Abstract 966
Background
Pt- and tumour-related characteristics may dictate goal of treatment in first-line mCRC, as suggested by updated ESMO guidelines (previewed at WCGIC 2015). Addition of epidermal growth factor receptor inhibitors to chemotherapy improves objective response rates (ORR) and may improve resection rates but their role in pts requiring disease control is less clear. This exploratory analysis from the PRIME trial assessed the efficacy of pmab + FOLFOX4 vs FOLFOX4 according to the goal of treatment (cytoreduction or disease control).
Methods
PRIME (NCT00364013) was an open-label randomised phase III trial of first-line pmab + FOLFOX4 vs FOLFOX4. Pts with RAS WT/BRAF WT mCRC were retrospectively classified using baseline characteristics to define the goal of treatment. Cytoreduction Group: liver-limited disease (LLD) and/or symptomatic; Disease Control Group: non-LLD and asymptomatic. Tumour-related symptoms were defined as an EQ-5D pain/discomfort scale score >1 at baseline or an Eastern Cooperative Oncology Group score of 1.
Results
Overall 439 pts had RAS WT/BRAF WT mCRC. Progression-free (PFS) and overall survival (OS) were longer for pmab + FOLFOX4 vs FOLFOX4 in both groups (Table). Results were similar when the ECOG = 1 definition was used (Cytoreduction Group [n = 214] PFS hazard ratio [HR]: 0.77, OS HR: 0.76; Disease Control Group [n = 197] PFS HR: 0.64, OS HR: 0.68). ORR were higher for pmab + FOLFOX4 compared with FOLFOX4 in both groups (Table).
| Median, months | |||
|---|---|---|---|
| PFS | OS | ORR | |
| Cytoreduction Group (n = 252) | |||
| Pmab + FOLFOX4 | 10.0 | 23.8 | 80/124 (64.5%) |
| FOLFOX4 | 9.3 | 20.2 | 63/122 (51.6%) |
| HR (95% CI) | 0.73 (0.56-0.96) | 0.78 (0.60-1.03) | |
| Disease Control Group (n = 172) | |||
| Pmab + FOLFOX4 | 12.9 | 31.1 | 56/87 (64.4%) |
| FOLFOX4 | 9.9 | 24.0 | 41/83 (49.4%) |
| HR (95% CI) | 0.68 (0.49-0.94) | 0.62 (0.44-0.88) | |
CI = confidence intervals
Conclusions
Although the definition of tumour-related symptoms used in this study has some limitations, this exploratory analysis suggests that first-line pmab + FOLFOX4 treatment significantly improves PFS and OS vs FOLFOX4 alone in pts with RAS WT/BRAF WT mCRC who are candidates for disease control.
Clinical trial identification
NCT00364013
Legal entity responsible for the study
Amgen
Funding
Amgen (Europe) GmbH
Disclosure
J. Taieb: Honoraria/consulting/advisory role for Roche, Amgen, Merck, Lilly, Sanofi, Celgene, Sirtex. M. Peeters: Received research funding and acted in consultancy/advisory roles for Amgen and received research funding and participated in symposia for Merck Serono. S. Siena: Member of advisory boards or steering committees or principal investigator for Amgen, Bayer, Boehringer Ingelheim, Celgene, Genentech, Ignyta, Merck, Merrimack, Novartis, Pfizer, Roche and Sanofi Aventis. F. Rivera Herrero: Acted on advisory boards and received research funding from Amgen, Sanofi, Merck-Serono and Roche. R. Koukakis: Amgen Ltd employee and stockholder. G. Demonty: Amgen (Europe) GmbH employee and stockholder. J-Y. Douillard: Honoraria/consulting/advisory roles for Amgen, Bayer, Roche, Merck; Research funding from Merck Serono; Travel/accommodation/expenses from Amgen, Bayer, Roche, Merck.