Abstract 433P
Background
Single agent PD-1/PD-L1 inhibition is not effective in metastatic colorectal cancer (MCRC) with microsatellite stable tumors. Signal of efficacy was shown using anti-PD-L1 and anti CTLA-4 in multitreated patients. FOLFOX regimen could induced immunogenic cell death, leading to a potential positive effect on antitumor immune response.
Methods
The aim of single arm phase II MEDITREME trial was to evaluate efficacy and safety of mFOLFOX6 (6 cycles) in combination with durvalumab (750mg/q2W) and tremelimumab (75mg/q4W) as induction therapy followed by maintenance therapy with durvalumab in patients with previously untreated RAS-mutated MCRC. Primary endpoint was 6 months progression-free survival (PFS) rate. Secondary endpoints included overall response rate (ORR), disease control rate (DCR), overall survival, safety and translational research. We present the results for the first year of follow-up.
Results
Overall 57 pts were enrolled. Median age was 63.6 (range 28-80), 33 pts (58%) were female. 30 pts (52%) had left- colon or rectal cancer. 45 pts (79%) had liver metastases. 11 pts (19%) received FOLFOX as adjuvant therapy. 53 pts (93%) had K-RAS and 4 pts (7%) N-RAS mutations. 3 pts (5%) were MSI-H. Treatment-related Gr 3-4 AEs occurred in 75%, of patients. Most frequent Gr 3-4 AEs were gastrointestinal and haematological mainly related to chemotherapy and occured during induction period. ORR and DCR were 61% and 89%, respectively, including 7 complete responses (12%), 29 partial responses (51%), 15 stable diseases (26%). 5 pts (9%) had progression and 1 was not evaluable. Median PFS was 8.4 months [95% CI:6-NR].6 months PFS was 63.2% [95% CI: 49-74%] and 12 months PFS was 39% [95% CI: 26-51%]. High baseline levels of Th2 and PDL1+ MDSC were associated with poor PFS. Updated translational data will be presented at the meeting.
Conclusions
This analysis supported safety of the regimen. The combination showed PFS rates similar to PFS rates with chemotherapy doublet plus target therapies but with the advantage of only 3 months of chemotherapy. Translational data are being analysed to identify which patients could benefit from such therapy.
Clinical trial identification
NCT03202758.
Editorial acknowledgement
Legal entity responsible for the study
Centre Georges Francois Leclerc.
Funding
AstraZeneca.
Disclosure
J. Fumet: Financial Interests, Personal, Research Grant: Tessaro; Financial Interests, Personal, Invited Speaker: Astra; BMS; MSD.B. Chibaudel: Financial Interests, Personal, Invited Speaker: Sanofi; Astra; Amgen; Merck; BMS.J. Bennouna: Financial Interests, Personal, Invited Speaker: Astra; MSD; BMS; Sanofi; Merck; Amgen. C. Borg: Financial Interests, Personal, Invited Speaker: BMS; MSD; Astra; Sanofi; Roche. J. Taieb: Financial Interests, Personal, Invited Speaker: Amgen; MSD; BMS; Merck; Roche; Astra; Sanofi. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen; Sanofi; Merck; MSD; BMS. All other authors have declared no conflicts of interest.