ESMO Supporter 2018

Displaying One Session

ICM - Room 14b Poster Discussion session
Date
21.10.2018
Time
16:45 - 17:45
Location
ICM - Room 14b
Chairs
  • Silvia Marsoni (Candiolo, IT)
  • Richard A. Adams (Cardiff, GB)
Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

Session DOI

Lecture Time
16:45 - 16:45
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45
Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

456PD - Serial circulating tumor DNA analysis for detection of residual disease, assessment of adjuvant therapy efficacy and for early recurrence detection in colorectal cancer

Presentation Number
456PD
Lecture Time
16:45 - 16:45
Speakers
  • Thomas Reinert (Aarhus, DK)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Early detection of disease recurrence has been shown to improve survival in patients with colorectal cancer (CRC). Previous studies have analyzed circulating tumor DNA (ctDNA) to monitor tumor burden in CRC using small gene panels and ddPCR. Here, we use a personalized multiplex-PCR and NGS platform (SignateraTM RUO) to detect ctDNA in serially collected plasma samples to assess if ctDNA detection defines the subset of patients with high risk of recurrence both before and after adjuvant chemotherapy (ACT).

Methods

A cohort of 130 patients with stage I–IV CRC, treated according to standard of care was analyzed. For each patient, tumor-specific panels of 16 mutations were designed using somatic mutation signatures obtained from WES. Plasma samples (n = 829) collected pre- and post-surgery, and during ACT were analyzed. Recurrence-free survival was calculated for patients stratified by ctDNA status post-surgery (n = 91) and post-ACT (n = 58).

Results

ctDNA status after surgery, but prior to ACT, was assessed in 91 patients. Relapse was observed for 75% (6/8) of the ctDNA+, and only for 13% (11/83) of the ctDNA- patients. Effective ACT treatment was observed for 30% (3/10) of the post-operative ctDNA+ patients. These were consistently ctDNA- in post-ACT serially collected blood samples, and concordantly relapse free at end of follow-up. ctDNA status post-ACT was assessed in 58 patients. Radiologically confirmed relapse was observed for 77% (10/13) of the ctDNA+ and for 4% (2/45) of ctDNA- patients. On average ctDNA detected relapse 9.13 months earlier than standard-of-care CT-imaging.

Conclusions

Serial post-operative ctDNA analysis enables stratification of patients into high or low recurrence risk subgroups, assessment of ACT treatment efficacy, and early detection of recurrence. Importantly, it also indicates that ACT can eliminate residual disease in up to 30% of the post-operative ctDNA+ patients and therefore can be a treatment option for ctDNA+ patients. In summary, ctDNA analysis has great potential to guide treatment decisions, both in the adjuvant and post-adjuvant settings.

Legal entity responsible for the study

Claus Lindbjerg Andersen.

Funding

Natera Inc, San Carlos, California.

Disclosure

H. Sethi, R. Salari, S. Shchegrova, R. Swenerton, H-T. Wu, S. Sharma, P. Natarajan, S. Dashner, T. Tin, A. Olson, H. Pawar, B. Zimmermann, J. Lin: Employees: Natera, Inc., and own stock, or options to stock in the company. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

457PD - Kinase Fusions in Colorectal Cancers: A Unique Biologic Subset

Presentation Number
457PD
Lecture Time
16:45 - 16:45
Speakers
  • Russell Madison (Cambridge, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

In a subset of colorectal carcinomas (CRC), fusion genes resulting from genomic rearrangements of protein kinases have been previously reported. Anecdotal responses to matched therapy support clinical relevance but larger description is lacking.

Methods

18,407 tissue specimens and 513 ctDNA specimens from patients with CRC were assayed using hybrid-capture based comprehensive genomic profiling (CGP) of 63, 186, or 315 genes plus introns from 6, 14 or 28 genes commonly rearranged in cancer. Tumor mutational burden (TMB) was assessed on solid tumor cases on 0.83 or 1.1 Mb of DNA and is reported as mutations per megabase (m/mb). Microsatellite instability (MSI) was assessed across 114 homopolymeric loci.

Results

Kinase rearrangements (KRE) were identified in 126 CRC tissue specimens (0.68%) and 7 CRC ctDNA samples (1.36%). The most frequently altered kinases were RET (22%), BRAF (22%), NTRK1 (16%), and ALK (13%). KRE of EGFR, FGFR3, FGFR1, ROS1, RAF1, FGFR2, NTRK3, PDGFRB, MET, and NTRK2 occurred in 5 or less cases each. Patients with tumors harboring KRE were 52% female (69/133) and had a median age of 62 years. Among cases with KRE, the non-kinase genes most frequently altered were TP53 (67.7%), APC (39.1%), RNF43 (30.1%), and MLL2 (21.1%), and KRAS was wildtype in 90% of these cases. Cases with KRE had a median TMB of 6.96 m/mb, relative to a median TMB of 3.60 m/mb for all CRC cases in the database. Of cases assessed for MSI status, 38% (41/107) were MSI high with a median TMB of 42.8 m/mb (range 20.9-118.3 m/mb). Of all KRE cases, NTRK1 and RET KRE cases were 86% and 45% MSI high, respectively. MSI Status by Kinase.

KinaseTotalMSI StatusCases% MSI-H
ALK14MSI-H214.29%
MSS12
BRAF23MSI-H417.39%
MSI-L1
MSS18
FGFR23MSI-H3100.00%
NTRK122MSI-H1986.36%
MSS3
NTRK33MSI-H3100.00%
RET22MSI-H1045.45%
MSS12

Conclusions

Among KRE CRC, the enrichment of MSI high status in NTRK1 KRE cases, and to a lesser extent RET, FGFR2, and NTRK2, suggests these patients may benefit from both TKIs and checkpoint inhibitors either as respective monotherapies or in combination. No MS stable KRE cases had high TMB, suggesting further investigation of the observed intersection of MSI-high and KRE is warranted as a unique biologic subset.

Legal entity responsible for the study

Foundation Medicine Inc.

Funding

Foundation Medicine Inc.

Disclosure

R. Madison, L. Juckett, J. Chung, L.A. Albacker, V.A. Miller, A.B. Schrock, J.S. Ross, S.M. Ali: Employee, Equity interest: FMI. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

LBA24 - A Multi-Omic Analysis for Prospective Patient Stratification in Localised Colorectal Cancer (CRC).

Presentation Number
LBA24
Lecture Time
16:45 - 16:45
Speakers
  • Noelia Tarazona Llavero (Valencia, ES)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Early stage CRC is highly heterogeneous at multiple molecular levels. However, microsatellite instability (MSI) is the only recommended biomarker to risk stratify patients (stage II). New biomarkers and clinically-applicable assays are highly necessary. These require thorough biological understanding and prospective validation for real-time application.

Methods

Stage I-III CRC patients were prospectively recruited at the INCLIVA Institute (Valencia) in collaboration with the Institute of Cancer Research (London). Clinicopathological features (such as stage, grade, sidedness, MSI, CDX2 expression, vascular/perineural invasion, Neu/Lymph ratio (NLR) and platelets/lymph (PLR)) were collected. DNA and RNA extracted from FFPE samples were assessed with a custom 29 frequently mutated CRC gene-panel (NGS) and a validated CRCAssigner/CMS subtyping assay (NanoCRC – NanoString Technologies). Plasma-based prometastatic cytokines (IL-6, IL-11, TGF-b) were measured (ELISA). Fisher’s exact test, Kruskal-Wallis and Mann Whitney tests were used for categorical/non categorical variables.

Results

A total of 119 patients with known clinical variables were available for subtypes, mutational profile and cytokines levels analysis. NanoCRC subtypes demonstrated known significant association (p<0.05) with clinical and mutational features (CMS1 and right side, MSI high; CMS3 and RAS mutation) and newly observed significant association with CDX2 expression (low in CMS1), CTNNB1 mutation (enriched in CMS3), vascular/perineural invasion (high in mesenchymal subtypes CMS1 and 4). Between cytokines, high IL-6 levels were significantly associated (p<0.05) with CMS subtypes (high in CMS1) BRAF mutation, right sidedness, MSI status, high grade, vascular invasion, high NLR and PLR. After 18.7 months of median follow-up, disease relapse was observed in 10 patients. A multivariable analysis confirmed stage, low CDX2, vascular/perineural invasion significantly associated with relapse and borderline significance for CMS4.

Conclusions

LBs response-based multi-omics profiles identify diverse risk groups, predict response to adjuvant therapy and may ultimately lead to a personalised approach for early CRC.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

458PD - Causal modeling of CALGB/SWOG 80405 (Alliance) identifies primary (1_) side-related angiogenic drivers of metastatic colorectal cancer (mCRC)

Presentation Number
458PD
Lecture Time
16:45 - 16:45
Speakers
  • Rahul K. Das (Cambridge, MA, US)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Patients (pts) in 80405 w/ mCRC originating from left-sided (L) 1° tumor had superior OS and PFS vs. pts w/ right-sided (R) 1°, but the underlying biological explanation is mostly unknown. We applied causal machine learning methods to the study to discover molecular pathways linking 1° side to OS and PFS.

Methods

430 pts including 128 RAS mutant (mut) had clinical data, mut status in 10 genes, MSI status, gene expression from 816 genes by Nanostring, and consensus molecular subtypes (CMS). For this analysis, transverse included w/ R-sided tumors. Using a Bayesian causal machine learning platform, we built an ensemble of network models for OS and PFS.

Results

Bayesian networks revealed a molecular pathway downstream of 1° side and driving OS and PFS: MSI-H status, BRAF mut, and extracellular matrix remodeling and angiogenesis-related genes including EGF7A, ALOX5, VIM, MAP4K1, COL10A1, COL6A3, and COL5A2. BRAF mut and angiogenesis signature are prognostic for OS and PFS and downstream of 1° side (Table); angiogenesis signature is downstream of BRAF (OR 13.1, p < 0.001). CMS4 and RAS mut are prognostic for OS and PFS but not causally downstream of 1° side. In angiogenesis-high pts (n = 90), 1° side is no longer prognostic for OS or PFS. In angiogenesis-low pts, 1° side remains prognostic only for OS. There is a significant angiogenesis by biologic interaction for OS (p = 0.008) favoring bevacizumab in angiogenesis-high pts.

R vs LOS
PFS
OR (p-value)HR (95% CI)p-valueHR (95% CI)p-value
RAS1.7 (0.01)1.42 (1.14-1.77)0.0021.24 (1.00-1.54)0.048
CMS41.2 (0.5)1.68 (1.33-2.13)<0.0011.60 (1.28-2.01)<0.001
angio sig.3.9 (<0.001)1.71 (1.32-2.21)<0.0011.71 (1.34-2.19)<0.001
BRAF7.7 (<0.001)1.76 (1.28-2.40)<0.0011.57 (1.16-2.12)0.003
R vs L (all)-1.50 (1.22-1.86)<0.0011.24 (1.02-1.51)0.03
R vs l (angio +)-1.26 (0.76-2.08)0.361.15 (0.72-1.82)0.56
R vs L (angio -)-1.47 (1.15-1.88)0.0021.15 (0.91-1.44)0.23

Conclusions

Impact of 1° side on OS and PFS is associated with BRAF and angiogenesis-related pathways, consistent with the relative clinical benefit of anti-VEGF therapy in R-sided and BRAF mut pts.

Clinical trial identification

NCT00265850.

Legal entity responsible for the study

Alliance for Clinical Trials in Oncology.

Funding

U10CA180821, U10CA180882, U10CA180830, U10CA180888; Eli Lilly and Company, Genentech, Pfizer.

Disclosure

R.K. Das, L. Furchtgott, B. Hayete, B. Harms, D. Cunha, J. Latourelle, D. Wuest, I. Khalil, C. Washburn: Employee: GNS Healthcare. K. Rich: Consulting: GNS Healthcare. A. Nixon: Research funding: Seattle Genetics, Tracon Pharma, Amgen, Novartis, Genentech/Roche, Acceleron, MedPacto, Leadiant Biosciences; Consultant: Pfizer, Eli Lilly. H-J. Lenz: Advisory board, lectures: BMS, Bayer, Roche, Merck Serono, Genentech. A. Venook: Research funding: Genentech, Roche, Merck. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

Invited Discussant 456PD, 457PD, LBA24 and 458PD

Lecture Time
16:45 - 17:00
Speakers
  • Silvia Marsoni (Candiolo, IT)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45
Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

Q&A led by Discussant

Lecture Time
17:00 - 17:15
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45
Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

459PD - Long-term Results of Postoperative Chemoradiation Therapy With Capecitabine and Oxaliplatin Versus Capecitabine Alone for Locally Advanced Rectal Cancer: A Randomized, Multicenter, Phase 3 Trial

Presentation Number
459PD
Lecture Time
17:15 - 17:15
Speakers
  • Ning Li (Beijing, CN)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Postoperative radiotherapy is still recommended for stage II/III rectal cancer after defnitive surgery who did not receive preoperative chemoradiotherapy. This phase III study aims to explore the role of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy for stage II/III rectal cancer.

Methods

Patients with pathologically confirmed stage II/III rectal cancer were randomized (1:1) to either radiotherapy with concurrent capecitabine (Cap-RT group) or with capecitabine and oxaliplatin (Capox-RT group). Radiotherapy consisted of 45-50.4 Gy in 25-28 fractions. In the Cap-RT group, concurrent chemotherapy consisted of two cycles of oral capecitabine (1,600 mg/m2) on days 1–14 and 22–35. The Capox-RT group received radiotherapy concurrent with oral capecitabine (1,300 mg/m2) on days 1–14 and 22–35, and a 2-h infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Following 4 weeks of completing chemoradiation, 4-12 cycles of fluorouracil based adjuvant chemotherapy was delivered. The primary endpoint was 3-year disease-free survival rate (DFS).

Results

Between April 1, 2008 and September 30, 2015, we enrolled 589 participants from nine centers in China. Of these participants recruited, 294 were in the Cap-RT group and 295 in the Capox-RT group. Baseline characteristics were well balanced between two groups. The 3-year and 5-year DFS rate was 73.7% and 69.7% in the Capox-RT group and 76.1% and 71.2% in the Cap-RT group (p = 0.546), respectively. No significant difference was observed in overall survival, cumulative incidence of local recurrence or distant metastasis between two groups (p > 0.05). More grade 3-4 acute toxicity was observed in the Capox-RT group than in the Cap-RT group, but not significantly (47.1% vs. 39.5%, p = 0.065). In N2 subgroup analysis, DFS rate in Capox-RT group was significantly higher than Cap-RT group (p = 0.045).

Conclusions

In stage II/III rectal cancer, either radiotherapy with concurrent capecitabine or capecitabine and oxaliplatin are equally beneficial in long-term survival. N2 subsets of patients may benefit from intensive concurrent chemotherapy regimen.

Clinical trial identification

NCT00714077.

Legal entity responsible for the study

Jing Jin.

Funding

Chinese National Nature Science Funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

460PD - The value of chemotherapy in Stage II colon cancer: much less than we thought

Presentation Number
460PD
Lecture Time
17:15 - 17:15
Speakers
  • Lunpo Wu (Hangzhou, CN)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

The use of adjuvant chemotherapy in stage II colon cancer patients remains controversial. We sought to evaluate the real effectiveness of chemotherapy on stage II colon cancer as well as select suitable patients for additional treatment.

Methods

Patients with stage II colon cancer during 1988 to 2010 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. The competing-risk survival regression model and propensity score matching method were used to evaluate the colon cancer specific death (CCSD) and non-CCSD. Also, in order to identify more suitable candidates for chemotherapy, a competing-risk nomogram model was constructed. Risk score (RS) was calculated according to the model.

Results

53,617 patients with stage II cancer were included, 25.92% have received chemotherapy, and 74.08% were without chemotherapy. In total, 19.56% and 23.99% of patients died of CCSD and non-CCSD, respectively. Univariate and multivariate analyses showed receiving chemotherapy appears to be associated with more CCSD and less non-CCSD (HR 1.19, 95%CI1.14-1.24; HR 0.57, 95%CI 0.54-0.60, respectively), even after adjustment for covariates and propensity score weighting. A competing-risk nomogram was established and the model was relatively good with a C-index of 0.661. Based on the RS, different risk stage could only predict prognosis but fail to predict the benefit from chemotherapy.

Conclusions

No survival benefit was observed for patients with stage II cancer with chemotherapy. The value of chemotherapy is much less than we thought. Chemotherapy will not increase the treatment-related mortality.

Legal entity responsible for the study

Second Affiliated Hospital of Zhejiang University School of Medicine.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

461PD - Folfox and intra-arterial DEBIRI as front-line treatment in patients with non resectable colorectal cancer liver metastases (FFCD 1201 phase II trial)

Presentation Number
461PD
Lecture Time
17:15 - 17:15
Speakers
  • Simon Pernot (Paris, FR)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Chemoembolization with Drug-eluting beads loaded with Irinotecan (DEBIRI) increased overall survival in a small randomized phase III study, as compared with intra-venous chemotherapy, in heavily pretreated patients (pts) with liver-dominant metastases from colorectal cancer (LMCRC). First line DEBIRI in combination with systemic chemotherapy may show interesting results in terms of survival, local control and secondary resection rate.

Methods

FFCD 1201 is a single-arm, open-labelled phase II study. Pts with LMCRC received mFOLFOX6 with hepatic intra-arterial DEBIRI. In case of bilobar disease, 4 courses of DEBIRI were performed with 100mg of irinotecan, every 2 weeks, alternating right and left lobe, or 2 sessions with 200mg with both lobes treated during the same session. Eligibility criteria included no prior CT for metastatic disease, non-resectable liver-dominant disease, liver involvement < 60%, adequate organ function, age ≥ 18 years, PS ≤ 2. The primary endpoint was progression-free survival (PFS) rate at 9 months (m) (Fleming design, H0: 55%, H1: 75%).

Results

57 pts were enrolled with a median age of 63 years (44 to 78); PS 0-1 95%; median number of LM 9.5 (1 to 20). 49% of pts received the full planned intra-arterial cycles and 87.5% at least 50% of the planned treatment. Main grade 3-4 toxicities were neutropenia (24.6%), diarrhea (12.3%), abdominal pain (10.5%), and pancreatitis/cholecystitis (8.8%/5.3%). One toxic death occurred. PFS rate at 9 m was 53.6% (95% CI, 41.8% - 65.1%). Disease control rate (RECIST) was 92.8% (complete response 3.6%, partial response 69.6%, stable disease 19.6%). Tumor shrinkage > 20% occurred in 85.7% of pts, with a median depth of response of -47% (-100% to + 38%). After FOLFOX + DEBIRI, 19 pts (33%) had a R0 surgery +/- ablative therapy. With a median follow-up of 27.5 m (95% CI, 21.0 - 30.6), median OS was 33.1 m (95% CI, 25.7 ; 46.1) and median PFS 10.8 m (95% CI, 8.18 ; 12.32).

Conclusions

Despite the primary endpoint was not met, front-line DEBIRI + FOLFOX without any targeted agent allow an excellent disease control rate in non-resectable LMCRC with deep responses, leading to secondary resection in 1/3 of pts.

Clinical trial identification

NCT01839877.

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

Biocompatibles (BTG).

Disclosure

S. Pernot: Honoraria: Amgen; Consulting or advisory, travel, accommodations, expenses: Amgen, Merck. P. Artru: Honoraria: Roche, Amgen, Bayer, Servier, Lilly, Merck; Consulting or advisory role: Roche, Merck; Speaker's bureau: Roche, Merck, Servier; Travel, accommodations, expenses: Roche, Merck, Bayer. D. Tougeron: Consulting, advisory role: Amgen, Sanofi, Merck Serono, Bristol-Myers Squibb, MSD; Travel, accommodations, expenses: Sanofi, Amgen; Honoraria: Amgen, Roche, Novartis, Sanofi, Bristol-Myers Squibb, Merck Serono, MSD. C. De La Fouchardière: Consulting, Advisory role: Lilly, Roche, Bayer, Shire, Amgen; Travel, accommodations, expenses: Roche, Celgene, Amgen; Research funding: Roche. J-L. Raoul: Consulting or advisory role: Bayer Schering Pharma, Taiho Pharmaceutical, BTG; Research funding: Celgene Honoraria: Bayer, Taiho Pharmaceutical, Merck Serono. L. Dahan: Honoraria: Sanofi, Amgen. R. Guimbaud: Travel, accommodations, expenses: Merck Serono, Roche. P. Michel: Travel, accommodations, expenses: Lilly, Merck, Bayer, Hospira. O. Pellerin: Consulting or advisory role: Terumo; Travel, accommodations, expenses: Gore; Research Funding: B. Braun. J. Taieb: Consulting or advisory role: Roche, Merck KGaA, Amgen, Celgene, Lilly, Baxalta, Servier, Sirtex Medical; Speaker's bureau: Servier, Amgen, Baxalta, Roche/Genentech, Sanofi, Merck, Lilly. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

462PD - Postoperative carcinoembryonic antigen (CEA) association with survival and oxaliplatin benefit in stage II colon cancer (CC): post hoc analysis of the MOSAIC trial.

Presentation Number
462PD
Lecture Time
17:15 - 17:15
Speakers
  • Edouard Auclin (Paris, FR)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45

Abstract

Background

Adjuvant chemotherapy (LV5FU2 +/- oxaliplatin) is recommended for high risk (T4 and/or bowel perforation and/or number of nodes examined <10) stage II CC. After curative treatment (ttt), CEA measurement is recommended for follow up. CEA above 5 ng/mL is of poor prognosis, however recently a cut-off of 2.35 was shown to be more appropriate, in a cohort of 40,000 patients (pts). We explored the postoperative CEA prognostic value and its predictive value for the benefit of oxaliplatin addition to LV5FU2 adjuvant chemotherapy.

Methods

Stage II CC pts in MOSAIC study with postoperative CEA available were included. Overall (OS) and Disease Free Survival (DFS) were estimated with the Kaplan Meier method. CEA predictive value for benefit of oxaliplatin addition to LV5FU2 on survival was evaluated with an interaction term between treatment and CEA risk group in the Cox model, firstly in the whole stage II population, then according to high/low risk groups.

Results

CEA was available in 867 pts (96.4%), with n = 664 ≤ 2.35 (group 1) and n = 203 > 2.35 (group 2). 3y OS rates were 96%, and 90% in groups 1 and 2, p = 0.02. 3y DFS rates were 88%, and 79%, p = 0.006. There was an interaction between CEA level and ttt arm (LV5FU2 or FOLFOX) for OS (interaction term p = 0.03) and DFS (p = 0.11), Table. This was confirmed in high risk (interaction term p = 0.03 and 0.09, for OS and DFS) but not in low risk stage II CC (p = 1 and 0.78 for OS and DFS), Table. CEA was associated with an improvement of oxaliplatin benefit in OS and DFS in high risk stage II CC pts.

3y OS and DFS in the MOSAIC stage II pts according to postoperative CEA level and ttt arm

3y OS %
3y DFS %
LV5FU2FOLFOXLV5FU2FOLFOX
Whole populationCEA ≤2.35 ng/mL97.393.988.288.7
>2.3588.492.576.081.1
Low riskCEA ≤2.35ng/mL98.895.791.891.5
>2.3590.391.478.675.8
High riskCEA ≤2.35 ng/mL95.592.584.086.3
>2.3587.093.674.087.2

Conclusions

We validated that postoperative CEA with a CEA cut-off of 2.35 ng/mL was prognostic for OS and DFS in stage II CC. CEA was also predictive of oxaliplatin benefit in OS and DFS for high risk stage II CC. External validation on the CEA predictive value is ongoing and will be presented with this cohort.

Legal entity responsible for the study

Dewi Vernerey.

Funding

Has not received any funding.

Disclosure

T. Andre: Honoraria: Roche/Genentech, Bristol-Myers Squibb, Servier, xBiotech, Bayer Sanofi, Amgen, PRMA Consulting; Advisory role: Roche/Genentech, Amgen, Bristol-Myers Squibb, Mundipharma International, HalioDX, MSD Oncology, Servier, Guardant Health, Bayer. J. Taieb: Advisory role: Roche, Merck KGaA, Amgen, Lilly, Baxalta, Servier and Sirtex Medical. J. Tabernero: Advisory role: Bayer, Boehringer Ingelheim, Lilly, MSD, Merck Serono, Novartis, Roche, Sanofi, Taiho Pharmaceutical, Genentech/Roche, Merrimack, Symphonu Evolution, Peptomyc. T. Hickish: Research funding: xBiotech, Roche, Pfizer, Novartis, Merck. A. de Gramont: A. Honoraria: Yakult, Chugai Pharma. D. Vernerey: Advisory role: OSE Immunotherapeutics, Janssen-Cilag, Prestizia, HalioDX. All other authors have declared no conflicts of interest.

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Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

Invited Discussant 459PD, 460PD, 461PD and 462PD

Lecture Time
17:15 - 17:30
Speakers
  • Richard A. Adams (Cardiff, GB)
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45
Poster Discussion session - Gastrointestinal tumours, colorectal 2 Poster Discussion session

Q&A led by Discussant

Lecture Time
17:30 - 17:45
Location
ICM - Room 14b, ICM München, Munich, Germany
Date
21.10.2018
Time
16:45 - 17:45