Abstract 422P
Background
Rectal cancer incidence in early onset (EO) patients (pts) is increasing; defining optimal treatment (Tx) is crucial. We previously performed an IPD meta-analysis of 3 RTs testing the addition of oxaliplatin (OX) to standard fluoropyrimidine-based CRT in LARC; we identified a signal for disease-free survival benefit in pts <60y (Fontana, ASCO2020). Here, we focus on pathological complete response (ypCR) in different age cohorts.
Methods
RTs included CAO/ARO/AIO-04, ACCORD-12, PETACC-6. Primary endpoint: ypCR. Analyses by intention to treat (ITT) stratified by trial. Age cut-offs: 60y/50y. Multivariate analyses (MVA) to evaluate confounders were performed including age (continuous/categorical), Tx, trial, sex, stage at diagnosis (I-II versus ≥III).
Results
2914 pts included: median age 63 (24-88); 350 (12%) were <50y (EO); 1166 (40%) were <60y; 70% male; 79% had a performance status (PS) =0; 72% had stage ≥III Younger pts (<60y) had better PS (PS0: 86% vs 75%; p<0.001), higher stage at diagnosis (≥III 75% vs 70%, p:0.009) with no difference in sex, Tx and trial distribution In ITT ypCR significantly increased from 13% (control - C) to 16% (OX) (Odds Ratio [OR] 1.28, 95%CI 1.04-1.57, p=0.024 stratified by trial). In pts >60 there was a significant increase in ypCR with OX (C 12% vs OX 17%; OR 1.47, 95%CI 1.12-1.93; p=0.01); no increase was seen in pts<60 (p=0.89) or in pts<50 (p=0.72). Interaction on ypCR between Tx and age was not significant (60 cut-off p=0.11, 50 cut-off p=0.74). In MVA, no variables associated with ypCR were identified with age as continuous variable (table) or with 60/50 age cut-offs. Table: 422P
| p-value | ||
| Tx | OX vs C | 0.43 |
| Age | continuous | 0.15 |
| Sex | Female vs Male | 0.15 |
| Stage | ≥III vs I-II | 0.49 |
| Interaction | Age*Tx | 0.24 |
Conclusions
In this IPD meta-analysis younger pts had better PS but more advanced tumour at diagnosis. Adding OX to CRT significantly increase ypCR but no interaction between Tx and age/explored variables was shown. Effort to increase sample size of EO pts is on-going.
Clinical trial identification
NCT00766155, NCT00349076 and NCT00227747.
Editorial acknowledgement
Legal entity responsible for the study
Adolescent and Young Adult Gastrointestinal Cancer Task Force – EORTC.
Funding
Has not received any funding.
Disclosure
E. Fontana: Advisory/Consultancy, Spouse/Financial dependant: Astellas Pharma; Bristol-Myers Squibb; Celgene; Servier; Travel/Accommodation/Expenses, Licensing/Royalties: Patent No: 1716712.3 pending; Travel/Accommodation/Expenses, Spouse/Financial dependant: Bristol-Myers Squibb; Servier. E.C. Smyth: Advisory/Consultancy: Astellas Pharma; Bristol-Myers Squibb; Celgene; Servier; Licensing/Royalties: Patent No: 1716712.3 pending; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Servier. C. Rödel: Research grant/Funding (institution): German Cancer Aid; German Cancer Aid. R.D. Hofheinz: Honoraria (institution): Amgen; BMS; Lilly; Medac; Merck Serono; MSD; Roche; Sanofi; Advisory/Consultancy: Amgen; BMS; Merck Serono; MSD; Roche; Sanofi; Speaker Bureau/Expert testimony: Amgen; BMS; Lilly; Merck; MSD; Roche; Sanofi; Servier; Research grant/Funding (institution): Deutsche Kresbhilfe; Medac; Sanofi. D. Arnold: Honoraria (institution): Bayer; Bristol-Myers Squibb; Merck Serono; Roche/Genentech; Servier; Terumo; Advisory/Consultancy: Bayer; Biocompatibles; Bristol-Myers Squibb; Merck Serono; MSD Oncology; Servier; Terumo; Research grant/Funding (institution): Roche/Genentech; Sanofi; Travel/Accommodation/Expenses: Bayer; Merck Serono; Roche/Genentech. H.J.E-V. Schmoll: Honoraria (institution): Amgen; Roche; Advisory/Consultancy: Bayer; Bristol-Myers Squibb; Roche; Research grant/Funding (institution): Amgen; Roche; Travel/Accommodation/Expenses: Amgen; Bayer; Roche. E. Van Cutsem: Advisory/Consultancy: Array; AstraZeneca; Bayer; Bristol-Myers Squibb; Celgene; Halozyme; Lilly; Merck KGaA; Merck Sharp & Dohme; Novartis; Roche; Servier; Research grant/Funding (institution): amgen; Bayer; Boehringer Ingelheim; Bristol-Myers Squibb; Celgene; Ipsen; Lilly; Merck; Merck KGaA; Novartis; Roche; Servier. K.M. Haustermans: Honoraria (institution), Research grant/Funding (institution): Varian Medical Systems. A. Stein: Advisory/Consultancy: Amgen; Bristol-Myers Squibb; Merck KGaA; MSD; Roche; Speaker Bureau/Expert testimony: Amgen; Bayer; Bristol-Myers Squibb; Celgene; Lilly; Merck KGaA; Roche; Sanofi; Servier; Research grant/Funding (institution): Bristol-Myers Squibb; Merck KGaA; Roche; Sanofi; SERVIER; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Merck KGaA; Roche. M. Moehler: Honoraria (institution): Amgen; AstraZeneca/MedImmune; Bristol-Myers Squibb; Lilly/ImClone; Merck Serono; MSD Oncology; Roche/Genentech; Servier; Taiho Pharmaceutical; Advisory/Consultancy: Amgen; Bayer; Lilly; Merck Serono; MSD; Nordic Group; Pfizer; Roche; SERVIER; Taiho Pharmaceutical; Yakult; Research grant/Funding (institution): Amgen; AstraZeneca; Jennerex; Leap Therapeutics; Merck Serono; MSD; Travel/Accommodation/Expenses: Amgen; ASCO; Bayer; ESMO; German Cancer Society; Merck Serono; MSD; Roche. F. Lordick: Honoraria (institution): AstraZeneca; BioNTech AG; Bristol-Myers Squibb; Elsevier; Infomedica; Lilly; Medscape; Merck KGaA; Merck Sharp & Dohme; Roche; Servier; Advisory/Consultancy: Amgen; Astellas Pharma; Beigene; Bristol-Myers Squibb; Lilly; Merck Sharp & Dohme; Servier; Zymeworks; Research grant/Funding (institution): Bristol-Myers Squibb; Travel/Accommodation/Expenses: Bristol-Myers Squibb; Lilly. M. Di Maio: Honoraria (institution): AstraZeneca; Bristol Myers Squibb; Eisai; Janssen; Mediolanum Farmaceutici; Merck Sharp & Dohme; Pfizer; Takeda; Advisory/Consultancy: AstraZeneca; Eisai; Janssen; Mediolanum Farmaceutici; Merck Sharp & Dohme; Pfizer; Takeda; Research grant/Funding (institution): Tesaro. All other authors have declared no conflicts of interest.