Impact of Baseline Covariates and Prior Therapy on the Efficacy of Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

ABSTRACT Aim: Expanding RAS analyses beyond KRAS exon 2 is important in selecting patients (pts) for pmab treatment. Here we present prespecified subgroup analyses from a phase 3 randomised second-line pmab + FOLFIRI vs FOLFIRI study in metastatic colorectal cancer (mCRC) pts. Methods: Progression-free (PFS) and overall survival (OS) were co-primary endpoints. KRAS exon 2 wild-type (WT) samples were tested for mutations in KRAS exons 3/4, NRAS exons 2/3/4 and BRAF exon 15 via bidirectional Sanger sequencing and WAVE-based SURVEYOR®. PFS and OS subgroup analyses were performed by randomisation stratification factors (ECOG performance status [PS], prior bevacizumab [bev]/prior oxaliplatin [ox…

The hard road to data interpretation: 3 or 6 months of adjuvant chemotherapy for patients with stage III colon cancer?

Background Six months of adjuvant oxaliplatin-based chemotherapy is standard for patients with stage III colon cancer following surgery. However, oxaliplatin is associated with peripheral neurotoxicity which worsens over treatment duration. Consequently, a shorter treatment duration, if equally effective, would be extremely beneficial. A pooled analysis of data for 12 834 stage III colon cancer patients, from six randomised phase III trials of adjuvant therapy, the International Duration Evaluation of Adjuvant chemotherapy study, was carried out and the results presented at the ASCO Annual Meeting 2017. To clarify the potential impact of these results on clinical practice, ESMO decided to s…

Tumour Shrinkage and Response Outcomes During Second-Line Panitumumab (Pmab) + Folfiri Vs Folfiri Treatment

ABSTRACT Aim: Tumour shrinkage/response are important outcomes for patients (pts) with metastatic colorectal cancer (mCRC) as they may delay progression and ultimately improve survival. Here we report tumour response data for pts with RAS WT mCRC treated with FOLFIRI ± pmab. Methods: 181 was a phase 3 randomised study of second-line pmab + FOLFIRI vs FOLFIRI alone in pts with previously treated mCRC. KRAS exon 2 wild-type (WT) samples from this study were tested for mutations in KRAS exons 3/4 and NRAS exons 2/3/4 via bidirectional Sanger sequencing and WAVE-based SURVEYOR® to identify pts with RAS WT tumours (no mutations in KRAS/NRAS exons 2, 3 or 4). Objective response rates (ORRs) and m…

Final results from a randomized phase 3 study of FOLFIRI \pm$ panitumumab for second-line treatment of metastatic colorectal cancer

Abstract: Background: The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported. Patients and methods: Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status. Results: One thousand one hundred and eighty-six patient…

The management of metastatic pancreatic cancer: expert discussion and recommendations from the 14th ESMO/World Congress on Gastrointestinal Cancer, Barcelona, 2012

Regorafenib for previously treated metastatic colorectal cancer (mCRC): results from 683 Italian patients treated in the open-label phase IIIB CONSIGN study

ESMO consensus guidelines for the management of patients with metastatic colorectal cancer

Contains fulltext : 165965.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and speciali…

Abstract CT263: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients: The PEGASUS trial

Abstract Background: Moving stage III Colon Cancer (CC) into the precision medicine space is a priority in view of the lack of molecular markers driving adjuvant treatment. Retrospective studies have demonstrated the tremendous prognostic impact of circulating tumor DNA (ctDNA) analysis after curative intent surgery, and suggested that lack of conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy reflects treatment failure. With these premises, we have designed the PEGASUS trial (EudraCT 2019-002074-32) to prove the feasibility of using liquid biopsy to guide the post-surgical and post-adjuvant clinical management of early colon cancer patients. Methods: PEGASUS is…

Time-course evaluation of survival and treatment in FIRE-3 trial (AIO KRK0306).

3528Background: To investigate overall survival (OS) differences in FIRE-3 in context of exposure to treatments (i.e. first-, second-, third-line) in time course. Methods: We compared OS in FIRE-3 ...

Analysis of KRAS/NRAS mutations in a phase III study of panitumumab with FOLFIRI compared with FOLFIRI alone as second-line treatment for metastatic colorectal cancer

Abstract Purpose: We evaluated the influence of RAS mutation status on the treatment effect of panitumumab in a prospective–retrospective analysis of a randomized, multicenter phase III study of panitumumab plus fluorouracil, leucovorin, and irinotecan (FOLFIRI) versus FOLFIRI alone as second-line therapy in patients with metastatic colorectal cancer (mCRC; ClinicalTrials.gov, NCT0039183). Experimental Design: Outcomes were from the study's primary analysis. RAS mutations beyond KRAS exon 2 (KRAS exons 3, 4; NRAS exons 2, 3, 4; BRAF exon 15) were detected by bidirectional Sanger sequencing in wild-type KRAS exon 2 tumor specimens. Progression-free survival (PFS) and overall survival (OS) we…

KRAS/NRAS and BRAF Mutations in the 20050181 Study of Panitumumab + FOLFIRI for the 2ND-Line Treatment of Metastatic Colorectal Cancer: Updated Analysis

Updated analysis of KRAS/NRAS and BRAF mutations in study 20050181 of panitumumab (pmab) plus FOLFIRI for second-line treatment (tx) of metastatic colorectal cancer (mCRC).

3568 Background: Previously, extended RAS analysis from this study showed a trend toward improvements in HR on OS and PFS with pmab + FOLFIRI vs FOLFIRI in WT RAS group vs WT KRAS exon 2 group. Her...

Final results of study 20050181: A randomized phase III study of FOLFIRI with our without panitumumab (pmab) for the second‑line treatment (tx) of metastatic colorectal cancer (mCRC).

3535 Background: The primary analysis of study 20050181 showed that in patients (pts) with wild-type (WT) KRAS mCRC, pmab plus FOLFIRI given as second-line therapy significantly improved progression-free survival (PFS) vs FOLFIRI alone. Here, we report on a prespecified descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts with mCRC, ECOG 0-2, who had one prior fluoropyrimidine-based chemotherapy regimen were randomized 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI (Arm 2). Co-primary endpoints were OS and PFS (central assessment). Secondary endpoints included objective response rate (ORR) and safety. Tumor KRAS status was determined by a blin…

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

Contains fulltext : 111010pub.pdf (Publisher’s version ) (Closed access) Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach pe…

The PEGASUS trial: Post-surgical liquid biopsy-guided treatment of stage III and high-risk stage II colon cancer patients.

TPS4124 Background: Moving stage III Colon Cancer (CC) into the precision medicine space is a priority in view of the lack of molecular markers driving adjuvant treatment. Retrospective studies have demonstrated the tremendous prognostic impact of circulating tumor DNA (ctDNA) analysis after curative intent surgery, and suggested that lack of conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy reflects treatment failure. With these premises, we have designed the PEGASUS trial (NCT04259944). Methods: PEGASUS is a prospective multicentric study designed to prove the feasibility of using liquid biopsy (LB) to guide the post-surgical and post-adjuvant clinical manag…

Prospective validation of a lymphocyte infiltration prognostic test in stage III colon cancer patients treated with adjuvant FOLFOX.

IF 6.029; International audience; BackgroundThe prognostic value of lymphocyte infiltration (LI) of colorectal carcinoma (CC) has been demonstrated by several groups. However, no validated test is currently available for clinical practice. We previously described an automated and reproducible method for testing LI and aimed to validate it for clinical use.Patients and methodsAccording to National Institutes of Health criteria, we designed a prospective validation of this biomarker in patients included in the PETACC8 phase III study. Primary objective was to compare percentage of patients alive and without recurrence at 2 years in patients with high versus low LI (#NCT02364024). Associations…