All times are listed in CEST (Central European Summer Time)
- Andrea Cercek (New York, United States of America)
- Marco Gerlinger (London, United Kingdom)
LBA21 - FOLFOX/FOLFIRI plus either bevacizumab or panitumumab in patients with initially unresectable colorectal liver metastases (CRLM) and left-sided and RAS/BRAFV600E wild-type tumour: Phase III CAIRO5 study of the Dutch Colorectal Cancer Group
- Marinde J. Bond (Utrecht, Netherlands)
Abstract
Background
Patients (pts) with initially unresectable CRLM may qualify for curative-intent local therapy after downsizing by induction systemic therapy. CAIRO5 was designed to find the optimal induction regimen. We present results of pts with left-sided and
Methods
Pts were randomised between FOLFOX/FOLFIRI (patient preference) plus either bevacizumab (arm A) or panitumumab (arm B) up to 12 cycles. Prior systemic or local therapy for metastases was not allowed. (Un)resectability of CRLM was assessed by a liver expert panel of surgeons and radiologists, at baseline by predefined criteria and every 2 months thereafter by individual opinion. Primary endpoint was progression-free survival (PFS). Pts were stratified by potentially resectable vs permanently unresectable CRLM, serum LDH (normal/abnormal) and choice of irinotecan vs oxaliplatin. 256 events were required to detect a hazard ratio (HR) of 0.70 for PFS with 80% power and 2-sided log-rank test at 5% assuming a median PFS of 11.6 months in arm A.
Results
236 pts (118 in each arm) were included in 43 Dutch sites from November 2014 until closure due to futility in March 2022. 6 ineligible pts were excluded. Median follow up was 44 months. Main characteristics were (arm A/B): median age 59/60, male 61/63%, synchronous CRLM 88/92%, prior adjuvant chemotherapy 4/3%, median number of CRLM 12/12. With 197 events, median PFS in arm A vs B was 10.6 vs 10.3 months (stratified HR 1.12, 95% CI 0.84-1.50, p=0.44). Response rate (RR) was 52% vs 76% (p<0.01). Median depth of response (DOR) was 33% vs 49% (p<0.01). R0/1 resection ± ablation rate was 58% vs 56% (p=0.79). Grade ≥3 toxicity occurred in 52% vs 69% (p=0.01), Clavien Dindo grade ≥3 surgical complications in 21% vs 14% (p=0.30).
Conclusions
In first-line treatment of pts with initially unresectable CRLM and left-sided and
Clinical trial identification
NCT02162563; EudraCT, 2013-005435-24.
Legal entity responsible for the study
Dutch Colorectal Cancer Group.
Funding
This study was supported by unrestricted grants from Roche and Amgen. The funders had no role in the design, conduct and submission of the study, nor the decision to submit the abstract for publication.
Disclosure
J.W.B. de Groot: Financial Interests, Institutional, Advisory Role: Servier, Pierre Fabre and BMS. M.P. Hendriks: Financial Interests, Institutional, Funding: Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Eisai, Ipsen, Merck Sharp & Dohme, Novartis, Pfizer and Roche. K.P. de Jong: Financial Interests, Institutional, Funding: Philips. C.J.A. Punt: Financial Interests, Institutional, Advisory Role: Nordic Pharma. All other authors have declared no conflicts of interest.
LBA22 - Phase III study with FOLFIRI/cetuximab versus FOLFIRI/cetuximab followed by cetuximab (Cet) alone in first-line therapy of RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC) patients: The ERMES study
- Armando Orlandi (Rome, Italy)
Abstract
Background
The optimal intensity of anti-EGFR-based first line therapy for
Methods
Patients with untreated
Results
From May 2015 to March 2020, 606 pts were randomized: 300 assigned to arm A and 306 to arm B. Median FU was 22.3 (15-33.8) months (m). Drop-out rate was around 40%. In the mPP population (arm B 183/arm A 154) 291 events occurred with mPFS of 10
Conclusions
The ERMES study does not demonstrate non-inferiority of maintenance with Cet alone. The higher-than-expected drop-out rate and subsequent reduced statistical power might have impaired the results. The ITT analysis and OS results are suggestive for a strategy of de-escalation treatment with only cetuximab. Ongoing translational analyses might allow to select pts benefitting from de-escalation strategy.
Clinical trial identification
NCT02484833.
Legal entity responsible for the study
Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome.
Funding
Merck Serono S.p.A., Rome, Italy, an affiliate of Merck KGaA (CrossRef Funder ID: 10.13039/100009945).
Disclosure
C. Pinto: Non-Financial Interests, Personal, Funding: Lilly; Financial Interests, Personal, Funding: Bayer, BMS, Ipsen, AstraZeneca, Merck. A. Orlandi: Financial Interests, Personal and Institutional, Funding: MERCK; Financial Interests, Personal, Invited Speaker: Novartis, Lilly, Amgen; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Advisory Board: Daiichi Sankio. L. Antonuzzo: Financial Interests, Personal, Advisory Board: Merck. All other authors have declared no conflicts of interest.
Invited Discussant LBA21 and LBA22
- Julien Taieb (Paris, France)
Q&A
- All Speakers (Lugano, Switzerland)
314O - Adjuvant hyperthermic intraperitoneal chemotherapy in locally advanced colon cancer (HIPECT4): A randomized phase III study
- Alvaro Arjona-Sanchez (Cordoba, Spain)
Abstract
Background
Peritoneal metastasis in locally advanced colon cancer (T4 stage) is estimated around 25% at 3 years from surgical resection with a poor prognosis. There is controversy about the results using prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in this group of patients. We led a randomized controlled trial to determine the efficacy and safety of adjuvant HIPEC in patients with locally advanced colon cancer.
Methods
We did an open-label, randomized phase III study in 17 hospitals in Spain. Eligible patients were aged 18-75 years and had locally advanced primary colorectal cancer diagnosed preoperatively (cT4NxM0). Patients were randomly assigned (1:1) to surgery or surgery plus HIPEC (mitomycin C 30 mg/m2 during 60 minutes), both followed by systemic adjuvant chemotherapy. Randomisation was done via a web-based system, with stratification by treatment centre and gender. The primary outcome was 3 years loco-regional control rate, defined as the time from treatment to peritoneal disease recurrence or death form any cause, analysed by intention to treat (ITT). DFS and OS were secondary endpoints.
Results
Between November 2015 and January 2021 184 patients were recruited and randomized (89 experimental vs. 95 control). The median of follow-up was 36 (IQR 27-36) months. Demographic, tumour features, surgical management and final pathology reports were similar between both groups. The loco-regional control (LC) was improved in the experimental arm (35,3 ± 0.4 vs. 33.2 ± 0.8 months) with a 3 years LC rate of 97% vs. 87% (p = 0.025). No differences were observed in DFS and OS. The pT4 subgroup showed a clear benefit of LC in the HIPEC arm. No differences in morbidity were observed between groups.
Conclusions
The addition of hyperthermic intraperitoneal chemotherapy with mitomycin C to a complete surgical resection for locally advanced colon cancer improves the loco-regional control rate. This benefit becomes more evident in the subgroup of patients with pT4 colon cancer.
Clinical trial identification
NCT02614534.
Legal entity responsible for the study
IMIBIC Maimonides Biomedical research Institute cordoba, Spain. Universitary Hospital Reina Sofia, Cordoba, Spain.
Funding
FIBICO (Biomedical Research Foundation, Cordoba) and Spanish Surgeon's Association (AEC).
Disclosure
All authors have declared no conflicts of interest.
LBA23 - Avelumab versus standard second-line treatment chemotherapy in metastatic colorectal cancer (mCRC) patients with microsatellite instability (MSI): The SAMCO-PRODIGE 54 randomised phase II trial
- Julien Taieb (Paris, France)
Abstract
Background
Immune checkpoint inhibitors have failed in treating mCRC patients (pts) except those with MSI/dMMR tumours. However, in pts with MSI/dMMR mCRC, only one randomized trial in the first-line setting, showed the superiority of an anti-programmed death 1 (anti–PD-1) antibody over standard treatment. The SAMCO-PRODIGE 54 trial aimed to evaluate efficacy and safety of an anti-programmed death ligand-1 (anti–PD-L1) antibody compared with a standard treatment in the second-line setting in pts with MSI/dMMR mCRC.
Methods
In this national, multi-center, open-label phase 2 trial, pts with MSI/dMMR mCRC who progressed on oxaliplatin or irinotecan-based first-line therapy ± targeted agents, were randomized to receive standard second-line therapy or avelumab (10 mg/kg q2w). Primary endpoint was progression-free survival (PFS) according to RECIST 1.1 criteria, evaluated by investigators, in pts with confirmed MSI/dMMR status and that received at least one dose of planned treatment (modified intention-to-treat [mITT] population). Pts were stratified on WHO performance status (0-1 vs 2),
Results
From April 2018 to April 2021, in 49 French sites, 122 pts were enrolled in the mITT population for efficacy analyses (61 in arm A: control; 61 in arm B: avelumab). There were no differences in pts and tumours characteristic between the two arms.No new safety concern in either arms have been detected. After a median follow-up of 33.3 months (range, 28.3 to 34.8), avelumab was superior to chemotherapy +/- targeted agents with respect to PFS (p=0.025). 12- and 18-month PFS rates were 19% and 9% in arm A, and 31% and 27%, in arm B. Objective response rates were similar in both arms (28% vs 30%, p=0.45). Among pts with a disease control, 75% in the avelumab group, compared with 20% in the control group, had ongoing disease control at 18 months. Treatment-related adverse events ≥ grade 3 occurred in 31.7% of the pts in the avelumab group, compared with 53.1% in the control group.
Conclusions
The SAMCO-PRODIGE 54 randomized phase II study demonstrated, in second-line for dMMR/MSI mCRC pts, the safety and efficacy of avelumab.
Clinical trial identification
NCT 03186326.
Legal entity responsible for the study
FFCD.
Funding
Merck Serono.
Disclosure
J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Roche, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis, Pierre Fabre, Roche, Servier; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD). T. André: Financial Interests, Personal, Advisory Board, Advosiry Board on February 12, 2021: Astellas pharma; Financial Interests, Personal, Advisory Board, Advisory Board on February 2021: Kaleido Biosciences; Financial Interests, Personal, Invited Speaker, and advisory board: Amgen; Financial Interests, Personal, Invited Speaker, Invited speaker in a symposuim december 2020: AstraZeneca; Financial Interests, Personal, Advisory Board, and consultant fees and consultant contract: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board, Advisory board in Janaury 2020: Clovis; Financial Interests, Personal, Advisory Board, Advisory board in january 2020: Gritstone Oncology; Financial Interests, Personal, Advisory Board: Haliodx; Financial Interests, Personal, Advisory Board, and consultant fees/consultant contract and invited speaker: MSD Oncology; Financial Interests, Personal, Invited Speaker, and other: Pierre Fabre; Financial Interests, Personal, Invited Speaker, in an symposium in 2020: Roche; Financial Interests, Personal, Invited Speaker, in a meeting in 2019: Ventana; Financial Interests, Personal, Invited Speaker, In a educational meeting in 2019: Sanofi; Financial Interests, Personal, Advisory Board, in a symposium in 2020: Servier; Financial Interests, Personal, Expert Testimony, Consultant with personnal fees and invited speaker: Servier; Financial Interests, Personal, Advisory Board, in 2019: GSK; Financial Interests, Personal, Invited Speaker, in 2020 and 2021: GSK; Financial Interests, Personal, Expert Testimony, consultant contract: Seagen; Financial Interests, Personal, Invited Speaker, Virtual symposium Lecture: 1 MSI-H CRC: Implementation of Immunotherapy in clinical practice (30 minutes) – (this will be pre-recorded)Q&A – Live Q&A – (10 minutes) (on July 2, 2021): MSD Oncology; Financial Interests, Personal, Invited Speaker, June 2022: Sanofi; Financial Interests, Personal, Expert Testimony, Contract: Merck & Co., Inc, Gritstone Oncologie; Financial Interests, Personal, Advisory Board, Contrat: BMS; Financial Interests, Institutional, Other, Investigator and scientific comitee president: Gercor Academic group; Financial Interests, Institutional, Invited Speaker, PI Garnet study: GSK; Financial Interests, Institutional, Invited Speaker, Keynote 164 and 171 and 811: MSD; Financial Interests, Institutional, Invited Speaker, BMS CA209-8HW, BMS CA209-142, BMS CA209-577: BMS; Financial Interests, Institutional, Invited Speaker, SPOTLIGHT study: Astellas; Financial Interests, Personal, Invited Speaker, and internationnal PI: Servier; Non-Financial Interests, Invited Speaker, Vice President: Gercor group; Non-Financial Interests, Invited Speaker, Member of scientific committee: ARCADFoundation. All other authors have declared no conflicts of interest.
Invited Discussant 314O and LBA23
- Andrea Cercek (New York, United States of America)
Q&A
- All Speakers (Lugano, Switzerland)