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387MO - Tumour mutation profiles and circulating tumour cells in metastatic colorectal cancer patients treated with FOLFIRI + cetuximab: A prospective ancillary study of the UNICANCER PRODIGE-28 trial
- Hélène Blons (Paris, France)
Abstract
Background
We investigated the prognostic and predictive values of tumour mutation profiles determined by next-generation sequencing (NGS) and circulating tumour cell (CTC) detection.
Methods
RAS wild-type (wt) unresectable metastatic colorectal cancer (mCRC) patients (pts) with controlled disease after FOLFIRI + cetuximab (8 cycles) were randomized to receive maintenance with bi-weekly cetuximab alone or observation until disease progression. Tumour samples were centrally analysed by NGS using the AmpliSeq™ Colon and Lung Panel v2 and CTC (Cellsearch®) were assessed at baseline and during therapy. Mutation profiles and CTC counts were analysed according to objective response rate (ORR) before randomisation and progression-free survival (PFS) from randomization (in the ITT1 and the ITT2 population, respectively).
Results
A total of 214 pts (ITT1) were included in the PRODIGE28 trial according to
Conclusions
This exploratory analysis suggests that patients with any tumour mutation in MAPK pathway genes are not good candidates for maintenance treatment with cetuximab or treatment interruption after first-line FOLFIRI-cetuximab.
Clinical trial identification
NCT02404935.
Legal entity responsible for the study
UNICANCER.
Funding
Merck Serono S.A.S.
Disclosure
H. Blons: Financial Interests, Personal, Training: AstraZeneca; BMS; MSD. E. Francois: Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Roche; Financial Interests, Personal, Other, honoraria, travel, accomodations, expenses: Servier; Financial Interests, Personal, Other, honoraria: MSD; Financial Interests, Personal, Other, honoraria: Novartis; Financial Interests, Personal, Other, honoraria: Amgen. M. Ben Abdelghani: Financial Interests, Personal, Other, consulting, expert testimony, travel, accomodations, expenses: Servier; Sanofi; Bayer; Financial Interests, Personal, Other, expert testimony, travel, accomodations, expenses: Roche; Ipsen; Amgen. J.M. Phelip: Financial Interests, Personal and Institutional, Other, consulting, honoraria, research funding, travel, accomodations, expenses: Merck; Roche; Sanofi; Bayer; Financial Interests, Personal, Other, consulting, honoraria, travel, accomodations, expenses: Amgen; MSD; Pierre Fabre; Servier. S. Garinet: Financial Interests, Personal, Training: Boehringer; Financial Interests, Personal, Advisory Board: Lilly. S. Gourgou: Financial Interests, Personal, Other, methodological support: Celgene; Financial Interests, Personal, Training: Roche. O. Bouche: Financial Interests, Personal, Other, honoraria as a speaker and/or in an advisory role: Merck KgaA; Roche Genentech; Bayer; Grunenthal; AstraZeneca; MSD; Amgen; Servier; Pierre Fabre. V. Boige: Financial Interests, Personal and Institutional, Other, clinical research, scientific works, consulting, travel, accomodations, expenses: Merck; Financial Interests, Personal, Other, consulting, training, travel, accomodations, expenses: Sanofi Genzyme; Bayer; Roche; Financial Interests, Personal, Other, consulting: Ipsen; Eisai; BMS; Daiichi Sankyo; Prestizia; Financial Interests, Personal, Training: Novartis; Financial Interests, Personal, Training: MSD; Financial Interests, Personal, Other, training, travel, accomodations, expenses: Amgen. All other authors have declared no conflicts of interest.
388MO - Tumor budding, an important prognostic factor in stage III colon cancer patients treated with oxaliplatin-based chemotherapy
- Debora Basile (Vicenza, Italy)
Abstract
Background
Histological growth characteristics at the invasive front may reflect tumor aggressiveness. Specifically, tumor budding (TB), defined as single cancer cells or cluster comprising less than five cells and representing the dynamic process of epithelial-mesenchymal transition, is listed among prognostic markers in colon cancer (CC). However, its use for a better disease stratification needs to be further explored. Its prognostic role was thus evaluated in a phase III trial investigating 3
Methods
TB was evaluated on scanned hematoxylin and eosin-stained slides and scored by central review according to the criteria adopted by the 2016 International Tumor Budding consensus Conference (ITBCC2016) (number of buds per 0.785 mm2 in the hotspot), as Bd1 (0-4: low), Bd2 (5-9: intermediate), and Bd3 (≥10: high). Prediction of disease-free survival (DFS) and overall survival (OS) was analyzed by log-rank test. Clinico-pathologic features including vascular and perineural invasion, as well as tumor deposit, were associated with Bd category.
Results
Samples of 1048 CC patients were analyzed. Bd1, Bd2 and Bd3 were observed in 39%, 28% and 33%, respectively. Bd2 and Bd3 were associated with vascular and perineural invasions (p<0.005). No association was observed with tumor deposits or T/N risk groups. Bd category was significantly associated with DFS (1 vs 2-3: p=0.0008) and OS (1 vs 2-3: p=0.0015) with 3-year DFS rates of 79.5% vs 67.2% and 5-year OS rates were 89.2% vs 80.8% for Bd1 and Bd2-3, respectively. This prognostic role was confirmed in multivariable analysis adjusted on age, gender, risk group (low: T1-3/N1, high: T4 and/or N2), tumor grade, obstruction/perforation and treatment duration (3 vs 6months) for DFS (HR: 1.421; 95% CI:1.128-1.791, p=0.0029) and OS (HR: 1.627; 95% CI:1.203-2.200, p=0.0016).
Conclusions
In this large series from a randomized phase III trial, TB is an independent prognostic factor for OS and DFS in stage III CC patients treated with oxaliplatin-based standard adjuvant therapy. TB, adopted in the UICC TNM classification, should now be mandatory in every pathology report concerning patients resected from a stage III CC.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Emile: Financial Interests, Other, Honoraria: Roche; GlaxoSmithKline. C. Toullec: Financial Interests, Personal, Other, Honoraria: Merck-Serono; Sanofi; MSD; Ipsen; Amgen; Servier; BMS. J. Bennouna: Financial Interests, Personal, Other, Honoraria: Roche; Boehringer Ingelheim; Servier; AstraZeneca; MSD; Bristol Myers; Novartis; Financial Interests, Personal, Advisory Role: MSD; Roche; Boehringer; Bristol Myers Squibb; Servier; AstraZeneca; Novartis; Financial Interests, Personal and Institutional, Funding: Merck Sharp & Dohme Corp. C. Louvet: Financial Interests, Personal, Advisory Role: Merck; Roche; Servier; Amgen; Financial Interests, Personal, Other, Travel accommodation: Roche; Financial Interests, Personal, Other, Travel accommodation: Merck. T. André: Financial Interests, Other, Honoraria: Roche/Genentech; Bristol-Myers Squibb; Servier; Sanofi; Bayer; Amgen; Pierre Fabre; Vantana; GlaxoSmithKline; Financial Interests, Advisory Role: Amgen; Bristol-Myers Squibb; HalioDX; MSD Oncology; Servier; Bayer; AstraZeneca; Tesaro; Clovis Oncology; GIC Advice; Pierre Fabre; GamaMabs Pharma SA; Financial Interests, Other, Travel, Accommodations, Expenses: Roche/Genentech; Amgen; Bristol-Myers Squibb; MSD; Vantana. J. Taieb: Financial Interests, Advisory Role: Roche; Merck KGaA; Amgen; Celgene; Lilly; Servier; Sirtex Medical; MSD; Pierre Fabre; Financial Interests, Speaker’s Bureau: Servier; Amgen; Roche/Genentech; Sanofi; Merck; Lilly; MSD; Pierre Fabre. M. Svrcek: Financial Interests, Advisory Role: Bristol-Myers Squibb; Astellas; MSD; Sanofi; Financial Interests, Other, Travel, accomodations, expenses: Bristol-Myers Squibb; Ventana/Roche. All other authors have declared no conflicts of interest.
389MO - Risk of bowel obstruction in patients undergoing neoadjuvant chemotherapy for high-risk colon cancer: A nested case-control matched analysis of an international, multi-centre, randomised controlled trial (FOxTROT)
- James Glasbey (Birmingham, United Kingdom)
Abstract
Background
Global implementation of neoadjuvant chemotherapy (NAC) for colon cancer, informed by the FOxTROT trial, may increase risk of bowel obstruction. This study aims to inform patient selection for NAC.
Methods
A case-control study, nested within an international randomised controlled trial (FOxTROT. ClinicalTrials.gov:
Results
Of 1053 patients randomised in FOxTROT, 699 received NAC, of whom 30 (4.3%) developed obstruction. There was more open surgery (65.4% versus 38.0%, p=0.01) and a higher pR1 rate in obstructed patients (12.0% versus 3.8%, p=0.004), but otherwise comparable postoperative outcomes. In the case-control matched Bayesian model, two independent risk criteria were identified: (1) obstructing disease on endoscopy and/or being unable to pass through the tumour (adjusted odds ratio: 9.09, 95% credible interval: 2.34-39.66) and stricturing disease on radiology or endoscopy (OR: 7.18, 95% C.I.: 1.84-32.34). Three risk groups were defined according to the presence or absence of these criteria: 63.4% (443/698) of patients were at very low risk (<1%), 30.7% (214/698) at low risk (<10%), and 5.9% (41/698) at high risk (>10%).
Conclusions
Safe selection for NAC for colon cancer can be informed by using two features that are available before treatment initiation and identify a small number of patients with high risk of preoperative obstruction.
Clinical trial identification
NCT00647530.
Legal entity responsible for the study
Birmingham Clinical Trials Unit, University of Birmingham.
Funding
FOxTROT is funded by Cancer Research UK. Additional support was provided by the Birmingham and Leeds Experimental Cancer Medicine Centres (ECMC) network, Royal College of Surgeons of England and Rosetrees Trust, and the Swedish Cancer Society.
Disclosure
All authors have declared no conflicts of interest.
Discussion 387MO, 388MO and 389MO
- Gunnar Folprecht (Dresden, Germany)
- Clara Montagut Viladot (Barcelona, Spain)
390MO - Colorectal (CRC) cancer screening and diagnosis during the COVID-19 pandemic in Quebec, Canada
- Mustapha Tehfe (Montreal, Canada)
Abstract
Background
CRC, 3rd most common cancer in Quebec, is the 2nd and 3rd cause of cancer related death in men and women respectively. This study aimed to assess how the provincial screening program and CRC diagnosis were disrupted during the COVID-19 pandemic.
Methods
Ministry of Health of Quebec data related to cancer screening programs and diagnosis during the periods of March 2019 to February 2020 and March 2020 to February 2021 were recently reported (ISBN: 978-2-550-888379-1). We analyzed and compared the data related to Fecal Occult Blood Test (FOBT), colonoscopy, and CRC surgery rates for two comparative 4-month periods (April to July).
Results
Status of public health emergency was declared in Quebec on March 16, 2020. All elective procedures were therefore suspended on that date. From April to July 2020, FOBT decreased by 67.26%, colonoscopy procedures by 57.8% and CRC surgery by 29.5% compared to the same period from 2019. Peak of suspension of these activities was reached in April and May 2020. The waiting list for colon endoscopy increased by 210% from April to July 2020 and by 141% from August to October 2020. After the first pandemic wave, from August to October 2020, activities were resumed, colonoscopies were 11.4% less by comparison to the same period in 2019 (57 887 vs 65 326 procedures respectively). Primary CRC surgery procedures done between April and July 2020 were 29.5% less compared to the same period in 2019. For the whole year from March 2020 to February 2021, 21% less CRC resections were done compared to the year March 2019 – February 2020. The waiting list for surgery was reduced by 30% from April to July 2020 most probably because of a lower surgical referral.
Conclusions
The COVID-19 affected screening and lead to decreased CRC diagnosis rate. Even with the recovery to pre-pandemic activities, catching up with the delays is a challenge for health authorities. The impact of the offloading of diagnostic and surgical activities on cancer mortality is hard to be estimated but is likely to be significant.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
391MO - Impact of diabetes and metformin use on recurrence and outcome in early colon cancer (CC) patients: A pooled analysis of 3 adjuvant trials
- Elisabeth S. Bergen (Vienna, Austria)
Abstract
Background
Obesity and diabetes mellitus type 2 are associated with an increased risk of colorectal cancer. Recent studies have suggested beneficial effects of metformin in patients with cancer and diabetes. We sought to investigate the impact of metformin on recurrence and survival in a large, pooled analysis of non-metastatic colon cancer (CC) patients.
Methods
A patient-level meta-analysis from three randomized adjuvant trials was performed
Results
5922 patients were available for this analysis with a median follow-up of 6.8 years. 621 of 5922 patients (10.5%) had diabetes at the time of their diagnosis of CC. Of those with diabetes, 327 (52.7%) were defined as metformin-users and 294 patients (47.3%) as non-metformin-users. As expected, baseline characteristics associated with diabetes differed between non-diabetic, metformin-diabetic and non-metformin-diabetic CC patients whereas tumor-related characteristics were shown to be well balanced. CC patients with diabetes had a significantly shorter median TTR (adjHR: 1.21; 95% CI, 1.03 to 1.42;
Conclusions
CC patients with diabetes type 2 had a significantly worse survival as well as shorter TTR. Furthermore, our data suggest that metformin may attenuate the detrimental effect of diabetes on CC patient outcomes.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Discussion 390MO and 391MO
- Astrid Lièvre (Rennes, France)