HIGHLIGHTS DANS LE CANCER DU RECTUM
REGINA TRIAL
Dr Yeter Gökburun
Gastro-Entérologie et Oncologie Digestive
Centre Hospitalier Régional de Namur
Institut Jules Bordet
REUNION MEDICALE 29-04-2021
2e cancer le plus fréquent chez la femme après celui du sein
3e cancer le plus fréquent chez l’homme après ceux de la prostate et du poumon
CAUSES ET FACTEURS DE RISQUE
Age: > 50 ans dans 90% cas
Les habitudes de vie en cause :
alimentation riche, notamment en graisses animales; viande rouge;
Inactivité physique;
Surpoids;
Alcool;
Tabac
ATCD personnels et familiaux : polypes, CCR, MICI, PAF, Syndrome de Lynch
D+ abdominale ou anale
Sang dans les selles
Alternance diarrhée et constipation
Epreintes
TR: masse palpée
Amaigrissement , anorexie et fatigue
Test iFOBT
CLINIQUE
Glynne-Jones, Ann Oncol 2017
ESMO guidelines for nonmetastatic rectal cancer (2017)
Swedish Rectal Cancer Trial, N Engl J Med 1997
1. Roh et al, J Clin Oncol 2009
2. Sauer et al, N Engl J Med 2004
Sauer et al, N Engl J Med 2004
RCT NA
RCT A
Sauer et al, J Clin Oncol 2012
Pied de page à compléterDutch CKVO 95-04 TME TrialKapiteijnet al, N EnglJ Med 2001
Cochrane Database Syst Rev 2013
Erlandssonet al, Lancet Oncol 2017
2021: Where are we?
3-yr DFS
RAPIDO
30.4% [95%CI: 26.1-34.6]
for the CRT group
23.7% [95%CI: 19.8-27.6]
for the TNT group
3-yr DRTF
Total neoadjuvant therapy: RAPIDO and PRODIGE 23
CRT Surgery
High-risk
rectal cancer*
N=885
Optional CAPOX x8
or FOLFOX x12
SCRTCAPOX x6
or FOLFOX x9Surgery
R
PRODIGE 23
CRT Surgery
Stage II-III
rectal cancer
N=461
mFOLFOX x12
or Cape x8
mFOLFIRINOX x6 CRT Surgery
R
mFOLFOX x6
or Cape x4
Bahadoer, ASCO 2020; Bahadoer, Lancet Oncol 2020; Conroy, ASCO 2020
* ≥1 high-risk features: CRM+, T4, N2, lateral N+, EMVI
Treatment pCR p value
Standard 14.3% <0.001
TNT 28.4%
Treatment pCR p value
Standard 12.1% <0.001
TNT 27.8%
Total neoadjuvant therapy: RAPIDO and PRODIGE 23
Which sequence to choose?
- Improved DFS and MFS with Polychemo
- Improved compliance with chemoradiation therapy in group with
consolidation chemo (CAO/ARO/AIO-12: 97% vs 91%)
- DFS-3yr: similar results (75.7% Prodige 23 – 76,4% Rapido)
- No significant improvement in OS
- No significant improvement in local control in both studies
- Same results for pRC
- Tren_
SCRT or CRT
The new paradigm for stage II-III rectal cancer
The “treatment ceiling effect” in rectal cancer
TME
Neoadj RT
Neoadj CRT
Neoadj SCRT
Adj CT
TNT
The “treatment ceiling effect” in rectal cancer
TME
Neoadj RT
Neoadj CRT
Neoadj SCRT
Adj CT
TNT
Immunotherapy?
- Variation anormale du nombre de
séquences répétées dans l'ADN
tumoral comparé à l'ADN du même
patient provenant de tissu sain
- Décrite d’abord dans le syndrome de
Lynch ou syndrome HNPCC
(hereditary nonpolyposis colon
cancer) (95 % des cas)
- 15 % CCR sporadiques
- Recherche par PCR de 5 marqueurs
microsatellites répartis dans le
génome des cellules tumorales.
INSTABILITE DES MICROSATELLITES (MSI)
Why immunotherapy for rectal cancer?
Walle, Ther Adv Med Oncol 2018; Vanpouille-Box, Nat Comm 2017
The vast majority of rectal cancers are MSS/MMRp, but…
The immunomodulatory effects of RT may increase the therapeutic potential of ICIs
Immunotherapy for rectal cancer is now a hot topic
About 30 ongoing/planned
clinical trials (ie, >1700 pts)
with ICIs or other immuno-
modulatory agents
REGorafenib and nIvolumab iN rectAl cancer
(REGINA)
A phase II trial of neoadjuvant regorafenib in combination
with nivolumab and short-course radiotherapy in
intermediate-risk, stage II-III rectal cancer
The REGONIVO (EPOC1603) trial
Gastr(n=25)
Colon(n=25)
≥3 prior linesof tx
64% 80%
Prior ICIs 28% 0
MMRp/MSS 100% 96%
Median TMB 9.2 10.9
CPS ≤1 58% 67%
Phase Ib trial (JAPAN)
Median PFS 5.6 m (GC) and 7.9 m (CRC)1-year PFS 22.4% (GC) and 41.8% (CRC)
Median OS 12.3 m (GC) and NR (CRC)1-year PFS 55.3% (GC) and 68% (CRC)
ORR 44% ORR 36%
Fukuoka, J Clin Oncol 2020
REGorafenib and nIvolumab iN rectAl cancer (REGINA)
Single-arm phase II study
Simon’s two-stage design
+ early safety analysis
Primary endpoint: pCR
Sample size: max 60 pts
REGINA – Main inclusion criteria
Histologically or cytologically verified adenocarcinoma of the rectum
Tumour with distal border below the peritoneal reflection and within 15 from the anal verge
Intermediate-risk rectal cancer as defined by the followingcriteria on baseline pelvic MRI:
• cT3/T4a, Nany or cT1-2, N+
• No involvement/threatening of the mesorectal fascia
• No involvement of lateral pelvic lymph nodes
Absence of distant metastases at baseline CT scan of the thorax-abdomen and (PET)/CT scan
SurgeryDr Anguraj Sadanandam
Systems and Precision Cancer Medicine Team
Prof Jeroen RaesLaboratory of Molecular Bacteriology (Rega Institute)
S
ur
g
er
y
Prof Eleonora LeucciTrace Platform
Prof Diether Lambrecths VIB-KU Leuven Center for Cancer Biology
Dr Francesco SclafaniGUTS Lab
Prof François GhiringhelliGenetic and Immunotherapy Medical Institute
Center Georges Francois Leclerc
REGINA – TR plan
UZ ANTWERPENUZ GENT
AZ GROENINGESAINT-LUC
ERASME
BORDET
GHd CHARLEROI
CHR NAMURCHU NAMUR - GODINNE
CHIREC - DELTA
REGINA – Participating centres
Please, considering referring your
patients to the nearest study site!
TNT is a new standard of care for high-risk stage II and stage III cancers
A substantial proportion of locally-advanced rectal cancer patients still
experience treatment failure and tumour recurrence
Any further survival gain in this setting is likely to be achieved with alternative
treatment strategies
Preclinical data provide a sound rationale for the combination of ICIs, multi-
TKI and RT
The REGINA trial is a novel-design clinical trial that: will build on data from studies of ICIs with standard (C)RT
will provide an optimal in vivo platform for correlative biomarker analyses
Conclusions
THANKS
If you have any questions: [email protected]