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.

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 Consensus on management of metastatic colorectal cancer in Central America and the Caribbean: San José, Costa Rica, August 2016

ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000315 ◽  
Author(s):  
Roberto Ivan López ◽  
Jenny Lissette Castro ◽  
Heidy Cedeño ◽  
Dagoberto Cisneros ◽  
Luis Corrales ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Growth Factor Receptor ◽  
Primary Objective ◽  
First Line ◽  
Epidermal Growth ◽  
The Caribbean

Colorectal cancer (CRC) is the third most common cancer in men and the second most common in women worldwide. In Latin America and the Caribbean, it has a mortality of 56%. The median overall survival for patients with metastatic colorectal cancer (mCRC) is currently estimated as ~30 months, which has substantially improved through strategic changes in treatment and in the management of patients. As opposed to other metastatic cancers where first-line regimens are often determined, mCRC requires special attention because there is controversy in the possible combinations of the available drugs and the different periods of duration for each patient. Each combination must seek to be effective and to generate the minimum adverse effects as possible. Instead of giving the first-line regimen until the tumour progresses, treatment is often individualised. Furthermore, up to 60% of colorectal tumours are considered non-mutated or wild-type CRC. Not harbouring mutations in the RAS family of genes or mutations in the signalling pathways of the epidermal growth factor receptor causes a null response to anti-epidermal growth factor receptor antibody therapy, which implies even more complex considerations regarding its management. The primary objective of this consensus is to address the main scenarios of mCRC in order to warrant the most appropriate therapeutic intervention for these patients in the Central American and the Caribbean (CAC) region. This can lead to better clinical outcomes as well as quality of life for palliative patients. This document includes the formal expert consensus recommendations for scenarios of mutated and non-mutated mCRC, including synchronous or metachronous disease, management of mCRC with liver and lung metastasis, resectable, potentially resectable or non-resectable tumours and local in the CAC context.

scholarly journals Phase II Randomized Trial Comparing Sequential First-Line Everolimus and Second-Line Sunitinib Versus First-Line Sunitinib and Second-Line Everolimus in Patients With Metastatic Renal Cell Carcinoma

2014 ◽  
Vol 32 (25) ◽  
pp. 2765-2772 ◽  
Author(s):  
Robert J. Motzer ◽  
Carlos H. Barrios ◽  
Tae Min Kim ◽  
Silvia Falcon ◽  
Thomas Cosgriff ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Second Line ◽  
First Line ◽  
First Line Therapy

Purpose A multicenter, randomized phase II trial, RECORD-3, was conducted to compare first-line everolimus followed by sunitinib at progression with the standard sequence of first-line sunitinib followed by everolimus in patients with metastatic renal cell carcinoma. Patients and Methods RECORD-3 used a crossover treatment design. The primary objective was to assess progression-free survival (PFS) noninferiority of first-line everolimus compared with first-line sunitinib. Secondary end points included combined PFS for each sequence, overall survival (OS), and safety. Results Of 471 enrolled patients, 238 were randomly assigned to first-line everolimus followed by sunitinib, and 233 were randomly assigned to first-line sunitinib followed by everolimus. The primary end point was not met; the median PFS was 7.9 months for first-line everolimus and 10.7 months for first-line sunitinib (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.8). Among patients who discontinued first-line, 108 (45%) crossed over from everolimus to second-line sunitinib, and 99 (43%) crossed over from sunitinib to second-line everolimus. The median combined PFS was 21.1 months for sequential everolimus then sunitinib and was 25.8 months for sequential sunitinib then everolimus (HR, 1.3; 95% CI, 0.9 to 1.7). The median OS was 22.4 months for sequential everolimus and then sunitinib and 32.0 months for sequential sunitinib and then everolimus (HR, 1.2; 95% CI, 0.9 to 1.6). Common treatment-emergent adverse events during first-line everolimus or sunitinib were stomatitis (53% and 57%, respectively), fatigue (45% and 51%, respectively), and diarrhea (38% and 57%, respectively). Conclusion Everolimus did not demonstrate noninferiority compared with sunitinib as a first-line therapy. The trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression.

A phase II study of gefitinib as a first-line therapy for advanced non-small cell lung cancers with epidermal growth factor receptor (EGFR) gene mutations

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13014-13014 ◽  
Author(s):  
H. Asahina ◽  
K. Yamazaki ◽  
I. Kinoshita ◽  
S. Ogura ◽  
T. Ishida ◽  
...  
Keyword(s):  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Small Cell Lung ◽  
First Line ◽  
Lung Cancers ◽  
Egfr Gene ◽  
First Line Therapy ◽  
Line Therapy ◽  
Epidermal Growth

13014 Background: Activating mutations in exon 18–21 of the epidermal growth factor receptor (EGFR) gene have been reported to be a predictor of response to gefitinib. We conducted a phase II study to evaluate the efficacy and safety of gefitinib as a first-line therapy for advanced non-small cell lung cancers (NSCLCs) with EGFR gene mutations. Methods: The primary endpoint was response rate (RR). Eligiblity criteria were stage IIIB or IV chemotherapy naive NSCLC, ECOG PS of 0–2, adequate organ functions, measurable lesions, and written informed consent. First, we examined EGFR gene mutations in exon 18–21 by direct sequencing of PCR products of DNA extracted from paraffin-embedded tissues. Those who had EGFR gene mutations received gefitinib 250 mg daily. This study, with a sample size of 14, had 90% power to support the hypothesis that true RR was ≥70%, and 5% significance to deny the hypothesis that true RR was ≤30%. Assuming an inevaluality rate ≤15%, we projected an accrual of 16 patients. Results: From Nov. 2004 to Jan. 2006, EGFR gene mutations were analyzed in tumor specimens from 82 patients. Twenty patients (24%) had EGFR gene mutations (16 with deletions in or near E746-A750, 4 with L858R). While there were no significant differences between mutation status and age, sex, histology, or the procedures to obtain tumor specimens, EGFR gene mutations were more frequently observed in never-smokers than in smokers (39% vs. 11%, p<0.01). Sixteen patients (median age, 68; male/female, 3/13; adenocarcinoma/SCC, 15/1; current/former/never smoker, 2/1/13) were enrolled and treated with gefitinib. To date, best response is 2 CR, 7 PR, 1 SD and 1 PD (RR, 82%). Two patients had grade 3 toxicities, including 1 skin eruption and 1 liver dysfunction. One patient had grade 1 interstitial lung disease, leading to the termination of gefitinib treatment. Conclusions: Gefitinib is very active and well tolerated as a first-line therapy for advanced NSCLCs with EGFR gene mutations. No significant financial relationships to disclose.

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.

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