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Place des nouveaux traitements dans les cancers colorectaux Prof Eric Raymond Chef de service d’oncologie médicale Hôpital Paris Saint-Joseph Paris 14ème

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Page 1: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Placedesnouveauxtraitementsdanslescancerscolorectaux

ProfEricRaymondChefdeserviced’oncologiemédicale

HôpitalParisSaint-JosephParis14ème

Page 2: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017
Page 3: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Nouveauxtraitementsoncologiquesdescancerscolorectaux• Priseenchargedelamaladiemétastatiquehépatique

• LetandemChimiothérapie+/- thérapieciblée+Chirurgie• Traitementintra-artérielshépatiques

• Chimiothérapiesintra-artérielles• Radio-embolisationhépatiqueàlY90• Billeschargéesàl’irinotecan(Debiri)

• Traitementsdelacarcinosepéritonéale• IPAC• PIPAC

• Immunothérapiedescancerscolorectaux

Page 4: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

LefoieNouveauxtraitementsoncologiquesdescancerscolorectaux

Page 5: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Colorectalcancer:atypicalexamplewherelivermetastasesarepotentiallycurable

•50%ofpatientswithcolorectalcancerwilleventuallydeveloplivermetastasesduringthenaturalcourseofthedisease

•25%ofpatientspresentwithlivermetastasesatthetimeofdiagnosis

Ruers T, Bleichrodt RP. Treatment of liver metastases, an update onthe possibilities and results. Eur J Cancer 2002;38:1023-1033

Page 6: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Improved survival across time for metastatic colorectal cancer

1980 1985 1990 1995 2000 2005 2010

Best supportive care

Median OS

5-FUIrinotecan

CapecitabineOxaliplatin

CetuximabBevacizumab

Panitumumab

OS

(Mos

)

30

20

10

01980 1985 1990 1995 2000 2005

Yr2010

Ziv-afliberceptRegorafenib

Page 7: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Allongement de la survie médiane

Page 8: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

80405: OS in Patients Rendered Disease Free With Systemic Therapy + Surgery

N (Events) mOS, Mos (95% CI)124 (34) 66.3 (59.8-NA)

Venook AP, et al. ASCO 2014. Abstract LBA3.

012 24 36 48 60 72

80

100

60

40

0

OS

(%)

20

84Mos

>25% long term survival

Page 9: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Resectable

BorderlineResectable

Unresectable

10-30%

70%

Distributionoflivermetastases

Page 10: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Resectable

BorderlineResectable

Unresectable

10-15%

70%

Distributionoflivermetastasesandprincipleofsystemictherapy

PREOPERATIVE DOUBLET(followed by a post-operative3 month doublet)

-Short-term duration (£6 months)

SYSTEMIC DOUBLETS

-Long-term duration (≥6 months) -Response rate 40-50%- Optimal tolerance

10-15%

Page 11: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Improve progression-free survival(Improve survival)

SurgeryPreoperative

Chemotherapy(FOLFOX)3 months

PostoperativeChemotherapy

(FOLFOX)3 months

Page 12: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Overall median survival followingliver resection: 3.6 years (1.7-7.3)

>1 liver metastases>3 cm tumor diameterSynchronousElevated CEAPoor tumor gradePositive margins

Solitary nodule<5 cm diameterMetachronous

Nordlinger et al, Ann Surg 2012Kanas et al, Clinical Epidemiol 2012

Adam et al, Ann Surg 2010

Prognosticfactorsofsurvival

Role of systemic therapy+++

Role of chemotherapy +/-Interval of relapse

Age, performance status

Page 13: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

metastases who showed different TRG between their metastaseswere categorized according to the highest TRG. The TRG were thengrouped into 3 categories: major histologic tumor response (MjHR;TRG1 and 2); partial histologic tumor response (PHR; TRG3) andabsence of histologic tumor response (NHR; TRG4 and 5). Thissystem has the advantage of being the same as the one used forprimary colorectal tumors by the American Joint Committee onCancer, TNM, and allows easy comparison of response between theprimary and the metastatic site.

A second method for assessing pathologic response in patientswith CLM was described by Blazer et al. [32]. This method alsoinvolved sectioning the hepatectomy specimen into 5 mm thickslices that were fixed onto slides and then stained with hematox-ylineeosin. In patients with multiple liver metastases, each lesionwas extensively sampled from the center to the periphery toinclude multiple sections of tumor and non-neoplastic liverparenchyma. The most viable section of the tumor nodule was usedfor sampling. Between 1 and 14 (mean 4) stained samples fromeach tumor nodule were evaluated by 2 pathologists who deter-mined the pathologic response by estimating the area of residualviable tumor cells within each metastatic nodule as a proportion ofthe total tumor surface area. No control group of untreated patientswas analyzed. The tumor area included areas of chemotherapy-related tissue injury, tumor necrosis and fibro-collagenous prolif-eration. Pathologic tumor response was categorized according towhether it met the criteria for a complete response (no residualcancer cells remaining), major (1e49% of residual cancer cellsremaining) or minor response (!50% of residual cancer cells

remaining) (Fig. 2b). The minor response group also includedpatients with no response (100% of residual cancer cells remaining).For patients with multiple tumor nodules, pathologic response wasbased on the mean of the values for all the tumor nodules.

Maru and colleagues described a third sampling method inpatients with CLM, which involved measuring tumor thickness atthe tumor-normal interface (TNI) [34]. The maximum thickness ofuninterrupted layers of tumor cells was measured perpendicular tothe TNI by two independent pathologists; for specimens containingmore than one tumor, the average tumor thickness at the TNI wascalculated. Tumor thickness was found to correlate with bothradiographic and pathologic response, with greater thickness pre-dicting shorter recurrence-free survival. To the authors’ knowledge,no direct comparison of the 3 published methods for classificationof pathologic response has been made to date, therefore a superi-ority of one of the methods cannot be estimated, but this is beingprospectively evaluated.

The clinical implications of achieving pathologic response inCLM

In patients with mCRC, pathologic response to preoperativetherapy is associatedwith better survival, which enables pathologicresponse to be used to provide an immediate prognosis afterresection of CLM. In a key study highlighting this [31], a majorpathologic response was reported in 14 of 38 patients (37%)following treatment with oxaliplatin-based chemotherapy witha significant association between improved 3-year DFS and major

Figure 2. Pathologic response classification methods: (a) tumor regression grade (TRG) scoring system (black area: tumor cells, grey area: necrotic area; fibrils; fibrosis) [31] (b)representative photomicrographs of metastases demonstrating complete, major and minor pathologic response [32]. (a) Rubbia-Brandt L et al. Importance of histological tumourresponse assessment in predicting the outcome in patients with colorectal liver metastases treated with neoadjuvant chemotherapy followed by liver surgery. Ann Oncol 2007;18(2):299e304; by permission of Oxford University Press. (b) Reprinted with permission. ! 2008 American Society of Clinical Oncology. All rights reserved. Blazer, DG III et al.: J ClinOncol 26(33), 2008:5344e51.

T. Gruenberger et al. / Surgical Oncology 21 (2012) 309e315 311

pathologic response (p ¼ 0.0014), compared with minor or nopathologic response among patients (n ¼ 106) treated with 5-fluorouracil (5-FU) alone or oxaliplatin-/irinotecan-based chemo-therapy. In addition, a major (p ¼ 0.0003) or partial (p ¼ 0.0019)pathologic response was associated with an improved 5-year OScompared with no pathologic response (Fig. 3a).

Furthermore, in a retrospective analysis, pathologic responserate was an independent predictor of survival in mCRC patients(n ¼ 305) who received preoperative irinotecan- or oxaliplatin-based chemotherapy (with or without bevacizumab) followedby resection of liver metastases [32]. Cumulative 5-year OS rateswere 75% for a complete pathologic response, 56% for a majorpathologic response, and 33% for a minor pathologic response(complete vs major response, p ¼ 0.037; major vs minorresponse, p ¼ 0.028) (Fig. 3b). However, it remains unclearwhether an increase in pathologic response as a result oftreatment intensification may also translate into an improve-ment in patient prognosis.

Pathologic response data for bevacizumab in combinationwith chemotherapy in CLM

The promising pathologic response rates reported with preop-erative chemotherapy in patients with CLM prompted the questionas to whether adding a biologic agent would further increasepathologic response rate, without necessarily increasing radio-graphic response rate, following hepatic resection. Table 1summarizes the results of a number of retrospective analysesassessing pathologic response to bevacizumab plus chemotherapyas preoperative treatment for mCRC [32,35e37].

In a non-randomized, observational study of 219 patients whounderwent hepatic resection following preoperative chemo-therapy, the frequency of ‘complete or major’ pathologic responsewas significantly higher among patients who received FOLFOX(oxaliplatineinfused 5-FUeleucovorin) with bevacizumabcompared with those who received FOLFOX alone (70% vs 45%,respectively, p < 0.001) [35], and this occurred irrespective of thenumber of treatment cycles administered (1e8 or "9 cycles).Among patients given 1e8 treatment cycles the pathologicresponse rate was 68% for FOLFOX plus bevacizumab comparedwith 47% for FOLFOX alone (p ¼ 0.007); treatment with "9 cyclesresulted in response rates of 75% and 42%, respectively (p ¼ 0.011).Clinically significant chemotherapy-specific hepatic injuries areincreasingly being reported among CLM patients receiving preop-erative chemotherapy. For example, oxaliplatin-based chemo-therapy has been associated with an increased risk of sinusoidalinjury and subsequent post-operative morbidity [38,39]. In thestudy by Kishi et al. [35], an additional beneficial finding was thatthe combination of bevacizumab with FOLFOX was associated witha significantly lower incidence of sinusoidal injury compared withFOLFOX alone both after short- and long-term treatment (1e8cycles: 5% vs 46%, respectively; p < 0.001; "9 cycles: 17% vs 58%,respectively; p ¼ 0.002). A significant decrease in oxaliplatin-related nodular regenerative hyperplasia was also seen with thecombination of bevacizumab and oxaliplatin versus oxaliplatinalone in 274 patients with surgically resected CLM (p < 0.001) [40].

In a second retrospective analysis, bevacizumab plus 5-FU andoxaliplatin (5-FU/OX) significantly reduced tumor viabilitycompared with 5-FU/OX alone (32.9% vs 45.3%, respectively;p ¼ 0.02) in 105 patients treated with preoperative chemotherapy

0 12 24 36 48 60

1.0

0.8

0.6

0.4

0.2

Time (months)

Overall survival (probability)

MjHRPHRNHR

Log rank p < 0.005

0 2 4 6 8 10

0.8

0.6

0.4

0.2

Time (years)

Overall survival (probability)

Complete vs major response p = 0.037

Major vs minor response p = 0.028

Complete responseMajor responseMinor response

1.0

a

b

Figure 3. a. Overall survival of 106 patients with complete clinical follow-up andmajor, partial, or no histologic tumor response in CLM treated with neoadjuvantchemotherapy and surgery [31]. b. Overall survival by the degree of pathologicresponse to neoadjuvant chemotherapy with or without bevacizumab [32]. (a) Rubbia-Brandt L et al. Importance of histological tumour response assessment in predicting theoutcome in patients with colorectal liver metastases treated with neoadjuvantchemotherapy followed by liver surgery. Ann Oncol 2007; 18(2):299e304; bypermission of Oxford University Press. MjHR Major histologic tumor response; PHRpartial histologic tumor response; NHR no histologic tumor response. Major(p ¼ 0.0003) and partial (p ¼ 0.0019) pathologic response following chemotherapysignificantly improved 5-year OS. (b) Reprinted with permission. ! 2008 AmericanSociety of Clinical Oncology. All rights reserved. Blazer, DG III et al.: J Clin Oncol 26(33),2008:5344e51.

Table 1Overview of published pathologic response data with bevacizumab.

Pathologic response, n (%)

Complete Major Complete þ major

Blazer et al. 2008a [32]5-FU þ oxaliplatin (n ¼ 81) 6 (12) 16 (32) 22 (44)5-FU þ oxaliplatin þbevacizumab (n ¼ 50)

7 (9) 44 (54)p < 0.001

51 (63)

Kishi et al. 2010a [35]FOLFOX (n ¼ 117) 8 (7) 45 (38) 53 (45)FOLFOX þ bevacizumab(n ¼ 102)

10 (10) 61 (60) 71 (70)p < 0.001

Ribero et al. 2007b [36]5-FU þ oxaliplatin (n ¼ 43) 5 (12) e 10 (23)5-FU þ oxaliplatin þbevacizumab (n ¼ 62)

7 (11) e 28 (45)p ¼ 0.02

Klinger et al. 2010c [37]FOLFOX (n ¼ 50) e 5 (10) e

FOLFOX þ bevacizumab(n ¼ 50)

e 19 (38)p < 0.001

e

a Complete response ¼ no residual cells; major response ¼ 1e49% residual cells.b Complete response ¼ no residual viable cells; complete þ major

response ¼ < 25% residual viable cells.c Major response ¼ TRG1 þ TRG2.

T. Gruenberger et al. / Surgical Oncology 21 (2012) 309e315312

Major/completepathologicalresponseispredictiveofbettersurvivaloutcomeinpatientreceiving

preoperativeCTfollowedbyliversurgery

Gruenberger et al, Surg Oncol 2012

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Thegoalfortheteam!

No viable tumor cellvisible !

Page 15: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Resectable

BorderlineResectable

Unresectable

10-15%

70%

Roleofmedicaloncology:optimizethequalityofresponse

PREOPERATIVE TRIPLETS(followed by post-operative3 months doublets)

-Short-term duration (£6 months)-High response rate (60-70%)

SYSTEMIC DOUBLETS

-Long-term duration (≥6 months) -Response rate 40-50%- Optimal tolerance

10-15%

Page 16: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

SelectionoftargetedagentaccordingtoK-Ras status

1st linetriplet

FOLFOX/FOLFIRI+

Targeted agent VEGF inhibitor(Avastin®

Bevacizumab)

EGFR Inhibitor(Erbitux®

cetuximab)

KRas Wild Type(no mutation)

KRas mutated

Page 17: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Downstagetumorlesionstoallowresection

and…Improvesurvival

Surgery

PreoperativeChemotherapy

(triplets)3months(<6months)

PostoperativeChemotherapy

(FOLFOX)3months

• Progressionatfirstevaluationisassociatedwithdiseaseaggressiveness,pooroutcome

• Thevalueandsafetyofresectionbecomesquestionable(delayfurtherchemo)

• FOLFOXistheonlychemotherapyvalidatedinadjuvantsetting

• Irinotecanandtargetedtherapieshaveneverbeenvalidatedinthissetting

Page 18: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

12CyclesFolfiri+cetuximab

BorderlinemetastasesMajortumorresponse

Page 19: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

factors.15,16 The potential of cure for patients with liver metastases,especially when initially unresectable, is however still questioned, ow-ing to the fact that it represents widespread, advanced systemic disease.

To date, cure has only been evaluated in patients treated withsurgery alone.17 Furthermore, although long-term disease-free sur-vival is the most appropriate definition of cure, it is usually defined aslong-term overall survival only. In this study, we evaluated the possi-bility of cure by taking into account disease-free survival and a multi-disciplinary treatment strategy combining surgery and chemotherapyin patients with initially unresectable CLM. The additional objectivewas to determine predictive factors of disease cure.

PATIENTS AND METHODS

Cohort DescriptionAll patients with unresectable CLM at the time of diagnosis who under-

went rescue surgery after downsizing chemotherapy and had a minimumfollow-up of 5 years from surgery were included. Patients considered to havetechnically unresectable disease had a too small remnant liver volume inrelation to the extent of the resection that was needed for complete resec-tion of all metastases. This was defined by the need of a resection leavingless than 30% of liver remnant, or less than 40% when patients receivedintensive preoperative chemotherapy.18

Preoperative ManagementResponse to chemotherapy was evaluated every 2 months by a multidis-

ciplinary team that included surgeons, oncologists, and radiologists by com-puted tomography (CT) according to the WHO guidelines during the initialstudy period and to the Response Evaluation Criteria in Solid Tumors duringthe final period.19,20 Patients responding to chemotherapy were reconsideredfor surgery when the overall strategy could achieve complete clearance of intra-and extrahepatic metastases. Preoperative work-up included CT of the chest,abdomen, and pelvis to evaluate liver and extrahepatic disease, as well ascolonoscopy to assess local recurrence of the primary tumor.

Hepatic ResectionResection of all detectable lesions with tumor-free margins was the ob-

jective of surgery in all patients. However, when tumor-free margins were notpossible owing to major vascular or biliary contact, resection was still indicatedprovided that all tumors could be macroscopically resected.

When downsizing by chemotherapy was not sufficient to allow a curativetreatment, surgery might include three specific techniques aimed at increasingresectability. First, PVE was performed 4 to 6 weeks before surgery in cases oftoo small estimated remnant liver volume after the planned hepatectomy.21

Second, for bilateral metastases, hemihepatectomy could be combined withthe use of radiofrequency ablation or cryotherapy for few contralateral, unre-sectable, deeply located lesions ! 3 cm in diameter. Third, when multinodularbilobar metastases could neither be completely resected by a single proce-dure22 nor treated with hepatectomy combined with ablation, two-stage hep-atectomy was considered. Postoperative complications within 2 months afterhepatectomy were recorded and classified according to the classification byClavien.23 Liver insufficiency was defined as an increase in serum bilirubinlevel to more than 50 "mol/L and a decrease in prothrombin time to lessthan 50%.24

The presence of resectable extrahepatic metastases was not a contraindi-cation to liver resection. When located in the abdomen, resection of extrahe-patic disease was performed at the same time as the hepatectomy. Forextrahepatic disease outside the abdomen, resection was generally delayed for2 to 3 months, with chemotherapy treatment during the time interval toprevent disease progression.

Postoperative ManagementFollow-up after hepatectomy included physical examination, serum tu-

mor markers (carcinoembryonic antigen and CA-19.9), and abdominal ultra-

sound 1 month after surgery and then every 4 months. CT imaging of chest,abdomen, and pelvis was performed every 8 months. As a routine policy,chemotherapy was recommended postoperatively for six to eight cycles todecrease the risk of disease recurrence.

Definition of Cured and Noncured PatientsCure was defined as a disease-free interval of 5 years or more after the last

hepatectomy or last resection of extrahepatic metastases. Furthermore, pa-tients had to be free of disease at last follow-up. Patients who died of notcuratively resected metastases or disease recurrence were defined “noncured.”

Statistical AnalysisCured patients were compared with noncured patients using the #2 test

for categoric data and the independent samples t test for continuous data. Amultivariate risk model of factors likely to predict cure and expressing a Pvalue ! .10 at univariate analysis was used to define independent predictors ofcure. P values ! .05 were considered significant. SPSS software version 13.0was used for all statistical calculations (SPSS Inc, Chicago, IL).

RESULTS

Between April 1988 and July 2002, 184 consecutive patients withinitially unresectable CLM underwent hepatic resection at our institu-tion after tumor downsizing by systemic chemotherapy. This groupconsisted of 102 men (55%) and 82 women (45%) with a median ageof 58.3 years (range, 30.8 to 79.2 years). Patients had a median numberof five metastases (range, one to 22 metastases) with a median size of50 mm at diagnosis (range, 6 to 160 mm). Metastases were bilobar in76% of cases.

Reasons for unresectability were multinodular disease (50%),large size of metastases (21%), vascular ill-location of metastases(18%), or extensive concomitant extrahepatic disease (12%). Metas-tases became resectable after a median number of one line (range, oneto four lines) and 10 cycles (range, two to 43 cycles) of chemotherapy.The last preoperative regimen consisted most often of fluorouraciland leucovorin alone (18%) or combined with oxaliplatin (62%),irinotecan (6%), or both (9%). Other regimens were administered inthe remaining 5% of patients.

0

No. of patients at risk Overall survival 161 78 41 25 18 14Disease-free survival 96 45 31 22 17 12

Surv

ival

Pro

babi

lity

Time (years)

1.0

0.8

0.6

0.4

0.2

1 2 3 4 5 6 7 8 9 10

Overall survival (n = 184)Disease-free survival (n = 184)

33%

19%

27%

15%

Fig 1. Overall and disease-free survival curves of patients with initially unre-sectable disease who underwent resection after downsizing chemotherapy.

Adam et al

1830 © 2009 by American Society of Clinical Oncology JOURNAL OF CLINICAL ONCOLOGY

Information downloaded from jco.ascopubs.org and provided by at CDMP - APHP on February 23, 2013 from 193.54.110.33Copyright © 2009 American Society of Clinical Oncology. All rights reserved.

Adam, J Clin Oncol 2009

This multidisciplinary strategy benefits to patients in terms of overall survival (curability)

Page 20: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

ImprovesurvivalAvoidunnecessarytoxicities

SystemicChemotherapy(5FU-baseddoublets)≥6months

Page 21: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Managementof1st linetherapyaccordingtoevaluation@3months

1st lineDoublets

(FOLFOX orFOLFIRI) Switchto

otherdoublet(Discusstargeted

therapy)

Maintain sameregimen

for 3 months

Objective Responseor Stable Disease

(70-75%)

ProgressiveDisease (25-30%)

Page 22: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Improvement of liver-disease control(disease mainly/exclusively limited to the liver)

Potentialindicationsforliver-directedtherapies

- Acquired resistance after systemic chemotherapy (after 1-1.5 year of controlled disease)

- Major preoperative dowstaging for borderline lesions in combination to systemic therapy

- Adjuvant treatment after resection of multiple lesions with limited response to previous systemic chemotherapy

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Conclusions

• Resectable:PerioperativeFOLFOXismainstay(3+3,noprovedaddedvalueofoptimizingresponse)

• Borderline:Preoperativetriplets(withatargetedagent)optimizesthequalityofresponsebeforesurgery(thenadjuvantFOLFOX)

• Neverresectable:Longtermdiseasecontroliskeyandlivertargetedtherapyshouldbediscussed

Page 27: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

LePéritoineNouveauxtraitementsoncologiquesdescancerscolorectaux

Page 28: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

DoweknowthespontaneoussurvivalofpatientswithisolatedPC?

Notwellreportedintheliterature

<6monthsforCRC<4monthsforgastriccancer

<3monthsforpancreaticcancer

EVOCAPEstudy(370patientswithPCofGIorigin,only26%treatedwithCTü MedianOS:5.2,3.1,and1.5monthsforCRC,gastric,andpancreasrespectivelyü Impactoftumorburden:OSrangingfrom9.8months(smallstageIgranulations

<5mm)to3.7months(largestade IVmasses>2cm)

Sadeghi etal,Cancer2000

Page 29: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

Peritonealcarcinomatosis (PC)isonewayofdisseminationamongothersformalignancies

- 65-90%ofcolorectalcancers,60%ofgastriccancers- Distantvisceralmetastasisrequiresystemicchemotherapytoensureglobaldiseasecontrol

- PCisarisingproblemsincesystemicchemotherapyhasimprovedpatients’survival>6months

Visceralmetastasisarethemorefrequentsiteofdisseminationforrecurrentmalignancies

Page 30: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

PIPAC

Page 31: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

L’immunothérapieNouveauxtraitementsoncologiquesdescancerscolorectaux

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Page 33: Place des nouveaux traitements dans les cancers colorectaux. Eric Raymond Enseignement Post Universitaire à Saint-Joseph le 27 avril 2017

MHC

PD-L1

PD-1

PD-1

T-cellreceptor

PD-L2

Tcell

NFκB

Other

PI3K

Tumorcell

IFNγ

IFNγR

Shp-2

Antibodies

ImmuneCheckpointantibodies

1. Topalian SL,etal.NEnglJMed.2012;366:2443-2454

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Conclusion

• Letraitementdesmétastaseshépatiquesdescancerscolorectauxrequièrel’accèsàunplateaudesoinspluridisciplinairepouraugmenterleschancesdeguérison

• Denouvellesapprochesmédico-chirurgicalessontencoursd’évaluationpourletraitementdelacarcinosepéritonéale

• L’immunothérapieestuneapprocheprometteusedontlaplaceestencoursd’évaluationdanslescancerscolorectauxavancésoumétastatiques