3O - PRODIGE 68 - UCGI 38 - SOREGATT: A randomized phase II study comparing the sequences of regorafenib (reg) and trifluridine/tipiracil (t/t) after failure of standard therapies in patients (pts) with metastatic colorectal cancer (mCRC)

Background

Once first-line treatments (trt) for mCRC have been used, or are no longer appropriate, pts are eligible for either reg or t/t. Although both trt are approved in mCRC, no randomised trial has investigated the sequence of reg and t/t. We have designed this trial to evaluate if trt sequence has an impact on the number of pts who can received both trt and on survival.

Methods

Pts with mCRC, ≥18 yo, ECOG PS 0-1, after failure of fluoropyrimidine-based chemotherapy combined with oxaliplatin and/or irinotecan plus EGFR (if RAS wild-type) and/or VEGF inhibitors were assigned in a 1:1 ratio in arm A (reg then t/t) or arm B (t/t then reg). ReDOS scheme was used. The primary endpoint is trt feasibility, assessed as the rate of pts able to receive at least 2 cycles of both trt, corresponding to the 1st tumor evaluation at each line. Secondary endpoints include duration of trt, progression-free survival in 1st sequence of trt (PFS1), time to failure of strategy (TFS), overall survival (OS) and time to deterioration of ECOG PS ≥2.

Results

A total of 234 pts out of 340 planned were randomized (arm A/B : 114/119) in 30 European centers. Study was prematurely stopped following disease management changes induced by SUNLIGHT trial results (t/t + beva). At time of data cut-off, the median follow-up was 19 mo. Main characteristics were (arm A/B): median age 68/67 yo; male 51/66%; PS0 34/35%; right, left side, rectum: 30, 46, 24% / 35, 35, 30%. The rate of pts able to receive at least 2 cycles of both trt is 40%/56% (p=0.018) with a median trt duration of 95/111 d. Main reason for end of trt were progression 82/90% and toxicity 14/8% in first phase; progression 80/78% and toxicity 12/20% in second phase. 39% of arm A pts do not switch to subsequent trt vs 27% in arm B, mainly due to deterioration of general condition or death. Median TFS is 3.2 mo [2.4 ;3.5] vs 3.7 [3.5 ; 4.0] in arm A vs B. Secondary endpoints will be presented at the congress.

Conclusions

SOREGATT trial results show that the trt feasibility, i.e. rate of pts able to receive at least 2 cycles of both trt, is better with the sequence t/t then reg. Secondary endpoints will allow to confirm if there is an impact on survival outcomes.

Clinical trial identification

EudraCT 2019-004196-39.

Legal entity responsible for the study

Unicancer.

Funding

Bayer.

Disclosure

M.P. Ducreux: Financial Interests, Personal, Invited Speaker: Roche, Amgen, Pierre Fabre, Merck KGaA, Pfizer, Bayer, Lilly, Servier, MSD, BeiGene; Financial Interests, Personal, Advisory Board: Roche, Basilea, Pierre Fabre, Boehringer Ingelheim, Rafael, Servier, Zymeworks, Ipsen, Bayer, HalioDX, Lilly, GSK, Daiichi Sankyo, MSD, Servier, BeiGene; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of bevacizumab in NET: Roche; Financial Interests, Institutional, Funding, Partial funding of a trial evaluating the role of steptozotocin in NET: Keocyt; Financial Interests, Institutional, Invited Speaker: Rafael, Amgen; Financial Interests, Institutional, Funding: Bayer; Other, My wife is head of the oncology business unit in the French Affiliate of Sandoz: Sandoz France. M. Ben Abdelghani: Financial Interests, Personal, Invited Speaker: Incyte, Servier, Pierre Fabre; Financial Interests, Personal, Advisory Board: Merck, BMS, Bayer; Financial Interests, Institutional, Advisory Board: Deciphera. D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, Amgen, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation Francophone de Cancerologie Digestive. O. Bouche: Financial Interests, Personal, Advisory Board: Amgen, Merck, Apmonia Therapeutics, Deciphera, Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, Bayer. J. Viaud: Financial Interests, Personal, Invited Speaker: MSD, Servier, Amgen, Pfizer, Sandoz. F. Khemissa Akouz: Financial Interests, Personal, Invited Speaker: Servier, AstraZeneca; Other, fees for congress (jfhod): MSD; Other, fees for congress: Servier. J. Bachet: Financial Interests, Personal, Advisory Board: AbbVie, Acobiom, Amgen, Bayer, Biomunex, BMS, GSK, LEO Pharma, Merck Serono, MSD, Pierre Fabre, Servier, Takeda, Viatris; Financial Interests, Personal, Invited Speaker: AbbVie, Acobiom, Amgen, Bayer, Biomunex, BMS, GSK, LEO Pharma, Merck Serono, MSD, Pierre Fabre, Servier, Takeda, Viatris. C. Coutzac: Financial Interests, Personal, Advisory Board: BMS, Servier, Pierre Fabre, Merck Serono; Financial Interests, Institutional, Advisory Board: BMS, Amgen; Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, AstraZeneca, MSD, ImCore Roche Genentech. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Expert Testimony: Astellas, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, Steering Committee of clinical trial: Novartis; 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); Non-Financial Interests, Other, steering committee of clinical trials: Pfizer, Servier. N. Fares: Financial Interests, Personal, Invited Speaker: Pierre Fabre, Servier, AstraZeneca; Financial Interests, Personal, Advisory Board: Roche. D. Botsen: Financial Interests, Personal, Invited Speaker: Servier, Pierre Fabre, MSD, Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono, Accord Healthcare. All other authors have declared no conflicts of interest.