Abstract 396P
Background
Depth of response (DpR) is associated with improved progression-free survival (PFS) and overall survival (OS) in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). There are limited data on the relevance of DpR to induction therapy for consecutive maintenance treatment. Thus, the impact of DpR to induction with 6 cycles of 5-fluoruracil/leucovorin (FU/FA), oxaliplatin and panitumumab (pmab) on the efficacy of maintenance therapy with pmab-FU/FA vs. FU/FA alone was examined within the randomized PanaMa trial.
Methods
Computed tomography and magnetic resonance imaging were used for central radiologic assessment. DpR was defined as change of tumor diameter from baseline 1 (pre-induction) to baseline 2 (post-induction). Cox regression models and log-rank tests estimated hazard ratios including 95% confidence intervals of DpR (grouped as DpR 1= <0-30%; DpR 2= >30-50%; DpR 3= >50-100%) on PFS and OS during maintenance therapy.
Results
Out of 248 patients in the full analysis set 211 were evaluable for central review and DpR analysis (arm A, n=106; arm B, n=105). Median DpR was similar in both treatment arms (42.7% [arm A] vs. 42.2% [arm B]). Cox regression analysis demonstrated a significant correlation of initial DpR with both consecutive PFS (p=0.023) and OS (p=0.046) in the pmab-arm while in patients receiving FU/FA alone this association was not observed. There was no predictive value of DpR groups on efficacy according to treatment arm. Table: 396P
| FU/FA+pmab (n=106) | FU/FA (n=105) | |||||
| DpR 1 <0-30% | DpR 2 >30-50% | DpR 3 >50-100% | DpR 1 <0-30% | DpR 2 >30-50% | DpR 3 >50-100% | |
| Patients (n) | 21 | 52 | 33 | 20 | 52 | 33 |
| Median PFS, months (95% CI) | 8.1 (2.7-13.5) | 9.9 (6.8-13.1) | 9.5 (5.5-13.5) | 5.2 (4.6-5.8) | 5.8 (4.9-6.7) | 6.1 (4.2-8.1) |
| HR (95% CI), p (log-rank) | - | 0.57 (0.35-1.02) | 0.43 (0.24-0.80) | - | 0.69 (0.40-1.18) | 0.60 (0.33-1.08) |
| p=0.023 | p=0.213 | |||||
| Median OS, months (95% CI) | 16.4 (12.2-20.6) | 28.2 (23.9-32.5) | 27.4 (21.1-33.8) | 17.1 (14.9-19.4) | 26.4 (22.4-30.5) | 28.1 (22.9-33.4) |
| HR (95% CI), p (log-rank) | - | 0.50 (0.26-0.94) | 0.46 (0.23-0.92) | - | 0.52 (0.26-1.303) | 0.40 (0.18-0.87) |
| p=0.046 | p=0.054 |
Conclusions
In RAS WT mCRC treated within in the PanaMa trial, DpR to induction therapy has a prognostic impact on subsequent maintenance treatment. This effect appears pronounced in patients receiving pmab-based maintenance therapy.
Clinical trial identification
NCT01991873, first posted November 25, 2013.
Editorial acknowledgement
Legal entity responsible for the study
AIO-Studien-gGmbH.
Funding
Amgen.
Disclosure
A. Kurreck: Financial Interests, Personal, Other, Travel, accomodation: Amgen. M. Karthaus: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen. L. Fischer von Weikersthal: Financial Interests, Personal, Invited Speaker: Lilly, Novartis, Pierre-Fabre. A. Stahler: Financial Interests, Personal, Invited Speaker: Roche, Taiho Pharmaceutical, Servier; Financial Interests, Personal, Other, Travel & accomodations: Roche, Merck KGaA, Amgen, Pfizer, Lilly Oncology. V. Heinemann: Financial Interests, Personal, Advisory Board: Merck, Amgen, Roche, Sanofi, SIRTEX, Sevrier, Pfizer, Pierre-Fabre, Astra-Zeneca, BMS, MSD, Novartis, Boehringer-Ingelheim, Celgene, Terumo, Oncosil, Seagen; Financial Interests, Institutional, Research Grant: Merck, Amgen, Roche, Sanofi, Boehringer-Ingelheim, SIRTEX, Servier. A.H.S. Alig: Financial Interests, Personal, Advisory Role: MSD. S. Stintzing: Financial Interests, Personal, Advisory Board: Amgen, Bayer, Lilly, Pierre_Fabre, Merck KgaA, MSD, Roche, Sanofi, Taiho, Takeda; Financial Interests, Personal, Invited Speaker: Leo Pharma; Financial Interests, Institutional, Research Grant: Merck KGaA, Pierre-Fabre, Roche. T. Trarbach: Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Personal, Invited Speaker: Ipsen; Financial Interests, Personal, Other: Takeda, OMT, AbbVie, Novartis, MSD, Sanofi/Aventis, Amgen, Johnson & Johnson / Janssen. D.P. Modest: Financial Interests, Personal, Invited Speaker: Amgen, Merck, Servier, Pierre-Fabre, BMS, MSD, Incyte, Lilly, Sanofi, G1, Transgene, Seagan, Onkowissen; Financial Interests, Institutional, Research Grant: Servier, Amgen. All other authors have declared no conflicts of interest.