%) of patients; TRAEs in ≥15% of pts were fatigue (36%), hypertension (25%) and headache (18%). Seventeen (61%) pts experience grade 3 TRAEs, most commonly hypertension (14%), diarrhea (11%), and elevated alanine (7%) or aspartate (7%) aminotransferase. No grade 4-5 TRAEs occurred. An objective response was achieved by 7 (25%) pts, 6 positive and 1 negative for PD-L1. Disease control rate was 68%. Median time to response was 2.7 mo (95% CI 1.3-2.8) and median duration of response was 10 mo (95% CI 9.7-10.3). Median progression-free survival was 5.3 mo (95% CI 3.2-11). Median overall survival has not been reached. Conclusions: Ramucirumab plus pembrolizumab demonstrated encouraging antitumor activity in treatment naïve advanced G/GEJ adenocarcinoma with no grade 4 TRAE observed. Clinical trial information: NCT02443324.

A phase II study of capecitabine-oxaliplatin and cetuximab in patients (pts) with advanced/metastatic gastric cancer (G) or gastroesophageal junction (GEJ) adenocarcinoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Syma Iqbal ◽  
Anthony B. El-Khoueiry ◽  
Dongyun Yang ◽  
David Páez ◽  
Vinay Duddalwar ◽  
...  
Keyword(s):  
Phase Ii ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Metastatic Gastric Cancer ◽  
Primary Objective ◽  
Kras Mutations ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Egf Signaling

4096 Background: There have been limited advances in the treatment (tx) of pts with metastatic G or GEJ adenocarcinoma. The combination of fluroropyrimidines and platinums are standard regimens for this disease. The epidermal growth factor receptor pathway has been identified as a target and KRAS mutations are rare. Methods: The primary objective was to assess the proportion of pts with progression within 4 months. Secondary objectives include response (RR), progression free survival (PFS) overall survival (OS), toxicity and molecular correlates. A two-stage Simon phase II design was used to distinguish between a 30% vs. 50% 4 month PFS; with analysis planned at 27 and 53 pts. Eligible pts were chemonaive, metastatic/unresectable with measurable disease. Pts received capecitabine 850 mg/m2 BID D1-14, oxaliplatin 130 mg/m2 IV D1, cetuximab 400 mg/m2 (load) then 250 mg/m2 IV D1, 8, 15, q21 days. Blood and tissue were analyzed for genes in the DNA repair and EGFR pathways. Results: 61 pts were accrued, 2 GEJ and 59 G; 42 male, 19 female; median age 56 years (28-86); 54 pts were evaluable. The 4 month PFS rate 61% (95%CI 47-73%), PFS 5.4 months (95% CI 3.5-6.7); RR 50% (95%CI: 36-64%), 1 (1.9%) complete, 26 (48.1%) partial, 22 (40.7%) stable disease; 2 (3.7%) pts became resectable; median OS 14.9 months (95% CI 8.8-22.2) with median follow-up of 21.8 months. 65% (39/60) of pts had grade 3 (36 pts) or 4 (3 pts) toxicity; most common, anorexia (13.3%), diarrhea (13.3%), fatigue (13.3%), nausea (15%), vomiting (15%); grade 3 hand/foot (5.3%), acneiform rash (3.3%). SNP’s in LRIG4, (regulator of EGF signaling) and PAI1 (tumor angiogenesis, cell proliferation, migration and adhesion) were significantly associated with RR (67% G/G vs 17% A/A ,p=0.044) and PFS (5.8 months 5G/4G vs 3.4 months 5G/5G, p=0.017) respectively. Conclusions: XELOX and cetuximab has promising activity, comparable to existing regimens. Novel SNP’s were identified correlating with RR and PFS which may allow for optimization of pt selection.

scholarly journals Frequency and Prognosis of Epidermal Growth Factor Receptor Variant III Mutations in Glioblastoma Multiforme among Indian Patients: A Single-Institution Study

2020 ◽  
Vol 09 (03) ◽  
pp. 126-129
Author(s):  
Wesley Mannirathil Jose ◽  
Vinayak Munirathnam ◽  
V. Narendranath ◽  
Arun Philip ◽  
Pavithran Keechilat
Keyword(s):  
Growth Factor ◽  
Glioblastoma Multiforme ◽  
Epidermal Growth Factor ◽  
World Literature ◽  
Mutational Analysis ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Rank Test ◽  
Cancer Center ◽  
Epidermal Growth

Abstract Background Glioblastoma multiforme (GBM) is a disease with poor outcome. Alterations or mutations in epidermal growth factor receptors (EGFRs) are found in GBM and may be targeted to improve outcomes. Aims We analyzed the frequency of EGFR variant III (vIII) mutations in patients with GBM and their outcomes after standard treatment. Materials and Methods This is a retrospective study conducted in a single tertiary cancer center in south India. Forty patients with GBM who had their entire treatment done at this center were identified, and their primary tumor tissue blocks were retrieved. Genomic DNA was extracted, and molecular analysis was performed and analyzed. The results of mutational analysis were correlated with treatment outcome of the patients. Statistical Analysis Survival outcome was analyzed using the Kaplan–Meier method. The log-rank test was used to assess the association between the groups and various parameters. Results Our study showed a similar incidence of EGFR vIII alterations as published in world literature, but we did not find any difference in overall survival (OS) and progression-free survival (PFS) in patients with EGFR vIII mutation compared with nonmutant cohort. Conclusions Contrary to the existing literature which indicated EGFR vIII alterations to be a negative prognostic indicator, our study did not find it to be an independent predictor of prognosis among Indian GBM patients treated with present standard of care.

scholarly journals Better Progression-Free Survival in Elderly Patients with Stage IV Lung Adenocarcinoma Harboring Uncommon Epidermal Growth Factor Receptor Mutations Treated with the First-line Tyrosine Kinase Inhibitors

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 434 ◽  
Author(s):  
Ming-Ju Tsai ◽  
Jen-Yu Hung ◽  
Mei-Hsuan Lee ◽  
Chia-Yu Kuo ◽  
Yu-Chen Tsai ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Kinase Inhibitors ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Egfr Mutations ◽  
First Line ◽  
Free Survival ◽  
Younger Patients ◽  
Epidermal Growth

Patients with lung adenocarcinoma harboring common epidermal growth factor receptor (EGFR) mutations usually have a good response rate (RR) and longer progression-free survival (PFS) to EGFR tyrosine kinase inhibitors (TKIs). However, the treatment efficacy to uncommon EGFR mutations remains controversial. We, therefore, performed a retrospective study, screening 2958 patients. A total of 67 patients with lung adenocarcinoma harboring uncommon EGFR mutations were enrolled and 57 patients with stage IV diseases receiving a first-line EGFR TKI were included for further analyses. The patients were classified into 27 (47%) “a single sensitizing uncommon mutation”, 7 (12%) “multiple sensitizing mutations”, 5 (9%) “a sensitizing mutation and a resistant uncommon mutation”, and 18 (32%) “other resistant uncommon mutations”. No significant difference was noted in PFS or overall survival (OS) between groups. Patients receiving different first-line EGFR TKIs had similar PFS and OS. The elder patients had a significantly poorer performance status than the younger patients but a significantly longer PFS than the younger patients (median PFS: 10.5 vs. 5.5 months, p = 0.0320). In conclusion, this is the first study to identify that elderly patients with stage IV lung adenocarcinoma harboring uncommon EGFR mutation might have a longer PFS. Large-scale prospective studies are mandatory to prove our findings.

scholarly journals CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease

2018 ◽  
Vol 10 ◽  
pp. 175883591881834 ◽  
Author(s):  
Adriana Matutino ◽  
Carla Amaro ◽  
Sunil Verma
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Growth Factor Receptor ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Breast Cancers ◽  
Cyclin Dependent Kinase ◽  
Her2 Positive ◽  
Hormone Receptor Positive ◽  
Epidermal Growth

The development of cyclin-dependent kinase (CDK) 4/6 inhibitors has been more prominent in hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancers, with a significant improvement in progression-free survival (PFS) in first and later lines of metastatic breast cancer (MBC) therapy. Preclinical evidence suggests that there is activity of CDK4/6 inhibitors in nonluminal cell lines. Here, we present a review of the current preclinical and clinical data on the use of CDK inhibitors in HER2-positive and triple-negative breast cancer (TNBC).

scholarly journals Long-term remission of a Her2/neu positive primary breast cancer under double monoclonal antibody therapy with trastuzumab and bevacizumab

2014 ◽  
Vol 48 (2) ◽  
pp. 184-188 ◽  
Author(s):  
Robert Königsberg ◽  
Julia Maierhofer ◽  
Tanja Steininger ◽  
Gabriele Kienzer ◽  
Christian Dittrich
Keyword(s):  
Breast Cancer ◽  
Case Report ◽  
Growth Factor ◽  
Antibody Therapy ◽  
Growth Factor Receptor ◽  
Over Expression ◽  
Single Target ◽  
Epidermal Growth ◽  
Endothelial Growth Factor

AbstractBackground. The attempt to act on several signalling pathways involved in tumour development simultaneously appears to be more attractive than attacking a single target structure alone. Vascular endothelial growth factor (VEGF) over-expression is frequently observed in human epidermal growth factor receptor 2 (Her2/neu) positive patients with breast cancer and over-expression of the proto-oncogene Her2/neu is associated with an up-regulation of VEGF.Case report. The case of a Her2/neu positive patient with breast cancer who refused cytotoxic chemotherapy with its potential side effects as well as mastectomy is presented. Our patient has been receiving the combined double administration of bevacizumab and trastuzumab for more than 4 years.Conclusions. This case report shows that (a) the combined double administration of bevacizumab and trastuzumab was be clinically effective. (b) The combination of bevacizumab and trastuzumab is safe and non-toxic. (c) Bevacizumab and trastuzumab can be used as a long-term application

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